FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bhuiyan, MS Abu Sayeed, M Khanam, F Leung, DT Bhuiyan, TR Sheikh, A Salma, U LaRocque, RC Harris, JB Pacek, M Calderwood, SB LaBaer, J Ryan, ET Qadri, F Charles, RC AF Bhuiyan, Md Saruar Abu Sayeed, Md Khanam, Farhana Leung, Daniel T. Bhuiyan, Taufiqur Rahman Sheikh, Alaullah Salma, Umme LaRocque, Regina C. Harris, Jason B. Pacek, Marcin Calderwood, Stephen B. LaBaer, Joshua Ryan, Edward T. Qadri, Firdausi Charles, Richelle C. TI Cellular and Cytokine Responses to Salmonella enterica Serotype Typhi Proteins in Patients with Typhoid Fever in Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID VIBRIO-CHOLERAE O1; SEROVAR TYPHI; IFN-GAMMA; TRANSCUTANEOUS IMMUNIZATION; PROTECTIVE IMMUNITY; BACTERIAL CLEARANCE; PERIPHERAL-BLOOD; TYPHIMURIUM; MICE; INFECTION AB We assessed interferon-gamma (IFN-gamma) responses via enzyme-linked immunosorbent spot (ELISPOT) to a number of S. Typhi antigens in samples from humans with S. Typhi bacteremia and typhoid fever in Bangladesh. Compared with responses in healthy endemic zone controls, there were significantly increased IFN-gamma responses at the time of clinical presentation (acute phase) and at convalescence 14-28 days later. The majority (80-90%) of IFN-gamma expressing T cells were CD4+. We observed a significant increase in interleukin-17 (IL-17) positive CD4 + T cells at convalescent versus acute stage of infection using an intracellular cytokine staining assay. We also found that stimulated peripheral blood mononuclear cells (PBMCs) produced significantly increased levels of a number Of cytokines at the convalescent versus acute phase of infection, including IFN-gamma, MIP-1 beta, sCD40L, TNF-beta, IL-13, and IL-9. These results suggest that S. Typhi antigens induce a predominantly Th1 response, but that elevations in other cytokines may be modulatory. C1 Int Ctr Diarrhoeal Dis Res, Div Vaccine Sci, Dhaka, Bangladesh. [LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.; Charles, Richelle C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Pacek, Marcin; LaBaer, Joshua] Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Charles, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM saruar-bhuiyan@monash.edu; sabuj_11@yahoo.com; farhanak@icddrb.org; dleung@partners.org; taufiqur@icddrb.org; alaullahsheikh@yahoo.com; nayan_bmb2008@yahoo.com; rclarocque@partners.org; jbharris@partners.org; marcin.pacek@ikerlan.es; scalderwood@partners.org; joshua.labaer@asu.edu; etryan@partners.org; fqadri@icddrb.org; recharles@partners.org OI leung, daniel/0000-0001-8401-0801 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [AI100023, AI077883, AI058935]; Fogarty International Center [TW005572, R24 TW007988]; Howard Hughes Medical Institute; Massachusetts General Hospital Physician Scientist Development Award; Burroughs Welcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases; [HHSN266200400053C/N01-A1-40053]; [K01 TW07409]; [K01 TW07144]; [K08 AI089721]; [K08 AI100923] FX This work was supported by the icddr,b and grants and contracts from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (AI100023 and AI077883 [E.T.R., F.Q.]; AI058935 [S.B.C, E.T.R., and F.Q.]; contract HHSN266200400053C/N01-A1-40053 [M.P. and LLD, Training Grant in Vaccine Development and Public Health (TW005572 [M.S.B., F.K., A.S., and F.Q.]), Career Development Awards (K01 TW07409 [J.B.H.], K01 TW07144 [R.C.L.]. K08 AI089721 [R.C.C.], K08 AI100923 [D.T.L.]), an American Recovery and Reinvestment Act (ARRA) Post-doctoral Fellowship in Global Infectious Diseases (TW005572 [D.T.L., R.C.C.]), a Clinical Research Scholars Award (R24 TW007988 [S.B.C.]) from the Fogarty International Center, a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (R.C.L.), a Massachusetts General Hospital Physician Scientist Development Award (R.C.C.), and a Burroughs Welcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship in Tropical Infectious Diseases (D.T.L.). NR 34 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 EI 1476-1645 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUN PY 2014 VL 90 IS 6 BP 1024 EP 1030 DI 10.4269/ajtmh.13-0261 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA AI4FD UT WOS:000336820200009 ER PT J AU Heathcote, GM Bromage, TG Sava, VJ Hanson, DB Anderson, BE AF Heathcote, Gary M. Bromage, Timothy G. Sava, Vincent J. Hanson, Douglas B. Anderson, Bruce E. TI Enigmatic Cranial Superstructures Among Chamorro Ancestors From the Mariana Islands: Gross Anatomy and Microanatomy SO ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY LA English DT Article DE Chamorros; occipital torus tubercle; retromastoid process; posterior supramastoid tubercle; entheses; functional anatomy; SEM survey ID MUSCULOSKELETAL STRESS MARKERS; STANDARDIZED SCORING METHOD; TENDON ENTHESES; BONE; OSTEOBIOGRAPHY; ATTACHMENT; HISTOLOGY; PROPOSAL; ORIGINS; MUSCLES AB This study focuses on the gross anatomy, anatomic relations, micro-anatomy, and the meaning of three enigmatic, geographically patterned, and quasi-continuous superstructures of the posterior cranium. Collectively known as occipital superstructures (OSSs), these traits are the occipital torus tubercle (TOT), retromastoid process (PR), and posterior supramastoid tubercle (TSP). When present, TOT, PR, and TSP develop at posterior cranial attachment sites of the upper trapezius, superior oblique, and sternocleidomastoid muscles, respectively. Marked expression and co-occurrence of these OSSs are virtually circumscribed within Oceania and reach highest recorded frequencies in protohistoric Chamorros (CHamoru) of the Mariana Islands. Prior to undertaking scanning electron microscopy (SEM) work, our working multifactorial model for OSS development was that early-onset, long-term, and chronic activity-related microtrauma at enthesis sites led to exuberant reactive or reparative responses in a substantial minority of genetically predisposed (and mostly male) individuals. SEM imaging, however, reveals topographic patterning that questions, but does not negate, activity induction of these superstructures. Although OSSs appear macroscopically as relatively large and discrete phenomena, SEM findings reveal a unique, widespread, and seemingly systemic distribution of structures over the occipital surface that have the appearance of OSS microforms. Nevertheless, apparent genetic underpinnings, anatomic relationships with muscle entheses, and positive correlation of OSS development with humeral robusticity continue to suggest that these superstructures have potential to at once bear witness to Chamorro population history and inform osteobiographical constructions of chronic activity patterns in individuals bearing them. Further work is outlined that would illuminate the proximate and ultimate meanings of OSS. (C) 2014 Wiley Periodicals, Inc. C1 [Heathcote, Gary M.] St Thomas Univ, Dept Anthropol, Fredericton, NB E3B 5G3, Canada. [Bromage, Timothy G.] NYU, Coll Dent, Hard Tissue Res Unit, Dept Biomat & Biomimet, New York, NY USA. [Bromage, Timothy G.] NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, New York, NY USA. [Sava, Vincent J.] Joint Base Pearl Harbor Hickam, JPAC Cent Identificat Lab, Honolulu, HI USA. [Hanson, Douglas B.] Forsyth Inst, Cambridge, MA USA. [Anderson, Bruce E.] Univ Arizona, Sch Anthropol, Tucson, AZ USA. RP Heathcote, GM (reprint author), St Thomas Univ, Dept Anthropol, Fredericton, NB E3B 5G3, Canada. EM zinjman@gmail.com OI Heathcote, Gary/0000-0002-4384-0670 FU NSF; Max Planck; NIEHS; College of Liberal Arts and Social Sciences, University of Guam FX Grant sponsors: NSF and Max Planck (T.G.B.); NIEHS (D.B.H.); College of Liberal Arts and Social Sciences, University of Guam (G.M.H.). NR 101 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-8486 EI 1932-8494 J9 ANAT REC JI Anat. Rec. PD JUN PY 2014 VL 297 IS 6 BP 1009 EP 1021 DI 10.1002/ar.22920 PG 13 WC Anatomy & Morphology SC Anatomy & Morphology GA AI7DJ UT WOS:000337042100003 PM 24753475 ER PT J AU Genkinger, JM Wang, M Li, R Albanes, D Anderson, KE Bernstein, L van den Brandt, PA English, DR Freudenheim, JL Fuchs, CS Gapstur, SM Giles, GG Goldbohm, RA Hakansson, N Horn-Ross, PL Koushik, A Marshall, JR McCullough, ML Miller, AB Robien, K Rohan, TE Schairer, C Silverman, DT Stolzenberg-Solomon, RZ Virtamo, J Willett, WC Wolk, A Ziegler, RG Smith-Warner, SA AF Genkinger, J. M. Wang, M. Li, R. Albanes, D. Anderson, K. E. Bernstein, L. van den Brandt, P. A. English, D. R. Freudenheim, J. L. Fuchs, C. S. Gapstur, S. M. Giles, G. G. Goldbohm, R. A. Hakansson, N. Horn-Ross, P. L. Koushik, A. Marshall, J. R. McCullough, M. L. Miller, A. B. Robien, K. Rohan, T. E. Schairer, C. Silverman, D. T. Stolzenberg-Solomon, R. Z. Virtamo, J. Willett, W. C. Wolk, A. Ziegler, R. G. Smith-Warner, S. A. TI Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies SO ANNALS OF ONCOLOGY LA English DT Review DE pancreatic cancer; dairy products; calcium intake; pooled analysis ID FOOD-FREQUENCY QUESTIONNAIRE; VITAMIN-D STATUS; DIETARY ASSESSMENT; UNITED-STATES; REGRESSION-MODELS; MALE SMOKERS; CALIFORNIA TEACHERS; 25-HYDROXYVITAMIN D; NUTRITIONAL FACTORS; EXOCRINE PANCREAS AB .Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing a parts per thousand yen500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes a parts per thousand yen1300 with < 500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk. C1 [Genkinger, J. M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Wang, M.; Li, R.; Willett, W. C.; Smith-Warner, S. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wang, M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Albanes, D.; Schairer, C.; Silverman, D. T.; Stolzenberg-Solomon, R. Z.; Ziegler, R. G.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Anderson, K. E.] Univ Minnesota, Sch Publ Hlth, Mason Canc Ctr, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Bernstein, L.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA 91010 USA. [Bernstein, L.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [van den Brandt, P. A.] Maastricht Univ, Sch Oncol & Dev Biol GROW, Dept Epidemiol, Maastricht, Netherlands. [English, D. R.; Giles, G. G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Canc Epidemiol Ctr,Canc Council Victoria, Melbourne, Vic, Australia. [Freudenheim, J. L.; Marshall, J. R.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. [Fuchs, C. S.] Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Fuchs, C. S.; Willett, W. C.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Fuchs, C. S.; Willett, W. C.] Harvard Univ, Sch Med, Boston, MA USA. [Gapstur, S. M.; McCullough, M. L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Goldbohm, R. A.] TNO Qual Life, Dept Prevent & Hlth, Leiden, Netherlands. [Hakansson, N.; Wolk, A.] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. [Horn-Ross, P. L.] Canc Prevent Inst Calif, Fremont, CA USA. [Koushik, A.] Univ Montreal, Dept Social & Prevent Med, Montreal, PQ, Canada. [Miller, A. B.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [Robien, K.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA. [Rohan, T. E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Virtamo, J.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Willett, W. C.; Smith-Warner, S. A.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Genkinger, JM (reprint author), Mailman Sch Publ Hlth, Dept Epidemiol, 722 W 168th St, New York, NY 10019 USA. EM jg3081@columbia.edu RI Albanes, Demetrius/B-9749-2015; OI Robien, Kim/0000-0002-2120-2280; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188 FU National Institutes of Health [CA55075, CA139578] FX This work was supported by National Institutes of Health grants #CA55075 and #CA139578. NR 87 TC 10 Z9 10 U1 3 U2 17 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 JUN PY 2014 VL 25 IS 6 BP 1106 EP 1115 DI 10.1093/annonc/mdu019 PG 10 WC Oncology SC Oncology GA AI6ZO UT WOS:000337028100005 PM 24631943 ER PT J AU Boyer-Guittaut, M Poillet, L Liang, QL Bole-Richard, E Ouyang, XS Benavides, GA Chakrama, FZ Fraichard, A Darley-Usmar, VM Despouy, G Jouvenot, M Delage-Mourroux, R Zhang, JH AF Boyer-Guittaut, Michael Poillet, Laura Liang, Qiuli Bole-Richard, Elodie Ouyang, Xiaosen Benavides, Gloria A. Chakrama, Fatima-Zahra Fraichard, Annick Darley-Usmar, Victor M. Despouy, Gilles Jouvenot, Michele Delage-Mourroux, Regis Zhang, Jianhua TI The role of GABARAPL1/GEC1 in autophagic flux and mitochondrial quality control in MDA-MB-436 breast cancer cells SO AUTOPHAGY LA English DT Article DE autophagy; breast cancer; GABARAP; GABARAPL1; GEC1; LAMP1; LC3; lysosome; MDA-MB-436; mitochondria; mitophagy ID CENTRAL-NERVOUS-SYSTEM; OXIDATIVE STRESS; PARKINSONS-DISEASE; MESSENGER-RNAS; GLYCOGEN-METABOLISM; GABA(A) RECEPTOR; GENE-EXPRESSION; SMOKE EXPOSURE; PROTEIN; GEC1 AB GABARAPL1/GEC1 is an early estrogen-induced gene which encodes a protein highly conserved from C. elegans to humans. Overexpressed GABARAPL1 interacts with GABA A or kappa opioid receptors, associates with autophagic vesicles, and inhibits breast cancer cell proliferation. However, the function of endogenous GABARAPL1 has not been extensively studied. We hypothesized that GABARAPL1 is required for maintaining normal autophagic flux, and plays an important role in regulating cellular bioenergetics and metabolism. To test this hypothesis, we knocked down GABARAPL1 expression in the breast cancer MDA-MB-436 cell line by shRNA. Decreased expression of GABARAPL1 activated procancer responses of the MDA-MB-436 cells including increased proliferation, colony formation, and invasion. In addition, cells with decreased expression of GABARAPL1 exhibited attenuated autophagic flux and a decreased number of lysosomes. Moreover, decreased GABARAPL1 expression led to cellular bioenergetic changes including increased basal oxygen consumption rate, increased intracellular ATP, increased total glutathione, and an accumulation of damaged mitochondria. Taken together, our results demonstrate that GABARAPL1 plays an important role in cell proliferation, invasion, and autophagic flux, as well as in mitochondrial homeostasis and cellular metabolic programs. C1 [Boyer-Guittaut, Michael; Poillet, Laura; Bole-Richard, Elodie; Chakrama, Fatima-Zahra; Fraichard, Annick; Despouy, Gilles; Jouvenot, Michele; Delage-Mourroux, Regis] Univ Franche Comte, Lab Biochim, Estrogenes Express Genique & Pathol Syst Nerveux, F-25030 Besancon, France. [Boyer-Guittaut, Michael; Liang, Qiuli; Ouyang, Xiaosen; Benavides, Gloria A.; Darley-Usmar, Victor M.; Zhang, Jianhua] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Boyer-Guittaut, Michael; Liang, Qiuli; Ouyang, Xiaosen; Benavides, Gloria A.; Darley-Usmar, Victor M.; Zhang, Jianhua] Univ Alabama Birmingham, Ctr Free Rad Biol, Birmingham, AL USA. [Ouyang, Xiaosen; Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL USA. RP Zhang, JH (reprint author), Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. EM michael.boyer-guittaut@univ-fcomte.fr; zhanja@uab.edu OI Zhang, Jianhua/0000-0002-2128-9574 FU Universite of Franche-Comte; Region de Franche-Comte; VA merit award; RDCC-APCC core (NIH P30 grant) [P30 AR48311]; [NIHR01-NS064090] FX Michael Boyer-Guittaut would like to thank his colleagues from the EA3922 team, Jacques Bahi, president of the Universite of Franche-Comte, Abderrazzak Kadmiri, director of UFR-ST of the Universite of Franche-Comte and the Universite of Franche-Comte for their support during this research project performed at the University of Alabama in Birmingham, AL, USA. Laura Poillet is supported by a fellowship of the Region de Franche-Comte. The authors acknowledge funding from the following sources: Dr Jianhua Zhang was supported by NIHR01-NS064090 and a VA merit award. Flow cytometry was supported by RDCC-APCC core (NIH P30 grant #P30 AR48311). The authors would like to thank Enid F Keyser (UAB Flow cytometry core, Birmingham, AL) for her technical help using the LSR-II Becton Dickinson flow cytometer. Authors are grateful to Jianhua Zhang's and Victor M Darley-Usmar's laboratory members for their technical help, advice, and critical reviewing of this manuscript. NR 64 TC 14 Z9 14 U1 2 U2 16 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 EI 1554-8635 J9 AUTOPHAGY JI Autophagy PD JUN PY 2014 VL 10 IS 6 BP 986 EP 1003 DI 10.4161/auto.28390 PG 18 WC Cell Biology SC Cell Biology GA AI6GT UT WOS:000336970800004 PM 24879149 ER PT J AU Marshansky, V Rubinstein, JL Gruber, G AF Marshansky, Vladimir Rubinstein, John L. Grueber, Gerhard TI Eukaryotic V-ATPase: Novel structural findings and functional insights SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Review DE Eukaryotic V-ATPase; Rotary proton-pumping nano-motor; Trafficking via endocytotic and exocytotic pathways; Regulation of cellular receptors function; Cytohesin-2/Arfs signaling; pH sensor ID VACUOLAR H+-ATPASE; PROTON-TRANSLOCATING ATPASE; CLATHRIN-INDEPENDENT ENDOCYTOSIS; IN-VIVO DISSOCIATION; BREAST-CANCER CELLS; NUCLEOTIDE EXCHANGE FACTORS; CLC CHLORIDE TRANSPORTERS; RENAL TUBULAR-ACIDOSIS; SUBUNIT-C VMA5P; ELECTRON-MICROSCOPY AB The eukaryotic V-type adenosine triphosphatase (V-ATPase) is a multi-subunit membrane protein complex that is evolutionarily related to F-type adenosine triphosphate (ATP) synthases and A-ATP synthases. These ATPases/ATP synthases are functionally conserved and operate as rotary proton-pumping nano-motors, invented by Nature billions of years ago. In the first part of this review we will focus on recent structural findings of eukaryotic V-ATPases and discuss the role of different subunits in the function of the V-ATPase holocomplex. Despite structural and functional similarities between rotary ATPases, the eukaryotic V-ATPases are the most complex enzymes that have acquired some unconventional cellular functions during evolution. In particular, the novel roles of V-ATPases in the regulation of cellular receptors and their trafficking via endocytodc and exocytotic pathways were recently uncovered. In the second part of this review we will discuss these unique roles of V-ATPases in modulation of function of cellular receptors, involved in the development and progression of diseases such as cancer and diabetes as well as neurodegeneradve and kidney disorders. Moreover, it was recently revealed that the V-ATPase itself functions as an evolutionarily conserved pH sensor and receptor for cytohesin-2/Arf-family GTP-binding proteins. Thus, in the third part of the review we will evaluate the structural basis for and functional insights into this novel concept, followed by the analysis of the potentially essential role of V-ATPase in the regulation of this signaling pathway in health and disease. Finally, future prospects for structural and functional studies of the eukaryotic V-ATPase will be discussed. (C) 2014 Elsevier B.V. All rights reserved. C1 [Marshansky, Vladimir] Harvard Univ, Massachusetts Gen Hosp, Ctr Syst Biol,Sch Med, Program Membrane Biol,Div Nephrol,Simches Res Ctr, Boston, MA 02114 USA. [Marshansky, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Marshansky, Vladimir] Kadmon Pharmaceut Corp, Alexandria Ctr Life Sci, New York, NY 10016 USA. [Rubinstein, John L.] Univ Toronto, Hosp Sick Children Res Inst, Mol Struct & Funct Program, Toronto, ON M5G 1X8, Canada. [Rubinstein, John L.] Univ Toronto, Dept Biochem, Toronto, ON M5G 1X8, Canada. [Rubinstein, John L.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1X8, Canada. [Grueber, Gerhard] Nanyang Technol Univ, Div Struct Biol & Biochem, Sch Biol Sci, Singapore 637551, Singapore. [Grueber, Gerhard] ASTAR, Bioinformat Inst, Singapore 637551, Singapore. RP Marshansky, V (reprint author), Massachusetts Gen Hosp, Simches Res Ctr, Div Nephrol, Ctr Syst Biol,Program Membrane Biol, Boston, MA 02114 USA. EM Vladimir_Marshansky@hms.harvard.edu OI Rubinstein, John/0000-0003-0566-2209 FU NIH [DK038452]; BADERC [DK057521-08]; A*STAR BMRC [09/1/22/19/609]; Ministry of Education Tier 2, Singapore [MOE2011-T22-156, ARC 18/12]; CIHR [MOP81294] FX Original work in the authors' laboratories is supported by NIH DK038452, BADERC DK057521-08 (Marshansky) as well as by A*STAR BMRC, 09/1/22/19/609, Ministry of Education Tier 2 (MOE2011-T22-156; ARC 18/12), Singapore (Gruber) and by CIHR MOP81294 (Rubinstein). We thank Dr. S. S. M. Malathy (School of Biological Sciences, NTU) for the art work of the Figs. 2-4. NR 266 TC 49 Z9 54 U1 7 U2 36 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 EI 0006-3002 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD JUN PY 2014 VL 1837 IS 6 BP 857 EP 879 DI 10.1016/j.bbabio.2014.01.018 PG 23 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA AI6UW UT WOS:000337013500016 PM 24508215 ER PT J AU Halper-Stromberg, E Steranka, J Burns, KH Sabunciyan, S Irizarry, RA AF Halper-Stromberg, Eitan Steranka, Jared Burns, Kathleen H. Sabunciyan, Sarven Irizarry, Rafael A. TI Visualization and probability-based scoring of structural variants within repetitive sequences SO BIOINFORMATICS LA English DT Article ID COPY-NUMBER; READ ALIGNMENT; HUMAN GENOME; DNA; QUALITY; MODEL AB Motivation: Repetitive sequences account for approximately half of the human genome. Accurately ascertaining sequences in these regions with next generation sequencers is challenging, and requires a different set of analytical techniques than for reads originating from unique sequences. Complicating the matter are repetitive regions subject to programmed rearrangements, as is the case with the antigen-binding domains in the Immunoglobulin (Ig) and T-cell receptor (TCR) loci. Results: We developed a probability-based score and visualization method to aid in distinguishing true structural variants from alignment artifacts. We demonstrate the usefulness of this method in its ability to separate real structural variants from false positives generated with existing upstream analysis tools. We validated our approach using both target-capture and whole-genome experiments. Capture sequencing reads were generated from primary lymphoid tumors, cancer cell lines and an EBV-transformed lymphoblast cell line over the Ig and TCR loci. Whole-genome sequencing reads were from a lymphoblastoid cell-line. C1 [Halper-Stromberg, Eitan; Irizarry, Rafael A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21218 USA. [Halper-Stromberg, Eitan] Johns Hopkins Univ, Sch Med, Program Human Genet & Mol Biol, Baltimore, MD 21218 USA. [Halper-Stromberg, Eitan] Univ Colorado, Computat Biosci Program, Denver, CO 80202 USA. [Steranka, Jared] Johns Hopkins Univ Hosp, Dept Mol Biol & Genet, Baltimore, MD 21287 USA. [Burns, Kathleen H.] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21287 USA. [Burns, Kathleen H.] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. [Burns, Kathleen H.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Burns, Kathleen H.] Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, Baltimore, MD USA. [Sabunciyan, Sarven] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA. [Sabunciyan, Sarven] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Irizarry, Rafael A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Halper-Stromberg, E (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21218 USA. EM ehalper2@jhmi.edu FU National Institutes of Health [R01HG005220] FX The National Institutes of Health (R01HG005220). NR 31 TC 2 Z9 2 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD JUN 1 PY 2014 VL 30 IS 11 BP 1514 EP 1521 DI 10.1093/bioinformatics/btu054 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA AI7CU UT WOS:000337040200004 PM 24501098 ER PT J AU Maeda, Y Kettner, N Holden, J Lee, J Kim, J Cina, S Malatesta, C Gerber, J McManus, C Im, J Libby, A Mezzacappa, P Morse, LR Park, K Audette, J Tommerdahl, M Napadow, V AF Maeda, Yumi Kettner, Norman Holden, Jameson Lee, Jeungchan Kim, Jieun Cina, Stephen Malatesta, Cristina Gerber, Jessica McManus, Claire Im, Jaehyun Libby, Alexandra Mezzacappa, Pia Morse, Leslie R. Park, Kyungmo Audette, Joseph Tommerdahl, Mark Napadow, Vitaly TI Functional deficits in carpal tunnel syndrome reflect reorganization of primary somatosensory cortex SO BRAIN LA English DT Article DE functional magnetic resonance imaging (fMRI); median nerve neuropathy; tactile stimulation; psychomotor performance; finger agnosia ID TACTILE STIMULATION; SENSORY INFORMATION; ADULT MONKEYS; CORTICAL MAP; HAND; PAIN; CAPACITY; BACK; MISLOCALIZATION; DEAFFERENTATION AB The functional significance of brain plasticity seen in carpal tunnel syndrome is unclear. Using functional MRI and bio-behavioural testing, Maeda et al. link blurred primary somatosensory cortical representations of median nerve innervated fingers with symptomatology and impaired psychomotor performance and discrimination accuracy. Neuroplasticity in these patients is thus indeed maladaptive.Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits. Recent reports have shown that this syndrome is also characterized by functional and structural neuroplasticity in the primary somatosensory cortex of the brain. However, the linkage between this neuroplasticity and the functional deficits in carpal tunnel syndrome is unknown. Sixty-three subjects with carpal tunnel syndrome aged 20-60 years and 28 age- and sex-matched healthy control subjects were evaluated with event-related functional magnetic resonance imaging at 3 T while vibrotactile stimulation was delivered to median nerve innervated (second and third) and ulnar nerve innervated (fifth) digits. For each subject, the interdigit cortical separation distance for each digit's contralateral primary somatosensory cortex representation was assessed. We also evaluated fine motor skill performance using a previously validated psychomotor performance test (maximum voluntary contraction and visuomotor pinch/release testing) and tactile discrimination capacity using a four-finger forced choice response test. These biobehavioural and clinical metrics were evaluated and correlated with the second/third interdigit cortical separation distance. Compared with healthy control subjects, subjects with carpal tunnel syndrome demonstrated reduced second/third interdigit cortical separation distance (P < 0.05) in contralateral primary somatosensory cortex, corroborating our previous preliminary multi-modal neuroimaging findings. For psychomotor performance testing, subjects with carpal tunnel syndrome demonstrated reduced maximum voluntary contraction pinch strength (P < 0.01) and a reduced number of pinch/release cycles per second (P < 0.05). Additionally, for four-finger forced-choice testing, subjects with carpal tunnel syndrome demonstrated greater response time (P < 0.05), and reduced sensory discrimination accuracy (P < 0.001) for median nerve, but not ulnar nerve, innervated digits. Moreover, the second/third interdigit cortical separation distance was negatively correlated with paraesthesia severity (r = -0.31, P < 0.05), and number of pinch/release cycles (r = -0.31, P < 0.05), and positively correlated with the second and third digit sensory discrimination accuracy (r = 0.50, P < 0.05). Therefore, reduced second/third interdigit cortical separation distance in contralateral primary somatosensory cortex was associated with worse symptomatology (particularly paraesthesia), reduced fine motor skill performance, and worse sensory discrimination accuracy for median nerve innervated digits. In conclusion, primary somatosensory cortex neuroplasticity for median nerve innervated digits in carpal tunnel syndrome is indeed maladaptive and underlies the functional deficits seen in these patients. C1 [Maeda, Yumi; Kim, Jieun; Cina, Stephen; Gerber, Jessica; Im, Jaehyun; Libby, Alexandra; Mezzacappa, Pia; Napadow, Vitaly] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Maeda, Yumi; Kettner, Norman; Napadow, Vitaly] Logan Univ, Dept Radiol, Chesterfield, MO 63017 USA. [Holden, Jameson; Tommerdahl, Mark] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USA. [Lee, Jeungchan; Park, Kyungmo; Napadow, Vitaly] Kyung Hee Univ, Dept Biomed Engn, Yongin 446701, South Korea. [Malatesta, Cristina; McManus, Claire] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Medford, MA 02155 USA. [Morse, Leslie R.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Audette, Joseph] Atrium Hlth, Harvard Vanguard Med Associates, Dept Pain Med, Boston, MA 02215 USA. RP Maeda, Y (reprint author), 2301 149 Thirteenth St, Charlestown, MA 02129 USA. EM ymaeda@nmr.mgh.harvard.edu RI Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health [R01-AT004714, R01-AT004714-02S1, P01-AT002048]; National Centre for Research Resources (NCRR) [P41RR14075, S10RR021110] FX This work was supported by National Center for Complementary and Alternative Medicine (NCCAM), National Institutes of Health [R01-AT004714, R01-AT004714-02S1, P01-AT002048], as well as the National Centre for Research Resources (NCRR) [P41RR14075, S10RR021110]. NR 53 TC 10 Z9 10 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD JUN PY 2014 VL 137 BP 1741 EP 1752 DI 10.1093/brain/awu096 PN 6 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AI6ZU UT WOS:000337028900021 PM 24740988 ER PT J AU DeGutis, J Cohan, S Nakayama, K AF DeGutis, Joseph Cohan, Sarah Nakayama, Ken TI Holistic face training enhances face processing in developmental prosopagnosia SO BRAIN LA English DT Article DE developmental prosopagnosia; computer-based cognitive remediation; configural/holistic processing ID CONGENITAL PROSOPAGNOSIA; ACQUIRED PROSOPAGNOSIA; RECOGNITION ABILITY; INDIVIDUAL FACES; TEMPORAL CORTEX; MEMORY TEST; PERCEPTION; REVEALS; AUTISM; DIFFICULTIES AB Recent case studies suggest that face recognition can be improved in individual developmental prosopagnosics. Using a 3-week online program targeting holistic face processing, DeGutis et al. reveal perceptual improvements in 24 subjects. Those who reached more difficult levels of training showed the greatest improvements in holistic processing.Prosopagnosia has largely been regarded as an untreatable disorder. However, recent case studies using cognitive training have shown that it is possible to enhance face recognition abilities in individuals with developmental prosopagnosia. Our goal was to determine if this approach could be effective in a larger population of developmental prosopagnosics. We trained 24 developmental prosopagnosics using a 3-week online face-training program targeting holistic face processing. Twelve subjects with developmental prosopagnosia were assessed before and after training, and the other 12 were assessed before and after a waiting period, they then performed the training, and were then assessed again. The assessments included measures of front-view face discrimination, face discrimination with view-point changes, measures of holistic face processing, and a 5-day diary to quantify potential real-world improvements. Compared with the waiting period, developmental prosopagnosics showed moderate but significant overall training-related improvements on measures of front-view face discrimination. Those who reached the more difficult levels of training ('better' trainees) showed the strongest improvements in front-view face discrimination and showed significantly increased holistic face processing to the point of being similar to that of unimpaired control subjects. Despite challenges in characterizing developmental prosopagnosics' everyday face recognition and potential biases in self-report, results also showed modest but consistent self-reported diary improvements. In summary, we demonstrate that by using cognitive training that targets holistic processing, it is possible to enhance face perception across a group of developmental prosopagnosics and further suggest that those who improved the most on the training task received the greatest benefits. C1 [DeGutis, Joseph] Boston Div VA Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Jamaica Plain, MA USA. [DeGutis, Joseph; Cohan, Sarah; Nakayama, Ken] Harvard Univ, Dept Psychol, Vis Sci Lab, Cambridge, MA 02138 USA. RP DeGutis, J (reprint author), Boston VA Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Boston, MA 02130 USA. EM degutis@wjh.harvard.edu FU National Institutes of Health [5R01EY013602-07] FX We would like to acknowledge funding support from the National Institutes of Health 5R01EY013602-07 awarded to KN and JD's Veterans Affairs Career Development Award. NR 59 TC 18 Z9 18 U1 3 U2 33 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD JUN PY 2014 VL 137 BP 1781 EP 1798 DI 10.1093/brain/awu062 PN 6 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AI6ZU UT WOS:000337028900025 PM 24691394 ER PT J AU Ali, A Ku, JH Suhler, EB Choi, D Rosenbaum, JT AF Ali, Amro Ku, Jennifer H. Suhler, Eric B. Choi, Dongseok Rosenbaum, James T. TI The course of retinal vasculitis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SYSTEMIC ASSOCIATIONS; MULTIPLE-SCLEROSIS; DISEASE; CORTICOSTEROIDS; PERIPHLEBITIS; EFFICACY AB Aims To determine if characteristics of retinal vasculitis correlate with ocular complications, or the response to different lines of treatment. Materials and methods We performed a computerised database analysis of 56 patients evaluated for uveitis at the Casey Eye Institute from September 1985 until May 2010. All patients had non-infectious retinal vasculitis and at least 1 year of follow-up. Results Although occlusive vasculitis was rare, retinal neovascularisation occurred much more commonly in the occlusive vasculitis subgroup than among the nonocclusive vasculitis subgroup (p<0.01). Epiretinal membrane (ERM) was found more commonly in the retinal vasculitis patients who presented with cotton wool spots and intraretinal haemorrhage compared to retinal vasculitis patients who presented with sheathing noted on clinical examination (p<0.01). Smoking was significantly related to vision loss. Age at presentation below 40 years correlated with therapy beyond oral corticosteroids Conclusions The heterogeneity of retinal vasculitis should be considered in providing prognostic information. Neovascularisation occurs more commonly in occlusive retinal vasculitis, and ERM is diagnosed more frequently in conjunction with cotton wool spots and intraretinal haemorrhage rather than just vascular sheathing. Cigarette use predicts visual loss and patients who are relatively young often receive treatment beyond oral corticosteroids. C1 [Ali, Amro; Ku, Jennifer H.; Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97239 USA. [Ku, Jennifer H.; Suhler, Eric B.; Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Rosenbaum, James T.] Legacy Hlth Syst, Devers Eye Inst, Portland, OR USA. RP Ku, JH (reprint author), Oregon Hlth & Sci Univ, Dept Ophthalmol, Mailcode CEI,3375 Terwilliger blvd, Portland, OR 97239 USA. EM kuj@ohsu.edu FU Research to Prevent Blindness, through National Eye Institute; Stan and Madelle Rosenfeld Family Trust the William and Mary Bauman Foundation FX This work was supported by Research to Prevent Blindness, through a core grant from the National Eye Institute, and by funds from the Stan and Madelle Rosenfeld Family Trust the William and Mary Bauman Foundation. NR 26 TC 3 Z9 3 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUN PY 2014 VL 98 IS 6 BP 785 EP 789 DI 10.1136/bjophthalmol-2013-303443 PG 5 WC Ophthalmology SC Ophthalmology GA AI6JI UT WOS:000336979100017 PM 24511084 ER PT J AU Haber, DA Velculescu, VE AF Haber, Daniel A. Velculescu, Victor E. TI Blood-Based Analyses of Cancer: Circulating Tumor Cells and Circulating Tumor DNA SO CANCER DISCOVERY LA English DT Review ID RESISTANT PROSTATE-CANCER; METASTATIC BREAST-CANCER; ACQUIRED-RESISTANCE; COLORECTAL-CANCER; LUNG-CANCER; COPY NUMBER; PERIPHERAL-BLOOD; EPITHELIAL-CELLS; DIGITAL PCR; RARE CELLS AB The ability to study nonhematologic cancers through noninvasive sampling of blood is one of the most exciting and rapidly advancing fields in cancer diagnostics. This has been driven both by major technologic advances, including the isolation of intact cancer cells and the analysis of cancer cell-derived DNA from blood samples, and by the increasing application of molecularly driven therapeutics, which rely on such accurate and timely measurements of critical biomarkers. Moreover, the dramatic efficacy of these potent cancer therapies drives the selection for additional genetic changes as tumors acquire drug resistance, necessitating repeated sampling of cancer cells to adjust therapy in response to tumor evolution. Together, these advanced noninvasive diagnostic capabilities and their applications in guiding precision cancer therapies are poised to change the ways in which we select and monitor cancer treatments. Significance: Recent advances in technologies to analyze circulating tumor cells and circulating tumor DNA are setting the stage for real-time, noninvasive monitoring of cancer and providing novel insights into cancer evolution, invasion, and metastasis. C1 [Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Velculescu, Victor E.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. RP Velculescu, VE (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, 1550 Orleans St,Room 144, Baltimore, MD 21287 USA. EM haber@helix.mgh.harvard.edu; velculescu@jhmi.edu FU Howard Hughes Medical Institute; NIH [CA-129933, NIBIB-EB008047, CA-121113]; Entertainment Industry Foundation [SU2C-AACR-DT0309, SU2C-AACR-DT0509]; Breast Cancer Research Foundation; National Foundation for Cancer Research; Johnson & Johnson Center for Excellence in CTCs at Massachusetts General Hospital; European Community's Seventh Framework Programme; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; John G. Ballenger Trust; Commonwealth Foundation; Stand Up To Cancer Dream Team Translational Cancer Research Grant FX D.A. Haber is supported by the Howard Hughes Medical Institute, NIH (CA-129933, NIBIB-EB008047), a Stand Up To Cancer Dream Team Translational Cancer Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0309), the Breast Cancer Research Foundation, the National Foundation for Cancer Research, and the Johnson & Johnson Center for Excellence in CTCs at Massachusetts General Hospital. V.E. Velculescu is supported by NIH (CA-121113), The European Community's Seventh Framework Programme, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the John G. Ballenger Trust, a Stand Up To Cancer Dream Team Translational Cancer Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0509), and the Commonwealth Foundation. NR 115 TC 91 Z9 100 U1 7 U2 103 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 JUN PY 2014 VL 4 IS 6 BP 650 EP 661 DI 10.1158/2159-8290.CD-13-1014 PG 12 WC Oncology SC Oncology GA AI8QG UT WOS:000337185500022 PM 24801577 ER PT J AU Friboulet, L Li, NX Katayama, R Lee, CC Gainor, JF Crystal, AS Michellys, PY Awad, MM Yanagitani, N Kim, S Pferdekamper, AC Li, J Kasibhatla, S Sun, F Sun, XY Hua, S McNamara, P Mahmood, S Lockerman, EL Fujita, N Nishio, M Harris, JL Shaw, AT Engelman, JA AF Friboulet, Luc Li, Nanxin Katayama, Ryohei Lee, Christian C. Gainor, Justin F. Crystal, Adam S. Michellys, Pierre-Yves Awad, Mark M. Yanagitani, Noriko Kim, Sungjoon Pferdekamper, AnneMarie C. Li, Jie Kasibhatla, Shailaja Sun, Frank Sun, Xiuying Hua, Su McNamara, Peter Mahmood, Sidra Lockerman, Elizabeth L. Fujita, Naoya Nishio, Makoto Harris, Jennifer L. Shaw, Alice T. Engelman, Jeffrey A. TI The ALK Inhibitor Ceritinib Overcomes Crizotinib Resistance in Non-Small Cell Lung Cancer SO CANCER DISCOVERY LA English DT Article ID EML4-ALK FUSION GENE; KINASE INHIBITOR; MUTATIONS; NEUROBLASTOMA; EGFR AB Non-small cell lung cancers (NSCLC) harboring anaplastic lymphoma kinase (ALK) gene rearrangements invariably develop resistance to the ALK tyrosine kinase inhibitor (TKI) crizotinib. Herein, we report the first preclinical evaluation of the next-generation ALK TKI, ceritinib (LDK378), in the setting of crizotinib resistance. An interrogation of in vitro and in vivo models of acquired resistance to crizotinib, including cell lines established from biopsies of patients with crizotinib-resistant NSCLC, revealed that ceritinib potently overcomes crizotinib-resistant mutations. In particular, ceritinib effectively inhibits ALK harboring L1196M, G1269A, I1171T, and S1206Y mutations, and a cocrystal structure of ceritinib bound to ALK provides structural bases for this increased potency. However, we observed that ceritinib did not overcome two crizotinib-resistant ALK mutations, G1202R and F1174C, and one of these mutations was identified in 5 of 11 biopsies from patients with acquired resistance to ceritinib. Altogether, our results demonstrate that ceritinib can overcome crizotinib resistance, consistent with clinical data showing marked efficacy of ceritinib in patients with crizotinib-resistant disease. C1 [Friboulet, Luc; Katayama, Ryohei; Gainor, Justin F.; Crystal, Adam S.; Awad, Mark M.; Mahmood, Sidra; Lockerman, Elizabeth L.; Shaw, Alice T.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Friboulet, Luc; Katayama, Ryohei; Gainor, Justin F.; Crystal, Adam S.; Awad, Mark M.; Mahmood, Sidra; Lockerman, Elizabeth L.; Shaw, Alice T.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lee, Christian C.; Michellys, Pierre-Yves; Kim, Sungjoon; Pferdekamper, AnneMarie C.; Li, Jie; Kasibhatla, Shailaja; Sun, Frank; Sun, Xiuying; Hua, Su; McNamara, Peter; Harris, Jennifer L.] Novartis Res Fdn, Genom Inst, San Diego, CA USA. [Katayama, Ryohei; Fujita, Naoya] Japanese Fdn Canc Res, Ctr Canc Chemotherapy, Tokyo 170, Japan. [Yanagitani, Noriko; Nishio, Makoto] Japanese Fdn Canc Res, Canc Inst Hosp, Tokyo, Japan. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, CNY 149,13th St, Charlestown, MA 02129 USA. EM jharris@gnf.org; ashaw1@mgh.harvard.edu; jengelman@partners.org RI friboulet, luc/N-7276-2015 OI friboulet, luc/0000-0002-1129-4978 FU NIH [5R01CA16427302]; V Foundation Translational Research Grant; NIH/National Cancer Institute [R01CA137008]; JSPS KAKENHI [25710015] FX This work was supported by a grant from the NIH (5R01CA16427302 to A.T. Shaw and J.A. Engelman), by a V Foundation Translational Research Grant (to A.T. Shaw and J.A. Engelman) and by the NIH/National Cancer Institute (R01CA137008 to J. A. Engelman). The study was also supported by a grant from JSPS KAKENHI (25710015 to R. Katayama). NR 18 TC 210 Z9 222 U1 8 U2 55 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 JUN PY 2014 VL 4 IS 6 BP 662 EP 673 DI 10.1158/2159-8290.CD-13-0846 PG 12 WC Oncology SC Oncology GA AI8QG UT WOS:000337185500023 PM 24675041 ER PT J AU Konijeti, GG Sauk, J Shrime, MG Gupta, M Ananthakrishnan, AN AF Konijeti, Gauree G. Sauk, Jenny Shrime, Mark G. Gupta, Meera Ananthakrishnan, Ashwin N. TI Cost-effectiveness of Competing Strategies for Management of Recurrent Clostridium difficile Infection: A Decision Analysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Clostridium difficile infection; vancomycin; fidaxomicin; metronidazole; fecal microbiota transplant ID FECAL MICROBIOTA TRANSPLANTATION; QUALITY-OF-LIFE; ULCERATIVE-COLITIS; UNITED-STATES; DISEASE; HEALTH; VANCOMYCIN; FIDAXOMICIN; COLECTOMY; THERAPY AB Background. Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. Methods. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $ 50 000 per quality-adjusted life-year. Results. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $ 17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates > 88.4% and CDI recurrence rates < 14.9%. Fidaxomicin required a cost <$ 1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. Conclusions. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI. C1 [Konijeti, Gauree G.; Sauk, Jenny; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Konijeti, Gauree G.; Sauk, Jenny; Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Harvard Interfac Initiat Hlth Policy, Boston, MA USA. [Gupta, Meera] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases of the NIH [T32DK007191]; NIH [K23 DK091742] FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH (award number T32DK007191). A. N. A. is supported by the NIH (K23 DK091742). NR 44 TC 41 Z9 42 U1 3 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2014 VL 58 IS 11 BP 1507 EP 1514 DI 10.1093/cid/ciu128 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AI7AL UT WOS:000337031200004 PM 24692533 ER PT J AU Youngster, I Sauk, J Pindar, C Wilson, RG Kaplan, JL Smith, MB Alm, EJ Gevers, D Russell, GH Hohmann, EL AF Youngster, Ilan Sauk, Jenny Pindar, Christina Wilson, Robin G. Kaplan, Jess L. Smith, Mark B. Alm, Eric J. Gevers, Dirk Russell, George H. Hohmann, Elizabeth L. TI Fecal Microbiota Transplant for Relapsing Clostridium difficile Infection Using a Frozen Inoculum From Unrelated Donors: A Randomized, Open-Label, Controlled Pilot Study SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE fecal microbiota transplant; Clostridium difficile; microbiome; frozen inoculum ID VANCOMYCIN; RECURRENCE; DISEASE; METRONIDAZOLE; EPIDEMIOLOGY; OUTCOMES; CHILDREN AB Background. Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration. Methods. Healthy volunteer donors were screened and a frozen fecal suspension was generated. Patients with relapsing/refractory CDI were randomized to receive an infusion of donor stools by colonoscopy or NGT. The primary endpoint was clinical resolution of diarrhea without relapse after 8 weeks. The secondary endpoint was self-reported health score using standardized questionnaires. Results. A total of 20 patients were enrolled, 10 in each treatment arm. Patients had a median of 4 (range, 2-16) relapses prior to study enrollment, with 5 (range, 3-15) antibiotic treatment failures. Resolution of diarrhea was achieved in 14 patients (70%) after a single FMT (8 of 10 in the colonoscopy group and 6 of 10 in the NGT group). Five patients were retreated, with 4 obtaining cure, resulting in an overall cure rate of 90%. Daily number of bowel movements changed from a median of 7 (interquartile range [IQR], 5-10) the day prior to FMT to 2 (IQR, 1-2) after the infusion. Self-ranked health score improved significantly, from a median of 4 (IQR, 2-6) before transplant to 8 (IQR, 5-9) after transplant. No serious or unexpected adverse events occurred. Conclusions. In our initial feasibility study, FMT using a frozen inoculum from unrelated donors is effective in treating relapsing CDI. NGT administration appears to be as effective as colonoscopic administration. C1 [Youngster, Ilan; Pindar, Christina; Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Youngster, Ilan; Sauk, Jenny; Kaplan, Jess L.; Russell, George H.; Hohmann, Elizabeth L.] Harvard Univ, Sch Med, Boston, MA USA. [Youngster, Ilan] Boston Childrens Hosp, Div Infect Dis, Boston, MA 02445 USA. [Sauk, Jenny; Wilson, Robin G.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Kaplan, Jess L.; Russell, George H.] Massachusetts Gen Hosp Children, Dept Pediat Gastroenterol & Nutr, Boston, MA USA. [Smith, Mark B.; Alm, Eric J.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Gevers, Dirk] MIT, Broad Inst, Cambridge, MA 02139 USA. RP Youngster, I (reprint author), Boston Childrens Hosp, Div Infect Dis, 300 Longwood Ave, Boston, MA 02445 USA. EM ilan.youngster@childrens.harvard.edu RI Youngster, Ilan/J-5047-2014 OI Youngster, Ilan/0000-0001-5233-1213 FU National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services [HHSN272200900018C]; National Center for Advancing Translational Sciences, NIH [8UL1TR000170-05]; Harvard University; National Center for Research Resources FX The microbiome analysis was funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services (contract number HHSN272200900018C). I. Y. has received career support from Harvard Catalyst, The Harvard Clinical and Translational Science Center, funded by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH (award 8UL1TR000170-05), and financial contributions from Harvard University and its affiliated academic healthcare centers. NR 30 TC 110 Z9 121 U1 9 U2 66 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2014 VL 58 IS 11 BP 1515 EP 1522 DI 10.1093/cid/ciu135 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AI7AL UT WOS:000337031200005 PM 24762631 ER PT J AU Siedner, MJ Galar, A Guzman-Suarez, BB Kubiak, DW Baghdady, N Ferraro, MJ Hooper, DC O'Brien, TF Marty, FM AF Siedner, Mark J. Galar, Alicia Guzman-Suarez, Belisa B. Kubiak, David W. Baghdady, Nour Ferraro, Mary Jane Hooper, David C. O'Brien, Thomas F. Marty, Francisco M. TI Cefepime vs Other Antibacterial Agents for the Treatment of Enterobacter Species Bacteremia SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE Enterobacter; ampC; bacteremia; cefepime; comparative effectiveness ID LACTAMASE-PRODUCING ENTEROBACTERIACEAE; AMPC BETA-LACTAMASE; KLEBSIELLA-PNEUMONIAE; ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE; ANTIBIOTIC-RESISTANCE; SCORING SYSTEMS; INFECTIONS; THERAPY; CEPHALOSPORINS AB Background. Carbapenems are recommended for treatment of Enterobacter infections with AmpC phenotypes. Although isolates are typically susceptible to cefepime in vitro, there are few data supporting its clinical efficacy. Methods. We reviewed all cases of Enterobacter species bacteremia at 2 academic hospitals from 2005 to 2011. Outcomes of interest were (1) persistent bacteremia >= 1 calendar day and (2) in-hospital mortality. We fit logistic regression models, adjusting for clinical risk factors and Pitt bacteremia score and performed propensity score analyses to compare the efficacy of cefepime and carbapenems. Results. Three hundred sixty-eight patients experienced Enterobacter species bacteremia and received at least 1 antimicrobial agent, of whom 52 (14%) died during hospitalization. Median age was 59 years; 19% were neutropenic, and 22% were in an intensive care unit on the day of bacteremia. Twenty-nine (11%) patients had persistent bacteremia for >= 1 day after antibacterial initiation. None of the 36 patients who received single-agent cefepime (0%) had persistent bacteremia, as opposed to 4 of 16 (25%) of those who received single-agent carbapenem (P <.01). In multivariable models, there was no association between carbapenem use and persistent bacteremia (adjusted odds ratio [aOR], 1.52; 95% CI,.58-3.98; P =.39), and a nonsignificant lower odds ratio with cefepime use (aOR, 0.52; 95% CI,.19-1.40; P =.19). In-hospital mortality was similar for use of cefepime and carbapenems in adjusted regression models and propensity-score matched analyses. Conclusions. Cefepime has a similar efficacy as carbapenems for the treatment of Enterobacter species bacteremia. Its use should be further explored as a carbapenem-sparing agent in this clinical scenario. C1 [Siedner, Mark J.; Ferraro, Mary Jane; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ferraro, Mary Jane] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Siedner, Mark J.; Galar, Alicia; Guzman-Suarez, Belisa B.; Kubiak, David W.; O'Brien, Thomas F.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Kubiak, David W.; Baghdady, Nour] Brigham & Womens Hosp, Dept Pharm, Boston, MA 02115 USA. RP Siedner, MJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ5, Boston, MA 02114 USA. EM msiedner@partners.org OI Galar, Alicia/0000-0002-9310-8752 FU National Institute of Mental Health [NIH K23 MH099916]; National Institute of General Medical Sciences [NIH R01 GM103525] FX M. J. S. receives support from the National Institute of Mental Health (NIH K23 MH099916) and T. F. O. receives support from the National Institute of General Medical Sciences (NIH R01 GM103525). NR 35 TC 18 Z9 18 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2014 VL 58 IS 11 BP 1554 EP 1563 DI 10.1093/cid/ciu182 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AI7AL UT WOS:000337031200011 PM 24647022 ER PT J AU Bogoch, II Scully, EP Zachary, KC Yawetz, S Mayer, KH Bell, CM Andrews, JR AF Bogoch, Isaac I. Scully, Eileen P. Zachary, Kimon C. Yawetz, Sigal Mayer, Kenneth H. Bell, Chaim M. Andrews, Jason R. TI Patient Attrition Between the Emergency Department and Clinic Among Individuals Presenting for HIV Nonoccupational Postexposure Prophylaxis SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE HIV; postexposure prophylaxis; prevention; care linkage; retention ID SEXUAL ASSAULT; PREEXPOSURE PROPHYLAXIS; TENOFOVIR DF; ADHERENCE; EXPOSURE; MEN; SEROCONVERSION; EMTRICITABINE; TOLERABILITY; METAANALYSIS AB Background. Nonoccupational postexposure prophylaxis (nPEP) is recommended after a sexual or parenteral exposure to human immunodeficiency virus (HIV). Patients frequently seek care in an emergency department (ED) after an exposure and are usually referred to an HIV clinic for further management. There have been few data on determinants of attrition after presentation to EDs for nPEP. Methods. From July 2010 to June 2011, we prospectively recorded all referrals to nPEP programs from 2 large EDs at 2 academic medical centers in Boston, Massachusetts. Data were recorded on patient demographics, nature of potential HIV exposures, referrals to and attendance at HIV clinics, and reported completion of 28 days of antiretroviral therapy (ART). Multivariable logistic regression was used to evaluate risk factors for (1) patient attrition between the ED and HIV clinic follow-up and (2) documented completion of ART. Results. Of 180 individuals who were referred to clinic follow-up for nPEP care from the ED, 98 (54.4%) attended a first nPEP clinic visit and 43 (23.9%) had documented completion of a 28-day course of ART. Multivariable analysis revealed older age (adjusted odds ratio [aOR], 0.96; 95% confidence interval [CI],.93-.99) and self-payment (aOR, 0.32; 95% CI,.11-.97) were significant predictors for failing to attend an initial HIV clinic appointment. Women were less likely than men to complete a 28-day ART regimen (aOR, 0.34; 95% CI,.15-.79). Conclusions. Commonly used nPEP delivery models may not be effective for all patients who present with nonoccupational exposures to HIV. Interventions are needed to improve rates of follow-up and completion of nPEP to reduce the risk of preventable HIV infections. C1 [Bogoch, Isaac I.] Univ Hlth Network, Div Internal Med, London, ON, Canada. [Bogoch, Isaac I.] Univ Hlth Network, Div Infect Dis, London, ON, Canada. [Bell, Chaim M.] Mt Sinai Hosp, Div Internal Med, Toronto, ON, Canada. [Bogoch, Isaac I.; Bell, Chaim M.] Univ Toronto, Fac Med, Toronto, ON M5S 1A1, Canada. [Scully, Eileen P.; Yawetz, Sigal] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Scully, Eileen P.; Zachary, Kimon C.; Yawetz, Sigal; Mayer, Kenneth H.; Andrews, Jason R.] Harvard Univ, Sch Med, Boston, MA USA. [Zachary, Kimon C.; Andrews, Jason R.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Mayer, Kenneth H.] Fenway Hlth, Boston, MA USA. RP Bogoch, II (reprint author), Toronto Gen Hosp, 14EN 209,200 Elizabeth S, Toronto, ON M5G 2C4, Canada. EM isaac.bogoch@uhn.ca RI Bell, Chaim/C-4611-2015 OI Bell, Chaim/0000-0002-3778-9469 FU Canadian Institute of Health Research (CIHR); Canadian Patient Safety Institute Chair in Patient Safety and Continuity of Care; Merck; Gilead; Bristol-Meyers-Squibb FX I. I. B. is supported by a Canadian Institute of Health Research (CIHR) fellowship award; C. M. B. is supported by a CIHR and Canadian Patient Safety Institute Chair in Patient Safety and Continuity of Care; and K. H. M. has unrestricted research grants from Merck, Gilead and Bristol-Meyers-Squibb. NR 23 TC 12 Z9 13 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2014 VL 58 IS 11 BP 1618 EP 1624 DI 10.1093/cid/ciu118 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA AI7AL UT WOS:000337031200020 PM 24723288 ER PT J AU Weir, CR Butler, J Thraen, I Woods, PA Hermos, J Ferguson, R Gleason, T Barrus, R Fiore, L AF Weir, Charlene R. Butler, Jorie Thraen, Iona Woods, Patricia A. Hermos, John Ferguson, Ryan Gleason, Theresa Barrus, Robyn Fiore, Louis TI Veterans Healthcare Administration providers' attitudes and perceptions regarding pragmatic trials embedded at the point of care SO CLINICAL TRIALS LA English DT Article ID CLINICAL-RESEARCH; EQUIPOISE; RECRUITMENT; UNCERTAINTY; BARRIERS; ETHICS; TIME AB Background The Veterans Healthcare Administration (VA) is implementing an adaptation of a pragmatic trial program, Point of Care Research (POC-R). The goal of POC-R is to embed research into clinical practice, contributing to a Learning Healthcare System. Provider acceptance and participation in POC-R is essential to its successful implementation. The purpose of this study is to evaluate provider's perceptions and beliefs regarding the POC-R program. Methods Provider focus groups and interviews were conducted at seven VA medical facilities involving 62 providers. A semi-structured script was used that included descriptions of four use cases and targeted questions regarding perceptions, concerns, and attitudes about the POC-R program. Sessions were audio-taped, de-identified, transcribed, and analyzed using systematic qualitative techniques to create response categories and overarching themes. Results The emergent themes were as follows: (1) POC-R is a valuable component of evidence-based practice, providing an opportunity to base clinical practice on more generalizable evidence as well as providing tools to improve local practice; (2) POC-R highlights the tension between the need for autonomy of practice and compliance with protocols; (3) POC-R may create increased time and burden resulting from added research responsibilities; (4) concern about the scientific validity and reliability of results; (5) potential for a negative impact on the provider-patient relationship; and (6) uncertainty regarding what constitutes equipoise, given differences in provider knowledge and preferences. Despite substantive concerns, barriers were generally felt to be solvable. Implementation should include provider education, careful attention to workflow for all arms of the study, inclusion of the entire team, and adequate oversight. Limitations The study design is qualitative with limited implications for causal inference. Participants are from the VA and may not be representative of other clinicians. Conclusion VA providers are supportive of the importance and value of pragmatic trials in general and of POC-R in particular. However, providers have significant concerns regarding the burden, ethics, and evidence regarding equipoise. Results are discussed in terms of implementation recommendations. C1 [Weir, Charlene R.; Butler, Jorie; Thraen, Iona; Barrus, Robyn] VA Ctr Informat Decis Enhancement & Surveillance, Salt Lake City, UT 84105 USA. [Weir, Charlene R.; Butler, Jorie; Thraen, Iona; Barrus, Robyn] VA Salt Lake City SLC Hlth Care Syst, GRECC, Salt Lake City, UT 84105 USA. [Weir, Charlene R.] Univ Utah, Sch Med, Dept Biomed Informat, Salt Lake City, UT USA. [Woods, Patricia A.; Hermos, John; Ferguson, Ryan; Fiore, Louis] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr MA, VA Cooperat Studies Program, US Dept Vet Affairs, Boston, MA USA. [Hermos, John; Fiore, Louis] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Ferguson, Ryan; Fiore, Louis] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Gleason, Theresa] US Dept Vet Affairs, Dept Vet Affairs, Off Res & Dev, Washington, DC USA. RP Weir, CR (reprint author), VA Ctr Informat Decis Enhancement & Surveillance, 500 Foothill Blvd 182, Salt Lake City, UT 84105 USA. EM Charlene.weir@utah.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Clinical Science Research & Development Service [VA ID: SPLF-001-11S] FX This study was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Clinical Science Research & Development Service (VA ID: SPLF-001-11S). Dr Weir is the Associate Director of the Informatics Decision Enhancement and Surveillance (IDEAS) Center of Innovation at the VA Salt Lake City, Utah. NR 24 TC 1 Z9 1 U1 0 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PD JUN PY 2014 VL 11 IS 3 BP 292 EP 299 DI 10.1177/1740774514523848 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI3UX UT WOS:000336791500003 PM 24651565 ER PT J AU Saini, J Bansal, V Chandra, A Madan, J Jain, UK Chandra, R Jain, SM AF Saini, Jyoti Bansal, Vikas Chandra, Ankush Madan, Jitender Jain, Upendra Kumar Chandra, Ramesh Jain, Sarvesh Malviya TI Bleomycin sulphate loaded nanostructured lipid particles augment oral bioavailability, cytotoxicity and apoptosis in cervical cancer cells SO COLLOIDS AND SURFACES B-BIOINTERFACES LA English DT Article DE Bleomycin sulphate; Nanostructured lipid particles; Cytotoxicity; Apoptosis; Cellular uptake; Bioavailability ID INTRACELLULAR DELIVERY; SURFACE-CHEMISTRY; CELLULAR UPTAKE; NANOPARTICLES; PHARMACOKINETICS; SYSTEMS; MICROENVIRONMENT; CHEMOTHERAPY; PERSPECTIVE; LIPOSOMES AB In present investigation, bleomycin sulphate loaded nanostructured lipid particles (BLM-NLPs) were constructed to enhance the oral bioavailability by overwhelming the first pass hepatic metabolism. The particles size and nanoencapsulation efficiency of BLM-NLPs were measured to be 17.4 +/- 5.4 nm and 45.3 +/- 3.4%, respectively. Our studies indicated that the drug was molecularly dispersed in the lipid nanocoacervates, with amorphous geometry, without altering the chemical structure, as ascertained by spectral studies. The nanoformulation, BLM-NLPs was analyzed for dissolution testing, cytotoxicity, apoptosis and cellular uptake in human cervical cancer cell line, HeLa cells. BLM-NLPs released the drug with first order kinetic in simulated intestinal fluid (pH similar to 6.8 +/- 0.1), characterized by initial burst and followed by slow release. Further, an enhanced cytotoxicity (similar to 5.6 fold lower IC50), improved intracellular concentration (similar to 4.38 fold) and greater degree of apoptosis was induced by BLM-NLPs in HeLa cells, as compared to BLM alone. Moreover, BLM-NLPs also showed dose-dependent internalization, as evinced by cellular uptake study. The in vivo study indicated a significantly (P < 0.0001) smaller elimination rate constant (K-E), volume of distribution (V-d) and clearance rate (CLTotal) for BLM-NLPs, as compared to BLM solution in post-oral administrations. This clearly depicts the retention and stability of tailored nanoformulation in intestinal absorption pathway. In addition, our nanoformulation, BLM-NLPs documented significantly (P < 0.0001) similar to 3.4 fold (66.20 +/- 2.57%) higher bioavailability than BLM solution (19.56 +/- 0.79%). In conclusion, our in vitro and in vivo results warrant the safety, efficacy and potency of tailored nanoformulation in clinical settings. (C) 2014 Elsevier B.V. All rights reserved. C1 [Saini, Jyoti; Bansal, Vikas; Madan, Jitender; Jain, Upendra Kumar] Chandigarh Coll Pharm, Dept Pharmaceut, Mohali 140307, Punjab, India. [Chandra, Ankush] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chandra, Ramesh] Univ Delhi, Dr BR Ambedkar Ctr Biomed Res, Delhi 110007, India. [Jain, Sarvesh Malviya] Oniosome Hlth Care Private Ltd, Mohali 160071, Punjab, India. RP Madan, J (reprint author), Chandigarh Coll Pharm, Dept Pharmaceut, Mohali 140307, Punjab, India. EM jitenderpharmacy@gmail.com OI Chandra, Ankush/0000-0003-1843-3894 NR 50 TC 7 Z9 7 U1 2 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0927-7765 EI 1873-4367 J9 COLLOID SURFACE B JI Colloid Surf. B-Biointerfaces PD JUN 1 PY 2014 VL 118 BP 101 EP 110 DI 10.1016/j.colsurfb.2014.03.036 PG 10 WC Biophysics; Chemistry, Physical; Materials Science, Biomaterials SC Biophysics; Chemistry; Materials Science GA AI6VA UT WOS:000337013900014 PM 24732397 ER PT J AU Fathi, AT Chen, YB AF Fathi, Amir T. Chen, Yi-Bin TI Treatment of Relapse of Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation SO CURRENT HEMATOLOGIC MALIGNANCY REPORTS LA English DT Article DE Acute myeloid leukemia; Allogeneic hematopoietic stem cell transplantation; Relapse; Graft-vs.-host disease (GVHD); Emerging therapies ID BONE-MARROW-TRANSPLANTATION; DONOR LYMPHOCYTE INFUSIONS; ACUTE MYELOGENOUS LEUKEMIA; DOSE CYTOSINE-ARABINOSIDE; INTERNAL TANDEM DUPLICATION; UMBILICAL-CORD BLOOD; G-CSF CLAG; OLDER PATIENTS; MYELODYSPLASTIC SYNDROMES; HEMATOLOGIC MALIGNANCIES AB Disease relapse remains a major cause of mortality for patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Historically, patients who experience disease relapse after HSCT have a dismal prognosis with very few long-term survivors. There is no standard treatment for patients in this situation given the variability in patient characteristics, disease biology, complications such as graft-vs.-host disease (GVHD) and infections, donor availability, and patient choice. Here, we discuss the current options for treatment of relapsed AML after HSCT including conventional chemotherapy, novel agents, donor leukocyte infusion, second allogeneic HSCT, and emerging therapies. C1 [Fathi, Amir T.] Massachusetts Gen Hosp, Ctr Leukemia, Boston, MA 02114 USA. [Chen, Yi-Bin] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. RP Chen, YB (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Cox 108,55 Fruit St, Boston, MA 02114 USA. EM afathi@partners.org; ychen6@partners.org FU Otsuka; Seattle Genetics; Bayer/Onyx; Novartis, Inc. FX Dr. Yi-Bin Chen served as a consultant for Otsuka Pharmaceuticals and Seattle Genetics. Dr. Chen received grants from Otsuka, Seattle Genetics, Bayer/Onyx, and Novartis, Inc. NR 71 TC 3 Z9 4 U1 2 U2 3 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1558-8211 EI 1558-822X J9 CURR HEMATOL MALIG R JI Curr. Hematol. Malig. Rep. PD JUN PY 2014 VL 9 IS 2 BP 186 EP 192 DI 10.1007/s11899-014-0209-2 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA AI6IE UT WOS:000336975400013 PM 24643311 ER PT J AU Hamdy, O Marchetti, A Hegazi, RA Mechanick, JI AF Hamdy, Osama Marchetti, Albert Hegazi, Refaat A. Mechanick, Jeffrey I. TI The Transcultural Diabetes Nutrition Algorithm Toolkit: Survey and Content Validation in the United States, Mexico, and Taiwan SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID CLINICAL ALGORITHM; GUIDELINES; MANAGEMENT; ADULTS AB Background: Evidence demonstrates that medical nutrition therapy (MNT) in prediabetes and type 2 diabetes (T2D) improves glycemic control and reduces diabetes risks and complications. Consequently, MNT is included in current clinical practice guidelines. Guideline recommendations, however, are frequently limited by their complexity, contradictions, personal and cultural rigidity, and compromised portability. The transcultural Diabetes Nutrition Algorithm (tDNA) was developed to overcome these limitations. To facilitate tDNA uptake and usage, an instructional Patient Algorithm Therapy (PATh) toolkit was created. Content validation of tDNA-PATh is needed before widespread implementation. Subjects and Methods: Healthcare providers (n = 837) in Mexico (n = 261), Taiwan (n = 250), and the United States (n = 326) were questioned about challenges implementing MNT in clinical practice and the projected utilization and impact of tDNA-PATh. To assess the international portability and applicability of tDNA-PATh, the survey was conducted in countries with distinct ethnic and cultural attributes. Potential respondents were screened for professional and practice demographics related to diabetes. The questionnaire was administered electronically after respondents were exposed to core tDNA-PATh components. Results: Overall, 61% of respondents thought that tDNA-PATh could help overcome MNT implementation challenges, 91% indicated positive impressions, 83% believed they would adopt tDNA-PATh, and 80% thought tDNA-PATh would be fairly easy to implement. Conclusions: tDNA-PATh appears to be an effective culturally sensitive tool to foster MNT in clinical practice. By providing simple culturally specific instructions, tDNA-PATh may help to overcome current impediments to implementing recommended lifestyle modifications. Specific guidance provided by tDNA-PATh, together with included patient education materials, may increase healthcare provider efficiency. C1 [Hamdy, Osama] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [Marchetti, Albert] Med Educ & Res Alliance Inc, New York, NY USA. [Marchetti, Albert] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Hegazi, Refaat A.] Abbott Nutr, Columbus, OH USA. [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY USA. RP Marchetti, A (reprint author), Med Educ & Res Alliance Inc, 12 Haines Ave, Linwood, NJ 08221 USA. EM albertmarchetti@yahoo.com FU Abbott Nutrition International FX The development of this article was funded by Abbott Nutrition International. NR 15 TC 6 Z9 6 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 EI 1557-8593 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD JUN PY 2014 VL 16 IS 6 BP 378 EP 384 DI 10.1089/dia.2013.0276 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI5GS UT WOS:000336894200007 PM 24471559 ER PT J AU Edrey, YH Salmon, AB AF Edrey, Yael H. Salmon, Adam B. TI Revisiting an age-old question regarding oxidative stress SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE Aging; Life span; Longevity; Age-related disease; Mouse models; Free radicals ID METHIONINE-SULFOXIDE-REDUCTASE; MANGANESE SUPEROXIDE-DISMUTASE; REPLICATIVE LIFE-SPAN; TRANSGENIC MICE; MUSCLE ATROPHY; INSULIN-RESISTANCE; MITOCHONDRIAL-FUNCTION; ALZHEIMERS-DISEASE; KNOCKOUT MOUSE; IN-VIVO AB Significant advances in maintaining health;throughout life can be made through a clear understanding of the fundamental mechanisms that regulate aging. The Oxidative Stress Theory of Aging (OSTA) is probably the most well studied mechanistic theory of aging and suggests that the rate of aging is controlled by accumulation of oxidative damage. To directly test the OSTA, aging has been measured in several lines of mice with genetic alterations in the expression of enzymatic antioxidants. Under its strictest interpretation, these studies do not support the OSTA, as modulation of antioxidant expression does not generally affect mouse life span. However, the incidence of many age-related diseases and pathologies is altered in these models, suggesting that oxidative stress does significantly influence some aspects of the aging process. Further, oxidative stress may affect aging in disparate patterns among tissues or under various environmental conditions. In this review, we summarize the current literature regarding aging in antioxidant mutant mice and offer several interpretations of their support of the OSTA. Published by Elsevier Inc. C1 [Edrey, Yael H.; Salmon, Adam B.] Sam & Ann Barshop Inst Longev & Aging Studies & S, San Antonio, TX 78229 USA. [Salmon, Adam B.] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78229 USA. [Salmon, Adam B.] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA. RP Salmon, AB (reprint author), South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM salmona@uthscsa.edu FU Geriatric Research, Education and Clinical Center of the South Texas Veterans Health Care Systems; San Antonio Nathan Shock Center [NIA 5P30 AG013319-19]; San Antonio Area Foundation FX The authors thank Arlan Richardson, Holly Van Remmen, and Yuji Ikeno for discussions that led to the compilation of this review and their yeoman's work over the past 15+ years in regard to testing the OSTA under the criteria above. This work was supported by the Geriatric Research, Education and Clinical Center of the South Texas Veterans Health Care Systems, a pilot grant from the San Antonio Nathan Shock Center (NIA 5P30 AG013319-19), and a Biomedical Research Grant from the San Antonio Area Foundation. NR 128 TC 24 Z9 24 U1 1 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUN PY 2014 VL 71 BP 368 EP 378 DI 10.1016/j.freeradbiomed.2014.03.038 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AI5FP UT WOS:000336891100033 PM 24704971 ER PT J AU Morris, DL Fernando, MMA Taylor, KE Chung, SA Nititham, J Alarcon-Riquelme, ME Barcelloss, LF Behrens, TW Cotsapas, C Gaffney, PM Graham, RR Pons-Estel, BA Gregersen, PK Harley, JB Hauser, SL Hom, G Langefeld, CD Noble, JA Rioux, JD Seldin, MF Vyse, TJ Criswell, LA AF Morris, D. L. Fernando, M. M. A. Taylor, K. E. Chung, S. A. Nititham, J. Alarcon-Riquelme, M. E. Barcelloss, L. F. Behrens, T. W. Cotsapas, C. Gaffney, P. M. Graham, R. R. Pons-Estel, B. A. Gregersen, P. K. Harley, J. B. Hauser, S. L. Hom, G. Langefeld, C. D. Noble, J. A. Rioux, J. D. Seldin, M. F. Vyse, T. J. Criswell, L. A. CA Syst Lupus Erythematosus Genet Con TI MHC associations with clinical and autoantibody manifestations in European SLE SO GENES AND IMMUNITY LA English DT Article DE Sub-phenotype analysis; MHC; meta-analysis; genetics; systemic lupus erythematosus; Europeans ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; RO SS-A; SUSCEPTIBILITY VARIANTS; RHEUMATOID-ARTHRITIS; LOCI; MODEL; DISEASES; REGION AB Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis- of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies. C1 [Morris, D. L.; Fernando, M. M. A.; Vyse, T. J.] Guys Hosp, Kings Coll London, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England. [Taylor, K. E.; Chung, S. A.; Nititham, J.] Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthrit, San Francisco, CA USA. [Alarcon-Riquelme, M. E.] Pfizer Univ Granada Junta de Andalucia, Ctr Genom & Invest Oncol, GENYO, Dept Human DNA Variabil, Granada, Spain. [Alarcon-Riquelme, M. E.; Gaffney, P. M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Barcelloss, L. F.] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Genet Epidemiol & Genom Lab, Berkeley, CA 94720 USA. [Behrens, T. W.; Graham, R. R.; Hom, G.] Genentech Inc, Immunol Biomarkers Grp, San Francisco, CA USA. [Cotsapas, C.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. [Pons-Estel, B. A.] Hosp Prov Rosario, Rheumatol Serv, Rosario, Argentina. [Gregersen, P. K.] North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY USA. [Harley, J. B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Harley, J. B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Hauser, S. L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Langefeld, C. D.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Wake Forest, NC USA. [Noble, J. A.] Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. [Rioux, J. D.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Rioux, J. D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Seldin, M. F.] Univ Calif Davis, Davis, CA 95616 USA. RP Morris, DL (reprint author), Guys Hosp, Kings Coll London, Sch Med, Dept Med & Mol Genet, London SE1 9RT, England. EM david.l.morris@kcl.ac.uk RI Rioux, John/A-9599-2015; OI Rioux, John/0000-0001-7560-8326; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154; Cotsapas, Chris/0000-0002-7772-5910 FU Swedish Research Council, lnstituto de Salud Carlos III [PI12/02558]; FEDER; EU; BIOLUPUS RNP; European Science Foundation; American College of Rheumatology Rheumatology Research Foundation Physician Scientist Development Award; National Institutes of Health; National Center for Advancing Translational Sciences through UCSF-CTSI [KL2TR000143]; Clinician Scientist Fellowship [18239]; DLM [17761/PI TJV]; Swedish Research Council and Instituto de Salud Carlos III [PS09/00129]; FEDER funds of the European Union; Consejeria de Salud de Andalucia [PI0012]; National Institutes of Allergy and Infectious Diseases [AI067152]; Wellcome Trust Case-Control Consortium [076113, 085475]; NIH [AR052300, AR02175, AR22804, AR42460, AI024717, AI083194, AR62277, AI082714, AI53747, AI31584, DE15223, RR20143, PR094002, AI62629, AR48940, AR19084, AR043274, AI063274, AI40076, AR052125, HG006828, AR048929, AR049084] FX We thank the original study participants and their families for their contributions to this research, along with clinical colleagues who facilitated data collection. We thank Alexander Dilthey for his advice during the HLA imputation. We also thank the investigators of IMAGEN (John D Rioux, Philippe Goyette, Timothy J Vyse, Lennart Hammarstrom, Michelle MA Fernando, Todd Green, Philip L De Jager, Sylvain Foisy, Joanne Wang, Paul IW de Bakker, Stephen Leslie, Gilean McVean, Leonid Padyukov, Lars Alfredsson, Vito Annese, David A Hafler, Qiang Pan-Hammarstrom, Ritva Matell, Stephen J Sawcer, Alastair D Compston, Bruce AC Cree, Daniel B Mirel, Mark J Daly, Tim W Behrens, Lars Klareskog, Peter K Gregersen, Jorge R Oksenberg and Stephen L Hauser).; A full list of the investigators who contributed to the generation of the Wellcome Trust Case-Control Consortium data is available from the WTCCC website (see Web Resources).; This study was founded by Swedish Research Council, lnstituto de Salud Carlos III (PI12/02558) partly financed by FEDER funds of the EU, and the BIOLUPUS RNP funded by the European Science Foundation to MEA-R; American College of Rheumatology Rheumatology Research Foundation Physician Scientist Development Award and National Institutes of Health, National Center for Advancing Translational Sciences through UCSF-CTSI Grant KL2TR000143 to SAC.; Arthritis Research UK funded a Clinician Scientist Fellowship for MMAF (ref 18239) and the Arthritis Research UK funded DLM under (ref 17761/PI TJV). MEA-R was funded by the Swedish Research Council and Instituto de Salud Carlos III grant number PS09/00129 cofinanced through FEDER funds of the European Union and the Consejeria de Salud de Andalucia PI0012.; The IMAGEN consortium was supported by Grant AI067152 from the National Institutes of Allergy and Infectious Diseases.; Funding for the Wellcome Trust Case-Control Consortium project was provided by the Wellcome Trust under award 076113 and 085475.; Cord blood samples were collected by V L Nimgaonkar's group at the University of Pittsburgh, as part of a multi-institutional collaborative research project with J Smoller, MD DSc and P Sklar, MD PhD. (Massachusetts General Hospital; grant MH 63420).; Support for the Illumina MHC Panel study was provided by the NIH (AR052300, AR02175, AR22804, AR62277, AR42460, AI024717, AI083194, AR62277, AI082714, AI53747, AI31584, DE15223, RR20143, PR094002, AI62629, AR48940, AR19084, AR043274, AI063274, AI40076, AR052125, HG006828, AR048929, and AR049084), research grants from the US Department of Veterans Affairs, US Department of Defense (PR094002), American College of Rheumatology, Alliance for Lupus Research, Rheuminations, the Lupus Foundation of Minnesota and the Mary Kirkland Center for Lupus Research. This study was performed in part in the General Clinical Research Center, Moffitt Hospital, University of California San Francisco, with funds provided by the National Center for Research Resources, 5 M01 RR-00079, US Public Health Service. NR 26 TC 17 Z9 18 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 EI 1476-5470 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2014 VL 15 IS 4 BP 210 EP 217 DI 10.1038/gene.2014.6 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA AI5CT UT WOS:000336883700002 PM 24598797 ER PT J AU Wojcik, GL Thio, CL Kao, WHL Latanich, R Goedert, JJ Mehta, SH Kirk, GD Peter, MG Cox, AL Kims, AY Chungs, RT Thomas, DL Duggal, P AF Wojcik, G. L. Thio, C. L. Kao, W. H. L. Latanich, R. Goedert, J. J. Mehta, S. H. Kirk, G. D. Peter, M. G. Cox, A. L. Kims, A. Y. Chungs, R. T. Thomas, D. L. Duggal, P. TI Admixture analysis of spontaneous hepatitis C virus clearance in individuals of African descent SO GENES AND IMMUNITY LA English DT Article ID GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; INFECTION; IL28B; INFERENCE; ANCESTRY; HOST; MAP AB Hepatitis C virus (HCV) infects an estimated 3% of the global population with the majority of individuals (75-85%) failing to clear the virus without treatment, leading to chronic liver disease. Individuals of African descent have lower rates of clearance compared with individuals of European descent and this is not fully explained by social and environmental factors. This suggests that differences in genetic background may contribute to this difference in clinical outcome following HCV infection. Using 473 individuals and 792 721 single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS), we estimated local African ancestry across the genome. Using admixture mapping and logistic regression, we identified two regions of interest associated with spontaneous clearance of HCV (15q24, 20p12). A genome-wide significant variant was identified on chromosome 15 at the imputed SNP, rs55817928 (P=6.18 x 10(-8)) between the genes SCAPER and RCN. Each additional copy of the African ancestral C allele is associated with 2.4 times the odds of spontaneous clearance. Conditional analysis using this SNP in the logistic regression model explained one-third of the local ancestry association. Additionally, signals of selection in this area suggest positive selection due to some ancestral pathogen or environmental pressure in African, but not in European populations. C1 [Wojcik, G. L.; Kao, W. H. L.; Mehta, S. H.; Kirk, G. D.; Thomas, D. L.; Duggal, P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Thio, C. L.; Kao, W. H. L.; Latanich, R.; Cox, A. L.; Thomas, D. L.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Goedert, J. J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Peter, M. G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Kims, A. Y.; Chungs, R. T.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Duggal, P (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E6539, Baltimore, MD 21205 USA. EM pduggal@jhsph.edu FU Office of AIDS Research through the Center for Inherited Diseases at Johns Hopkins University; National Institute on Drug Abuse [R01DA013324, DA033541, DA012568, DA04334]; National Institute of Allergy and Infectious Diseases [U19AI088791, AI082630, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Frederick National Laboratory for Cancer Research [HHSN261200800001E]; Intramural Research Programs of the National Institutes of Health; Frederick National Laboratory for Cancer Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness Other Communication Disorders; National Center for Research Resources (UCSF-CTSI Grant) [UL1 RR024131]; Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research FX Primary data are available through the central NIH GWAS data repository at the National Center for Biotechnology Information (NCBI), National Library of Medicine (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html). This project was funded in whole or in part by the Office of AIDS Research through the Center for Inherited Diseases at Johns Hopkins University, the National Institute on Drug Abuse (R01DA013324, DA033541, DA012568 and DA04334), the National Institute of Allergy and Infectious Diseases (U19AI088791 and AI082630), and the Frederick National Laboratory for Cancer Research (contract HHSN261200800001E). This research was supported in part by the Intramural Research Programs of the National Institutes of Health and the Frederick National Laboratory for Cancer Research. The WINS is funded by the National Institute of Allergy and Infectious Diseases (U01-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993 and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research. NR 29 TC 0 Z9 0 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 EI 1476-5470 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2014 VL 15 IS 4 BP 241 EP 246 DI 10.1038/gene.2014.11 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA AI5CT UT WOS:000336883700006 PM 24622687 ER PT J AU Stewart, DR Brems, H Gomes, AG Ruppert, SL Callens, T Williams, J Claes, K Bober, MB Hachen, R Kaban, LB Li, H Lin, A McDonald, M Melancon, S Ortenberg, J Radtke, HB Samson, I Saul, RA Shen, J Siqveland, E Toler, TL van Maarle, M Wallace, M Williams, M Legius, E Messiaen, L AF Stewart, Douglas R. Brems, Hilde Gomes, Alicia G. Ruppert, Sarah L. Callens, Tom Williams, Jennifer Claes, Kathleen Bober, Michael B. Hachen, Rachel Kaban, Leonard B. Li, Hua Lin, Angela McDonald, Marie Melancon, Serge Ortenberg, June Radtke, Heather B. Samson, Ignace Saul, Robert A. Shen, Joseph Siqveland, Elizabeth Toler, Tomi L. van Maarle, Merel Wallace, Margaret Williams, Misti Legius, Eric Messiaen, Ludwine TI Jaffe-Campanacci syndrome, revisited: detailed clinical and molecular analyses determine whether patients have neurofibromatosis type 1, coincidental manifestations, or a distinct disorder SO GENETICS IN MEDICINE LA English DT Article DE cafe-au-lait macule; giant cell lesion; Jaffe-Campanacci syndrome; neurofibromatosis type 1; nonossifying-fibroma ID GIANT-CELL GRANULOMA; OF-THE-LITERATURE; NF1 GENE; ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS; MUTATIONAL SPECTRUM; PHENOTYPE; CHERUBISM; DELETIONS; TUMORS; IDENTIFICATION AB Purpose: "Jaffe-Campanacci syndrome" describes the complex of multiple nonossifying fibromas of the long bones, mandibular giant cell lesions, and cafe-au-lait macules in individuals without neurofibromas. We sought to determine whether Jaffe-Campanacci syndrome is a distinct genetic entity or a variant of neurofibromatosis type 1. Methods: We performed germline NF1, SPRED1, and GNAS1 (exon 8) mutation testing on patients with Jaffe-Cainpanacci syndrome of Jaffe-Campanacci syndrome-related features, We also performed somatic NF1 mutation testing on nonossifying fibromas and giant, cell lesions. Results: Pathogenic germline NF1 mutations Were identified 13 of 14 patients with multiple cafe-au-lait macules and niultiple non-ossifying fibromas or giant cell lesions ("classicar Jaffe-Campanacci syndrome); all 13 also fulfilled the National Institues of Health diagnostic criteria for neurofibromatosis type 1. Somatic NFI mutations were detected in two giant cell lesions but not in two nonossifying fibromas. No SPRED1 or GNAS1 (exon 8) mutations were detected in the seven NF1-negative patients with Jaffe-Campanacci syndrome, nonossifying fibromas, or giant cell lesions. Conclusion: In this study, the majority of patients with cafe-au-lait macules and nonossifying fibromas Or giant cell lesions harbored a pathogenic gerinline NF1 mutation,suggesting that many Jaffe-Campanacci syndrome cases may-actually have neurofibromatosis type 1. We provide the first proof of specific somatic second-hit mutations affecting NFI in two giant cell lesions from two unrelated patients, establishing these as neurofibromatosis type 1-associated tumors. C1 [Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol, NIH, Rockville, MD 20850 USA. [Brems, Hilde; Legius, Eric] Univ Louvain, Dept Human Genet, Louvain, Belgium. [Brems, Hilde; Legius, Eric] Leuven Univ Hosp, Ctr Human Genet, Louvain, Belgium. [Gomes, Alicia G.; Callens, Tom; Williams, Jennifer; Messiaen, Ludwine] Univ Alabama Birmingham, Dept Genet, Med Genom Lab, Birmingham, AL USA. [Ruppert, Sarah L.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium. [Bober, Michael B.] Alfred I DuPont Hosp Children, Dept Pediat, Div Med Genet, Wilmington, DE USA. [Hachen, Rachel] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Li, Hua; Wallace, Margaret] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA. [Lin, Angela] MassGen Hosp Children, Genet Unit, Boston, MA USA. [McDonald, Marie] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [McDonald, Marie] Duke Univ, Med Ctr, Dept Med Genet, Durham, NC USA. [Melancon, Serge; Ortenberg, June] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Med Genet, Montreal, PQ H3H 1P3, Canada. [Melancon, Serge; Ortenberg, June] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Pediat, Montreal, PQ H3H 1P3, Canada. [Radtke, Heather B.] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Samson, Ignace] Univ Hosp Leuven, Dept Orthoped Surg, Louvain, Belgium. [Saul, Robert A.] Greenwood Genet Ctr, Greenwood, SC 29646 USA. [Shen, Joseph] Childrens Hosp Cent Calif, Madera, CA USA. [Siqveland, Elizabeth] Childrens Hosp & Clin Minnesota, Dept Genet, Minneapolis, MN USA. [Toler, Tomi L.] Massachusetts Gen Hosp, Div Med Genet, Boston, MA 02114 USA. [van Maarle, Merel] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Williams, Misti] LewisGale Reg Hlth Syst, Dept Clin Genet, Salem, VA USA. RP Stewart, DR (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol, NIH, Rockville, MD 20850 USA. EM drstewart@mail.nih.gov; lmessiaen@uabmc.edu OI Bober, Michael/0000-0002-6178-1264; Toler, Tomi/0000-0002-1637-8310 FU Medical Genomics Laboratory at the University of Alabama Birmingham; Hayward Foundation (MRW laboratory); Division of Intramural Research of the National Human Genome Research Institute (NHGRI); Division of Cancer Epidemiology and Genetics of the National Cancer Institute's Intramural Research Program; National Cancer Institute, National Institutes of Health; Research Foundation Flanders (FWO) at the KULeuven; Clinical Research Foundation of the University Hospitals Leuven; FWO-Vlaanderen [G057806N] FX This work was supported by internal funds from the Medical Genomics Laboratory at the University of Alabama Birmingham, the Hayward Foundation (MRW laboratory), the Division of Intramural Research of the National Human Genome Research Institute (NHGRI), the Division of Cancer Epidemiology and Genetics of the National Cancer Institute's Intramural Research Program, and in part with federal funds from the National Cancer Institute, National Institutes of Health. H.B. is a postdoctoral researcher of the Research Foundation Flanders (FWO) at the KULeuven. The authors thank Kathleen Freson (Molecular and Vascular Biology, KULeuven) for GNAS1 mutation analysis. E.L. is supported by the Clinical Research Foundation of the University Hospitals Leuven and by a grant from the FWO-Vlaanderen (G057806N). NR 43 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 EI 1530-0366 J9 GENET MED JI Genet. Med. PD JUN PY 2014 VL 16 IS 6 BP 448 EP 459 DI 10.1038/gim.2013.163 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA AI6UF UT WOS:000337011800005 PM 24232412 ER PT J AU Opoliner, A Blacker, D Fitzmaurice, G Becker, A AF Opoliner, April Blacker, Deborah Fitzmaurice, Garrett Becker, Anne TI Challenges in assessing depressive symptoms in Fiji: A psychometric evaluation of the CES-D SO INTERNATIONAL JOURNAL OF SOCIAL PSYCHIATRY LA English DT Article DE CES-D; Fiji; validity; reliability; cross-cultural ID GLOBAL MENTAL-HEALTH; EPIDEMIOLOGIC-STUDIES-DEPRESSION; SCALE; DISORDERS; RELIABILITY; VALIDITY; JAPANESE; SUICIDE AB Background and Aim: The CES-D is a commonly used self-report assessment for depressive symptomatology. However, its psychometric properties have not been evaluated in Fiji. This study aims to evaluate the reliability and validity of English language and Fijian vernacular versions in ethnic Fijian adolescent schoolgirls. Methods: As part of the HEALTHY Fiji study, ethnic Fijian female adolescents (N = 523) completed the CES-D. Participants selected to respond in English or the local vernacular. Reliability (internal consistency, item-total score correlation, and test-retest estimates), validity (associations with other proxies for depression) and factor structure were assessed. Evaluations considered differences between language versions. Results: In this sample, the CES-D had a Cronbach's of 0.81 and item-total score correlation coefficients ranged between 0.2 and 0.63. One week test-retest reliability (ICC(2)) was 0.57. CES-D scores were higher among individuals who endorsed feelings of depression and suicidality compared to those who did not. ROC analyses of the CES-D versus binary depression and suicidality variables produced AUCs around 0.70 and did not support a discrete cut-off for significant disturbance. Findings were similar across the two language groups. Conclusions: The CES-D has acceptable reliability and validity among ethnic Fijian female adolescents in English and in the Fijian vernacular language. Findings support its utility as a dimensional measure for depressive symptomatology in this study population. Further examination of its clinical utility for case finding for depression in Fijian school-based and community populations is warranted. C1 [Opoliner, April; Blacker, Deborah] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02155 USA. [Blacker, Deborah; Becker, Anne] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Fitzmaurice, Garrett] Harvard Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02155 USA. [Fitzmaurice, Garrett] McLean Hosp, Belmont, MA 02178 USA. [Becker, Anne] Harvard Univ, Dept Global Hlth & Social Med, Sch Med, Boston, MA 02155 USA. RP Opoliner, A (reprint author), Harvard Univ, Dept Epidemiol, Sch Publ Hlth, 677 Huntington Ave, Boston, MA 02155 USA. EM aopoline@hsph.harvard.edu FU NIMH NIH HHS [K23MH068575, K23 MH068575] NR 36 TC 1 Z9 1 U1 1 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0020-7640 EI 1741-2854 J9 INT J SOC PSYCHIATR JI Int. J. Soc. Psychiatr. PD JUN PY 2014 VL 60 IS 4 BP 367 EP 376 DI 10.1177/0020764013490871 PG 10 WC Psychiatry SC Psychiatry GA AI3VE UT WOS:000336792300007 PM 23877336 ER PT J AU Barry, MJ AF Barry, Michael J. TI Incidentaloma Fatigue SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID NODULES C1 [Barry, Michael J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barry, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,Ninth Floor, Boston, MA 02114 USA. EM mbarry@partners.org NR 7 TC 1 Z9 1 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 JUN PY 2014 VL 174 IS 6 BP 851 EP 852 DI 10.1001/jamainternmed.2014.672 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AI4OA UT WOS:000336843500008 PM 24733384 ER PT J AU Huffman, JC Mastromauro, CA Beach, SR Celano, CM DuBois, CM Healy, BC Suarez, L Rollman, BL Januzzi, JL AF Huffman, Jeff C. Mastromauro, Carol A. Beach, Scott R. Celano, Christopher M. DuBois, Christina M. Healy, Brian C. Suarez, Laura Rollman, Bruce L. Januzzi, James L. TI Collaborative Care for Depression and Anxiety Disorders in Patients With Recent Cardiac Events The Management of Sadness and Anxiety in Cardiology (MOSAIC) Randomized Clinical Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; QUALITY-OF-LIFE; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; MAJOR DEPRESSION; PANIC DISORDER; SADHART-CHF; RISK-FACTOR; VALIDITY; METAANALYSIS AB IMPORTANCE Depression and anxiety are associated with adverse cardiovascular outcomes in patients with recent acute cardiac events. There has been minimal study of collaborative care (CC) management models for mental health disorders in high-risk cardiac inpatients, and no prior CC intervention has simultaneously managed depression and anxiety disorders. OBJECTIVE To determine the impact of a low-intensity CC intervention for depression, generalized anxiety disorder, and panic disorder among patients hospitalized for an acute cardiac illness. DESIGN, SETTING, AND PARTICIPANTS Single-blind randomized clinical trial, with study assessors blind to group assignment, from September 2010 through July 2013 of 183 patients admitted to inpatient cardiac units in an urban academic general hospital for acute coronary syndrome, arrhythmia, or heart failure and found to have clinical depression, generalized anxiety disorder, or panic disorder on structured assessment. INTERVENTIONS Participants were randomized to 24 weeks of a low-intensity telephone-based multicomponent CC intervention targeting depression and anxiety disorders (n = 92) or to enhanced usual care (serial notification of primary medical providers; n = 91). The CC intervention used a social work care manager to coordinate assessment and stepped care of psychiatric conditions and to provide support and therapeutic interventions as appropriate. MAIN OUTCOMES AND MEASURES Improvement in mental health-related quality of life (Short Form-12 Mental Component Score [SF-12MCS]) at 24 weeks, compared between groups using a random-effects model in an intent-to-treat analysis. RESULTS Patients randomized to CC had significantly greater estimated mean improvements in SF-12MCS at 24 weeks (11.21 points [from 34.21 to 45.42] in the CC group vs 5.53 points [from 36.30 to 41.83] in the control group; estimated mean difference, 5.68 points [95% CI, 2.14-9.22]; P = .002; effect size, 0.61). Patients receiving CC also had significant improvements in depressive symptoms and general functioning, and higher rates of treatment of a mental health disorder; anxiety scores, rates of disorder response, and adherence did not differ between groups. CONCLUSIONS AND RELEVANCE A novel telephone-based, low-intensity model to concurrently manage cardiac patients with depression and/or anxiety disorders was effective for improving mental health-related quality of life in a 24-week trial. C1 [Huffman, Jeff C.; Mastromauro, Carol A.; Beach, Scott R.; Celano, Christopher M.; DuBois, Christina M.; Healy, Brian C.; Suarez, Laura; Januzzi, James L.] Harvard Univ, Sch Med, Boston, MA USA. [Huffman, Jeff C.; Mastromauro, Carol A.; Beach, Scott R.; Celano, Christopher M.; DuBois, Christina M.; Suarez, Laura] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Rollman, Bruce L.] Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA USA. [Januzzi, James L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. EM jhuffman@partners.org FU American Heart Association [10GRNT3450015] FX This research was funded by American Heart Association Grant-in-Aid 10GRNT3450015 (to Dr Huffman). NR 54 TC 50 Z9 50 U1 6 U2 18 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 JUN PY 2014 VL 174 IS 6 BP 927 EP 935 DI 10.1001/jamainternmed.2014.739 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AI4OA UT WOS:000336843500026 PM 24733277 ER PT J AU Kroenke, K AF Kroenke, Kurt TI Are the Harms of False-Positive Screening Test Results Minimal or Meaningful? SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Kroenke, Kurt] US Dept Vet Affairs, Ctr Hlth Informat & Commun, Hlth Serv Res & Dev, Indianapolis, IN USA. [Kroenke, Kurt] Regenstrief Inst Inc, Indianapolis, IN 46202 USA. [Kroenke, Kurt] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. RP Kroenke, K (reprint author), Regenstrief Inst Inc, 1050 Wishard Blvd,Fifth Floor, Indianapolis, IN 46202 USA. EM kkroenke@regenstrief.org NR 8 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN PY 2014 VL 174 IS 6 BP 961 EP 963 DI 10.1001/jamainternmed.2014.160 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA AI4OA UT WOS:000336843500032 PM 24756378 ER PT J AU Li, WQ Qureshi, AA Robinson, KC Han, JL AF Li, Wen-Qing Qureshi, Abrar A. Robinson, Kathleen C. Han, Jiali TI Sildenafil Use and Increased Risk of Incident Melanoma in US Men A Prospective Cohort Study SO JAMA INTERNAL MEDICINE LA English DT Article ID ERECTILE DYSFUNCTION; CARDIAC DYSFUNCTION; MALIGNANT-MELANOMA; SKIN-CANCER; INHIBITORS; CELLS; METAANALYSIS; MUTATIONS; PATHWAY; DISEASE AB IMPORTANCE The RAS/RAF/mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) kinase/ERK cascade plays a crucial role in melanoma cell proliferation and survival. Sildenafil citrate (Viagra) is a phosphodiesterase (PDE) 5A inhibitor commonly used for erectile dysfunction. Recent studies have shown that BRAF activation down-regulates PDE5A levels, and low PDE5A expression by BRAF activation or sildenafil use increases the invasiveness of melanoma cells, which raises the possible adverse effect of sildenafil use on melanoma risk. OBJECTIVE To evaluate the association between sildenafil use and risk of incident melanoma among men in the United States. DESIGN, SETTING, AND PARTICIPANTS Our study is a prospective cohort study. In 2000, participants in the Health Professionals' Follow-up Study were questioned regarding sildenafil use for erectile dysfunction. Participants who reported cancers at baseline were excluded. A total of 25 848 men remained in the analysis. MAIN OUTCOMES AND MEASURES The incidence of skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), was obtained in the self-reported questionnaires biennially. The diagnosis of melanoma and SCC was pathologically confirmed. RESULTS We identified 142 melanoma, 580 SCC, and 3030 BCC cases during follow-up (2000-2010). Recent sildenafil use at baseline was significantly associated with an increased risk of subsequent melanoma with a multivariate-adjusted hazard ratio (HR) of 1.84 (95% CI, 1.04-3.22). In contrast, we did not observe an increase in risk of SCC (HR, 0.84; 95% CI, 0.59-1.20) or BCC (1.08; 0.93-1.25) associated with sildenafil use. Moreover, erectile function itself was not associated with an altered risk of melanoma. Ever use of sildenafil was also associated with a higher risk of melanoma (HR, 1.92; 95% CI, 1.14-3.22). A secondary analysis excluding those reporting major chronic diseases at baseline did not appreciably change the findings; the HR of melanoma was 2.24 (95% CI, 1.05-4.78) for sildenafil use at baseline and 2.77 (1.32-5.85) for ever use. CONCLUSIONS AND RELEVANCE Sildenafil use may be associated with an increased risk of developing melanoma. Although this study is insufficient to alter clinical recommendations, we support a need for continued investigation of this association. C1 [Li, Wen-Qing; Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Li, Wen-Qing; Qureshi, Abrar A.] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Dermatol, Providence, RI 02903 USA. [Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Network Med,Dept Med, Boston, MA 02115 USA. [Robinson, Kathleen C.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Robinson, Kathleen C.] Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Boston, MA USA. [Han, Jiali] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Han, Jiali] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46202 USA. [Han, Jiali] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46202 USA. [Han, Jiali] Tianjin Med Univ, Canc Inst & Hosp, Dept Epidemiol, Tianjin, Peoples R China. RP Han, JL (reprint author), Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, 714 N Senate Ave, Indianapolis, IN 46202 USA. EM jialhan@iu.edu RI Li, Wenqing/N-2293-2014 OI Li, Wenqing/0000-0002-1283-4091 FU National Institutes of Health [P01 CA055075] FX The HPFS is partly supported by grant P01 CA055075 from the National Institutes of Health. NR 38 TC 25 Z9 27 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUN PY 2014 VL 174 IS 6 BP 964 EP 970 DI 10.1001/jamainternmed.2014.594 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA AI4OA UT WOS:000336843500033 PM 24710960 ER PT J AU Wiener, RS Gould, MK Slatore, CG Fincke, BG Schwartz, LM Woloshin, S AF Wiener, Renda Soylemez Gould, Michael K. Slatore, Christopher G. Fincke, Benjamin G. Schwartz, Lisa M. Woloshin, Steven TI Resource Use and Guideline Concordance in Evaluation of Pulmonary Nodules for Cancer Too Much and Too Little Care SO JAMA INTERNAL MEDICINE LA English DT Article ID FLEISCHNER SOCIETY GUIDELINES; LUNG-CANCER; MANAGEMENT; RADIOLOGISTS; CT; COMPLICATIONS; STATEMENT; ADHERENCE; BIOPSY; FRANCE AB IMPORTANCE Pulmonary nodules are common, and more will be found with implementation of lung cancer screening. How potentially malignant pulmonary nodules are evaluated may affect patient outcomes, health care costs, and effectiveness of lung cancer screening programs. Guidelines for evaluating pulmonary nodules for cancer exist, but little is known about how nodules are evaluated in the usual care setting. OBJECTIVE To characterize nodule evaluation and concordance with guidelines. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted including detailed review of medical records from pulmonary nodule detection through evaluation completion, cancer diagnosis, or study end (December 31, 2012). The participants included 300 adults with pulmonary nodules from 15 Veterans Affairs hospitals. MAIN OUTCOMES AND MEASURES Resources used for evaluation at any Veterans Affairs facility and guideline-concordant evaluation served as the main outcomes. RESULTS Twenty-seven of 300 patients (9.0%) with pulmonary nodules ultimately received a diagnosis of lung cancer: 1 of 57 (1.8%) with a nodule of 4 mm or less, 4 of 134 (3.0%) with a nodule of 5 to 8 mm, and 22 of 109 (20.2%) with a nodule larger than 8 mm. Nodule evaluation entailed 1044 imaging studies, 147 consultations, 76 biopsies, 13 resections, and 21 hospitalizations. Radiographic surveillance (n = 277) lasted a median of 13 months but ranged from less than 0.5 months to 8.5 years. Forty-six patients underwent invasive procedures (range per patient, 1-4): 41.3%(19 patients) did not have cancer and 17.4% (8) experienced complications, including 1 death. Notably, 15 of the 300 (5.0%) received no purposeful evaluation and had no obvious reason for deferral, seemingly "falling through the cracks." Among 197 patients with a nodule detected after release of the Fleischner Society guidelines, 44.7% received care inconsistent with guidelines (17.8% overevaluation, 26.9% underevaluation). In multivariable analyses, the strongest predictor of guideline-inconsistent care was inappropriate radiologist recommendations (overevaluation relative risk, 4.6 [95% CI, 2.3-9.2]; underevaluation, 4.3 [2.7-6.8]). Other systems factors associated with underevaluation included receiving care at more than 1 facility (2.0 [1.5-2.7]) and nodule detection during an inpatient or preoperative visit (1.6 [1.1-2.5]). CONCLUSIONS AND RELEVANCE Pulmonary nodule evaluation is often inconsistent with guidelines, including cases with no workup and others with prolonged surveillance or unneeded procedures that may cause harm. Systems to improve quality (eg, aligning radiologist recommendations with guidelines and facilitating communication across providers) are needed before lung cancer screening is widely implemented. C1 [Wiener, Renda Soylemez; Fincke, Benjamin G.] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, Bedford, MA 01730 USA. [Wiener, Renda Soylemez] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Wiener, Renda Soylemez; Schwartz, Lisa M.; Woloshin, Steven] Dartmouth Med Sch, Dartmouth Inst Hlth Policy & Clin Practice, Hanover, NH USA. [Gould, Michael K.] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA. [Slatore, Christopher G.] Portland VA Med Ctr, Hlth Serv Res & Dev, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Fincke, Benjamin G.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Schwartz, Lisa M.; Woloshin, Steven] Dept Vet Affairs, Vet Affairs Outcomes Grp, White River Jct, VT USA. RP Wiener, RS (reprint author), Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Bldg 70 Mail Code 152, Bedford, MA 01730 USA. EM rwiener@bu.edu OI Wiener, Renda/0000-0001-7712-2135; Slatore, Christopher/0000-0003-0958-8122 FU Veterans Affairs (VA) Health Services Research and Development (HSRD) [PPO 08-401]; White River Junction VA Medical Center; Edith Nourse Rogers Memorial Veterans Hospital; Portland VA Medical Center; National Cancer Institute [K07 CA138772]; VA HSR&D Career Development Award FX This study was supported by the Veterans Affairs (VA) Health Services Research and Development (HSR&D) (PPO 08-401) and with resources from the White River Junction VA Medical Center, Edith Nourse Rogers Memorial Veterans Hospital, and Portland VA Medical Center. Dr Wiener is also supported by career development award K07 CA138772 from the National Cancer Institute, and Dr Slatore is supported by a VA HSR&D Career Development Award. NR 37 TC 20 Z9 20 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 JUN PY 2014 VL 174 IS 6 DI 10.1001/jamainternmed.2014.561 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AI4OA UT WOS:000336843500017 PM 24710850 ER PT J AU van Deursen, VM Edwards, C Cotter, G Davison, BA Damman, K Teerlink, JR Metra, M Felker, GM Ponikowski, P Unemori, E Severin, T Voors, AA AF van Deursen, Vincent M. Edwards, Christopher Cotter, Gad Davison, Beth A. Damman, Kevin Teerlink, John R. Metra, Marco Felker, G. Michael Ponikowski, Piotr Unemori, Elaine Severin, Thomas Voors, Adriaan A. TI Liver Function, In-Hospital, and Post-Discharge Clinical Outcome in Patients With Acute Heart Failure-Results From the Relaxin for the Treatment of Patients With Acute Heart Failure Study SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Liver function; acute decompensated heart failure; prognosis ID FUNCTION TESTS; FUNCTION ABNORMALITIES; MORTALITY; PROGRAM AB Background: Elevated plasma concentrations of liver function tests are prevalent in patients with chronic heart failure (HF). Little is known about liver function in patients with acute HF. We aimed to assess the prevalence and prognostic value of serial measurements of liver function tests in patients admitted with acute decompensated HF. Methods: We investigated liver function tests from all 234 patients from the Relaxin for the Treatment of Patients With Acute Heart Failure study at baseline and during hospitalization. The end points were worsening HF through day 5, 60-day mortality or rehospitalization, and 180-day mortality. Results: Mean age was 70 +/- 10 years, 56% were male, and most patients were in New York Heart Association functional class III/IV (73%). Abnormal liver function tests were frequently found. for alanine transaminase (ALT; 12%), aspartate transaminase (AST; 21%), alkaline phosphatase (12%), and total bilirubin (19%), and serum albumin (25%) and total protein (9%) were decreased. In-hospital changes were very small. On a continuous scale, baseline ALT and AST were associated with 180-day mortality (hazard ratios [HRs; per doubling] 1.52 [P = .030] and 1.97 [P = .013], respectively) and worsening HF through day 5 (HRs [per doubling] 1.72 [P = .005] and 1.95 [P = .008], respectively). Albumin was associated with 180-day mortality (HR 0.86; P = .001) but not with worsening HF (HR 0.95; P = .248). Total protein was associated with only worsening HF (HR 0.91; P = .004). Conclusions: Abnormal liver function tests are often present in patients with acute HF and are associated with an increased risk for mortality, rehospitalization, and in-hospital worsening HF. C1 [van Deursen, Vincent M.; Damman, Kevin; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Edwards, Christopher; Cotter, Gad; Davison, Beth A.] Momentum Res, Durham, NC USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94143 USA. [Metra, Marco] Univ Brescia, Dept Expt & Appl Sci, Sect Cardiovasc Dis, Brescia, Italy. [Felker, G. Michael] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Ponikowski, Piotr] Med Univ, Dept Hlth Sci, Mil Hosp, Dept Cardiol, Wroclaw, Poland. [Unemori, Elaine] Corthera, San Mateo, CA USA. [Severin, Thomas] Novartis Pharmaceut, Basel, Switzerland. RP Voors, AA (reprint author), Univ Med Ctr Groningen, Dept Cardiol, Hanzepl 1, NL-9700 RB Groningen, Netherlands. EM a.a.voors@umcg.nl RI Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Davison, Beth/0000-0003-2374-6449; Metra, Marco/0000-0001-6691-8568 FU Corthera (a Novartis affiliate company); Amgen; Bayer; Corthera; Cardio3 Bioscience; Cytokinetics; Merck; Novartis; Takeda; Teva; Trevena; Abbott Vascular; Medpace; Otsuka; Roche Diagnostics; BG Medicine; Medtronic; St Jude; National Heart, Lung, and Blood Institute; Abbott; PDL Biopharma; Alere; Cardio3 Biosciences; Celladon; Ceva; European Commission; Dutch Heart Foundation; Servier; Torrent; Vifor FX The Pre-RELAX-AHF study is supported by Corthera (a Novartis affiliate company). Mr Edwards and Drs Cotter and Davison are employees of Momentum Research, which has provided consulting and trial management services to Novacardia, Merck, Corthera, Novartis, Nile Therapeutics, Bioheart, Cardio3 Biosciences, Amgen, Celadon, Targegen, Trevena, Sorbent Therapeutics, and the National Institutes of Health. Dr Teerlink has received research grants or consulting fees from Amgen, Bayer, Corthera, Cardio3 Bioscience, Cytokinetics, Merck, Novartis, Takeda, Teva, and Trevena. Dr Metra has received consulting income from Abbott Vascular, Bayer, Corthera, and Novartis and travel support and honoraria from Servier and Novartis. Dr Felker has received consulting income from Novartis, Medpace, Amgen, Otsuka, Trevena, Roche Diagnostics, Merck, BG Medicine, Medtronic, and St Jude and grant funding from Amgen, Otsuka, Roche Diagnostics, and the National Heart, Lung, and Blood Institute. Dr Ponikowski has been a consultant for Astellas, Bayer, EKR Therapeutics, Johnson and Johnson, The Medicines Company, Medtronic, Novartis, Otsuka, Palatin Technologies, PDL Biopharma, Pericor Therapeutics, Sigma Tau, Solvay Pharmaceuticals, and Trevena; has received honoraria from Alere, Beckman-Coulter, Biogenidec, Corthera, Ikaria, Nile Therapeutics, Momentum Research, and Overcome; has received research support from Abbott, Merck and PDL Biopharma; and has received travel support from My Life and equipment support from Sonosite. Dr Unemori is employed by the sponsor, Corthera. Dr Severin is an employee and shareholder of Novartis Pharma. Dr Voors has received consultancy fees and/or research grants from Alere, Bayer, Cardio3 Biosciences, Celladon, Ceva, the European Commission, the Dutch Heart Foundation, Novartis, Servier, Torrent, and Vifor. Dr van Deursen no relationships relevant to the contents of this paper to disclose. NR 18 TC 10 Z9 10 U1 0 U2 3 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 JUN PY 2014 VL 20 IS 6 BP 407 EP 413 DI 10.1016/j.cardfail.2014.03.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI7LA UT WOS:000337070900005 PM 24642379 ER PT J AU Simonsen, CZ Sorensen, LH Karabegovic, S Mikkelsen, IK Schmitz, ML Juul, N Yoo, AJ Andersen, G AF Simonsen, Claus Z. Sorensen, Leif H. Karabegovic, Sanja Mikkelsen, Irene K. Schmitz, Marie L. Juul, Niels Yoo, Albert J. Andersen, Grethe TI MRI before intraarterial therapy in ischemic stroke: feasibility, impact, and safety SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE acute stroke; diffusion-weighted imaging; endovascular therapy; magnetic resonance imaging; outcome; selection ID ENDOVASCULAR TREATMENT; TRIAL; THROMBOLYSIS; SELECTION; DIFFUSION; COHORT; REVASCULARIZATION AB Intraarterial therapy (IAT) in acute ischemic stroke is effective for opening occlusions of major extracranial or intracranial vessels. Clinical efficacy data are lacking pointing to a need for proper patient selection. We examined feasibility, clinical impact, and safety profile of magnetic resonance imaging (MRI) for patient selection before IAT. In this single-center study, we collected epidemiologic, imaging, and outcome data on all intraarterial-treated patients presenting with anterior circulation occlusions at our center from 2004 to 2011. Magnetic resonance imaging was the first imaging choice. Computer tomography (CT) was performed in the presence of a contraindication. We treated 138 patients. Mean age was 64 years and median National Institutes of Health Stroke Scale (NIHSS) was 17. Major reperfusion (thrombolysis in cerebral infarction (TICI) 2b + 3) was achieved in 52% and good outcome defined as modified Rankin Scale (mRS) score 0 to 2 at 90 days was achieved in 41%. Mortality at 90 days was 10%. There was only one symptomatic hemorrhage. Recanalization, age, and stroke severity were associated with outcome. Preprocedure MRI was obtained in 83%. Good outcome was significantly associated with smaller diffusion-weighted imaging (DWI) lesion size at presentation and not with the size of the perfusion lesion. It is feasible to triage patients for IAT using MRI with acceptable rates of poor outcome and symptomatic hemorrhage. C1 [Simonsen, Claus Z.; Schmitz, Marie L.; Andersen, Grethe] Aarhus Univ Hosp, Dept Neurol, DK-8000 Aarhus C, Denmark. [Sorensen, Leif H.; Karabegovic, Sanja] Aarhus Univ Hosp, Dept Neuroradiol, DK-8000 Aarhus C, Denmark. [Mikkelsen, Irene K.] Aarhus Univ, Ctr Funct Integrat Neurosci, Aarhus, Denmark. [Juul, Niels] Aarhus Univ Hosp, Dept Neuroanaestesiol, DK-8000 Aarhus C, Denmark. [Yoo, Albert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Diagnost & Intervent Neuroradiol, Boston, MA 02115 USA. RP Simonsen, CZ (reprint author), Aarhus Univ Hosp, Dept Neurol, Norrebrogade 44, DK-8000 Aarhus C, Denmark. EM clasim@rm.dk RI Demchuk, Andrew/E-1103-2012 OI Demchuk, Andrew/0000-0002-4930-7789 FU Penumbra Inc.; Remedy Pharmaceuticals Inc. FX AJY has received research support from Penumbra Inc. and Remedy Pharmaceuticals Inc. Also honorarium from Codman. The remaining authors have no conflict of interest. NR 27 TC 6 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUN PY 2014 VL 34 IS 6 BP 1076 EP 1081 DI 10.1038/jcbfm.2014.57 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA AI4JH UT WOS:000336831000019 PM 24690941 ER PT J AU Bauer, CA Kim, EY Marangoni, F Carrizosa, E Claudio, NM Mempel, TR AF Bauer, Christian A. Kim, Edward Y. Marangoni, Francesco Carrizosa, Esteban Claudio, Natalie M. Mempel, Thorsten R. TI Dynamic Treg interactions with intratumoral APCs promote local CTL dysfunction SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID REGULATORY T-CELLS; DRAINING LYMPH-NODES; ANTIGEN-SPECIFIC CD8; EFFECTOR FUNCTION; DENDRITIC CELLS; TUMOR MICROENVIRONMENT; MELANOMA PATIENTS; INFLAMED TISSUES; THYMIC SELECTION; IN-VITRO AB Tregs control various functions of effector T cells; however, where and how Tregs exert their immunomodulatory effects remain poorly understood. Here we developed a murine model of adoptive T cell therapy and found that Tregs induce a dysfunctional state in tumor-infiltrating CTLs that resembles T cell exhaustion and is characterized by low expression of effector cytokines, inefficient cytotoxic granule release, and coexpression of coinhibitory receptors PD-1 and TIM-3. Induction of CTL dysfunction was an active process, requiring local TCR signals in tumor tissue. Tregs infiltrated tumors only subsequent to Ag-dependent activation and expansion in tumor-draining LNs; however, Tregs also required local Ag reencounter within tumor tissue to induce CTL dysfunction and prevent tumor rejection. Multiphoton intravital microscopy revealed that in contrast to CTLs, Tregs only rarely and briefly interrupted their migration in tumor tissue in an Ag-dependent manner and formed unstable tethering-interactions with CD11c(+) APCs, coinciding with a marked reduction of CD80 and CD86 on APCs. Activation of CTLs by Treg-conditioned CD80/86(lo) DCs promoted enhanced expression of both TIM-3 and PD-1. Based on these data, we propose that Tregs locally change the costimulatory landscape in tumor tissue through transient, Ag-dependent interactions with APCs, thus inducing CTL dysfunction by altering the balance of costimulatory and coinhibitory signals these cells receive. C1 [Bauer, Christian A.; Kim, Edward Y.; Marangoni, Francesco; Carrizosa, Esteban; Claudio, Natalie M.; Mempel, Thorsten R.] Harvard Univ, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis,Sch Med, Boston, MA USA. RP Mempel, TR (reprint author), Massachusetts Gen Hosp East, 149 Thirteenth St,Room 8301, Boston, MA 02129 USA. EM tmempel@mgh.harvard.edu RI Marangoni, Francesco/I-9087-2012 OI Marangoni, Francesco/0000-0002-2490-849X FU NIH [AI073457, CA150975, CA179563]; German Research Foundation [BA 3824/1-1]; Fellowship from the Terry Fox Foundation (Canadian Cancer Society Research Institute) [19726]; Dana Foundation. FX We thank Ulrich von Andrian and James Moon for critical reading of the manuscript and helpful comments, and Sean Megason and Jeff Hogan for the pCS-H2B-Cerulean and pcDNA3.1-HA constructs, respectively. T.R. Mempel was supported by NIH grants AI073457, CA150975, and CA179563 and by a grant by the Dana Foundation. C.A. Bauer was supported by a grant from the German Research Foundation (BA 3824/1-1). E.Y. Kim was supported by a Fellowship from the Terry Fox Foundation (Canadian Cancer Society Research Institute award no. 19726). NR 73 TC 34 Z9 34 U1 0 U2 17 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 JUN PY 2014 VL 124 IS 6 BP 2425 EP 2440 DI 10.1172/JCI66375 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI4XC UT WOS:000336868800019 PM 24812664 ER PT J AU Davidowitz, RA Selfors, LM Iwanicki, MP Elias, KM Karst, A Piao, HY Ince, TA Drage, MG Dering, J Konecny, GE Matulonis, U Mills, GB Slamon, DJ Drapkin, R Brugge, JS AF Davidowitz, Rachel A. Selfors, Laura M. Iwanicki, Marcin P. Elias, Kevin M. Karst, Alison Piao, Huiying Ince, Tan A. Drage, Michael G. Dering, Judy Konecny, Gottfried E. Matulonis, Ursula Mills, Gordon B. Slamon, Dennis J. Drapkin, Ronny Brugge, Joan S. TI Mesenchymal gene program-expressing ovarian cancer spheroids exhibit enhanced mesothelial clearance SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CARCINOMA ASCITES SPHEROIDS; ADVANCED EPITHELIAL OVARIAN; IN-VITRO; CELL MONOLAYERS; FALLOPIAN-TUBE; PERITONEAL METASTASIS; EXTRACELLULAR-MATRIX; TUMOR-CELLS; E-CADHERIN; TRANSITION AB Metastatic dissemination of ovarian tumors involves the invasion of tumor cell clusters into the mesothelial cell lining of peritoneal cavity organs; however, the tumor-specific factors that allow ovarian cancer cells to spread are unclear. We used an in vitro assay that models the initial step of ovarian cancer metastasis, clearance of the mesothelial cell layer, to examine the clearance ability of a large panel of both established and primary ovarian tumor cells. Comparison of the gene and protein expression profiles of clearance-competent and clearance-incompetent cells revealed that mesenchymal genes are enriched in tumor populations that display strong clearance activity, while epithelial genes are enriched in those with weak or undetectable activity. Overexpression of transcription factors SNAI1, TWIST1, and ZEB1, which regulate the epithelial-to-mesenchymal transition (EMT), promoted mesothelial clearance in cell lines with weak activity, while knockdown of the EMT-regulatory transcription factors TWIST1 and ZEB1 attenuated mesothelial clearance in ovarian cancer cell lines with strong activity. These fmdings provide important insights into the mechanisms associated with metastatic progression of ovarian cancer and suggest that inhibiting pathways that drive mesenchymal programs may suppress tumor cell invasion of peritoneal tissues. C1 [Davidowitz, Rachel A.; Selfors, Laura M.; Iwanicki, Marcin P.; Brugge, Joan S.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Elias, Kevin M.; Karst, Alison; Piao, Huiying; Matulonis, Ursula; Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Elias, Kevin M.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. [Ince, Tan A.] Univ Miami, Miller Sch Med, Braman Family Breast Canc Inst, Interdisciplinary Stem Cell Inst,Dept Pathol, Miami, FL 33136 USA. [Ince, Tan A.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Drage, Michael G.; Drapkin, Ronny] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Dering, Judy; Konecny, Gottfried E.; Slamon, Dennis J.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Los Angeles, CA 90095 USA. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM ronny_drapkin@dfci.harvard.edu; Joan_Brugge@hms.harvard.edu RI Drapkin, Ronny/E-9944-2016; OI Drapkin, Ronny/0000-0002-6912-6977; Elias, Kevin/0000-0003-1502-5553 FU Ovarian Cancer Research Fund; Honorable Tina Brozman Foundation; Gamel. Family Ovarian Cancer Research Fund; Dana-Farber Cancer Institute; NIH [CA016672] FX We would like to thank Yiling Lu and Doris Siwak (MD Anderson Cancer Center) for performing the RPPA studies; Jennifer Waters and the Nikon Imaging Center at Harvard Medical School for support on the microscopy studies; and Kong-Jie Kah and Robert Weinberg for donation of the ZEB1 overexpression construct. We also thank Ghassan Mouneimne for review of the manuscript and helpful discussions and Grace Gao for lab management. These studies were supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to J.S. Brugge and R. Drapkin), the Ovarian Cancer Research Fund (to R. Drapkin), the Honorable Tina Brozman Foundation (to R. Drapkin), the Robert and Debra First Fund (to R. Drapkin), the Gamel. Family Ovarian Cancer Research Fund (to R. Drapkin), the Susan F. Smith Center for Women's Cancers at the Dana-Farber Cancer Institute (to R. Drapkin), and the Men's Collaborative to Cure Women's Cancer (to J.S. Brugge and R. Drapkin). RPPA was performed at the MD Anderson RPPA Core Facility (supported by NIH grant CA016672). NR 63 TC 25 Z9 25 U1 1 U2 3 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 JUN PY 2014 VL 124 IS 6 BP 2611 EP 2625 DI 10.1172/JCI69815 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA AI4XC UT WOS:000336868800034 PM 24762435 ER PT J AU Misra, M Klibanski, A AF Misra, Madhusmita Klibanski, Anne TI Anorexia nervosa and bone SO JOURNAL OF ENDOCRINOLOGY LA English DT Review DE anorexia nervosa; eating disorders; adolescents; adults; bone density; microarchitecture; strength; fracture; growth hormone; IGF1; estrogen; testosterone; bisphosphonates; leptin; ghrelin; PYY; adipokines ID DWELLING ADOLESCENT GIRLS; PREADIPOCYTE FACTOR-I; BROWN ADIPOSE-TISSUE; MINERAL DENSITY; GROWTH-HORMONE; YOUNG-WOMEN; HEALTHY ADOLESCENTS; SECRETORY DYNAMICS; EATING-DISORDERS; BULIMIA-NERVOSA AB Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure, and reduced bone strength, all of which contribute to increased fracture risk. Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising additional concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, and hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen-progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiological estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age, given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN. C1 [Misra, Madhusmita; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita; Klibanski, Anne] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediatr Endocrine Unit, Boston, MA 02114 USA. RP Misra, M (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457,55 Fruit St, Boston, MA 02114 USA. EM mmisra@partners.org FU NIH [1 R01 HD060827, 5 UL1 RR025758, K24HD071843, 2 R01 DK062249] FX This work was supported in part by NIH grants 1 R01 HD060827, 5 UL1 RR025758, K24HD071843, and 2 R01 DK062249. NR 92 TC 24 Z9 24 U1 1 U2 8 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 EI 1479-6805 J9 J ENDOCRINOL JI J. Endocrinol. PD JUN PY 2014 VL 221 IS 3 BP R163 EP R176 DI 10.1530/JOE-14-0039 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI7WF UT WOS:000337111400007 PM 24898127 ER PT J AU Doring, AC Nota, SPFT Hageman, MGJS Ring, DC AF Doering, Anne-Carolin Nota, Sjoerd P. F. T. Hageman, Michiel G. J. S. Ring, David C. TI Measurement of Upper Extremity Disability Using the Patient-Reported Outcomes Measurement Information System SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE PROMIS; QuickDASH; upper extremity disability; outcome questionnaires ID COMPUTERIZED ADAPTIVE TESTS; FUNCTION ITEM BANK; PRIMARY-CARE; PROMIS; QUESTIONNAIRE; VALIDITY; PAIN; RESPONSIVENESS; RELIABILITY; QUICKDASH AB Purpose Current questionnaires used to measure upper extremity specific disability can be time-consuming and subject to ceiling effects. The National Institutes of Health developed Patient-Reported Outcomes Measurement Information System (PROMIS) measures based on computer adaptive testing (CAT), a technique that is more efficient and less subject to floor and ceiling effects than traditional questionnaires with a fixed number of,questions. This study tested the correlation of the Physical Function-Upper Extremity CAT with the Quick-Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire. Methods Patients presenting to our orthopedic outpatient clinic were invited to participate in this observational cross-sectional study between August and October 2013. A study sample of 84 patients completed the QuickDASH and PROMIS Physical Function-Upper Extremity CAT, and 3 other PROMIS measures, as well as the 2-question Pain Self-efficacy Questionnaire and the 2-question Patient Health Questionnaire. Results A strong correlation was found between QuickDASH and PROMIS Physical Function-Upper Extremity CAT, with a significantly shorter completion time for the latter. Conclusions We recommend the PROMIS Upper Extremity CAT because it is valid, reliable, and easy to use, and it provides easy reference to population norms (a score of 50 represents the norm in the United States population, and every 10 points represents a standard deviation from the norm). Copyright (C) 2014 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Doering, Anne-Carolin; Nota, Sjoerd P. F. T.; Hageman, Michiel G. J. S.; Ring, David C.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, DC (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 24 TC 13 Z9 13 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 JUN PY 2014 VL 39 IS 6 BP 1160 EP 1165 DI 10.1016/j.jhsa.2014.03.013 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AI6TX UT WOS:000337011000021 PM 24799143 ER PT J AU Menendez, ME Ring, D AF Menendez, Mariano E. Ring, David TI Disability Versus Impairment SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter ID GRIP STRENGTH; FRACTURES; OUTCOMES C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. NR 5 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 JUN PY 2014 VL 39 IS 6 BP 1231 EP 1231 DI 10.1016/j.jhsa.2014.02.036 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AI6TX UT WOS:000337011000036 PM 24862121 ER PT J AU Menendez, ME Ring, D AF Menendez, Mariano E. Ring, David TI de Quervain Tendinopathy: "Success" and Other Subtleties SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter C1 [Menendez, Mariano E.; Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Menendez, ME (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. OI Ring, David/0000-0002-6506-4879 NR 3 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 JUN PY 2014 VL 39 IS 6 BP 1232 EP 1233 DI 10.1016/j.jhsa.2014.03.023 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AI6TX UT WOS:000337011000038 PM 24862123 ER PT J AU Kim, BYS Jiang, W Beiko, J Prabhu, SS DeMonte, F Gilbert, MR Sawaya, R Aldape, KD Cahill, DP McCutcheon, IE AF Kim, Betty Y. S. Jiang, Wen Beiko, Jason Prabhu, Sujit S. DeMonte, Franco Gilbert, Mark R. Sawaya, Raymond Aldape, Kenneth D. Cahill, Daniel P. McCutcheon, Ian E. TI Diagnostic discrepancies in malignant astrocytoma due to limited small pathological tumor sample can be overcome by IDH1 testing SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioblastoma; Anaplastic astrocytoma; Malignant astrocytoma; Diagnosis; Surgical resection; Isocitrate dehydrogenase ID ANAPLASTIC GLIOMAS; DIFFUSE GLIOMA; MUTATION; CLASSIFICATION; GLIOBLASTOMA; LIMITATIONS; BIOPSY; MANAGEMENT; FRAMELESS; PROGNOSIS AB The accurate grading of malignant astrocytomas has significant prognostic and therapeutic implications. Traditional histopathological grading can be challenging due to regional tumor heterogeneity, especially in scenarios where small amounts of tissue are available for pathologic review. Here, we hypothesized that a critical tumor resection volume is needed for correct grading of astrocytomas by histopathology. For insufficient tissue sampling, IDH1 molecular testing can act as a complementary marker to improve diagnostic accuracy. Volumetric analyses were obtained using preoperative and postoperative MRI images. Histological specimens were gathered from 403 patients with malignant astrocytoma who underwent craniotomy. IDH1 status was assessed by immunohistochemistry and sequencing. Patients with > 20 cubic centimeters (cc) of the total tumor volume resected on MRI have higher rate of GBM diagnosis compared to < 20 cc [odds ratio (OR) 2.57, 95 % confidence interval (CI) 1.6-4.06, P < 0.0001]. The rate of IDH1 status remained constant regardless of the tumor volume resected (OR 0.81, 95 % CI 0.48-1.36, P < 0.43). The rate of GBM diagnosis is twofold greater for individual surgical specimen > 10 cc than those of lower volume (OR 2.48, 95 % CI 1.88-3.28, P < 0.0001). Overall survival for AA patients with > 20 cc tumor resection on MRI is significantly better than those with < 20 cc tumor resected (P < 0.05). No volume-dependent differences were observed in patients with GBM (P < 0.4), IDH1 wild type (P < 0.1) or IDH1 mutation (P < 0.88). IDH1 status should be considered when total resection volume is < 20 cc based on MRI analysis and for surgical specimen < 10 cc to complement histopathologic diagnosis of malignant astrocytomas. In these specimens, under-diagnosis of GBM may occur when analysis is restricted to histopathology alone. C1 [Kim, Betty Y. S.; Prabhu, Sujit S.; DeMonte, Franco; Sawaya, Raymond; McCutcheon, Ian E.] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. [Jiang, Wen] Stanford Sch Med, Stanford, CA 94305 USA. [Beiko, Jason] Univ Manitoba, Dept Neurosurg, Winnipeg, MB R3E 3P5, Canada. [Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Aldape, Kenneth D.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Cahill, Daniel P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Kim, BYS (reprint author), Mayo Clin, Coll Med, Dept Neurosurg, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM kim.betty@mayo.edu; imccutch@mdanderson.org RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; Cahill, Daniel/0000-0003-2552-6546; Jiang, Wen/0000-0001-9154-633X FU Detweiler Travelling Fellowship from the Royal College of Physicians and Surgeons of Canada; James and Sarah Kennedy Mayo Clinic Research Career Development Award; Burroughs-Wellcome Career Award in Medical Sciences; James S. McDonnell Foundation FX The authors also wish to thank Dr. Dima Suki for helpful discussions related to statistical analysis. Financial support was provided by the Detweiler Travelling Fellowship from the Royal College of Physicians and Surgeons of Canada and James and Sarah Kennedy Mayo Clinic Research Career Development Award (B. Y. S. K.), Burroughs-Wellcome Career Award in Medical Sciences and James S. McDonnell Foundation (D. P. C.). NR 32 TC 6 Z9 6 U1 0 U2 2 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 JUN PY 2014 VL 118 IS 2 BP 405 EP 412 DI 10.1007/s11060-014-1451-0 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AI6YN UT WOS:000337024300022 PM 24777756 ER PT J AU Alvarez, V Crary, J Slick, N Fry, B Stein, T McKee, A AF Alvarez, Victor Crary, John Slick, Nathalie Fry, Brian Stein, Thor McKee, Ann TI Opthalmological Abnormalities in CTE SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [Alvarez, Victor; Slick, Nathalie; Fry, Brian] Boston Univ, Sch Med, Boston, MA 02215 USA. [Stein, Thor; McKee, Ann] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 24 BP 591 EP 591 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100034 ER PT J AU Rose, M Rashid, A Jakobiec, F AF Rose, Matthew Rashid, Alia Jakobiec, Frederick TI Intraocular Medulloepitheliomas in Children and Adults show Markers of Retinal Development and Glioneuronal Differentiation SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [Rose, Matthew] Harvard, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Rashid, Alia; Jakobiec, Frederick] Harvard, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 23 BP 591 EP 591 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100033 ER PT J AU William, C Saqran, L Stern, M Frosch, M Hyman, B AF William, Christopher Saqran, Lubna Stern, Matthew Frosch, Matthew Hyman, Bradley TI Developmental Synaptic Plasticity Defects in a Mouse Model of Down Syndrome SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [William, Christopher; Frosch, Matthew] Massachusetts Gen Hosp, Neuropathol Serv, Boston, MA 02114 USA. [Saqran, Lubna; Stern, Matthew] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hyman, Bradley] MGH, MassGen Inst Neurodegenerat Dis, 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 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 32 BP 593 EP 594 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100042 ER PT J AU McGuone, D Shapiro, K Staley, K Stemmer-Rachamimov, A AF McGuone, Declan Shapiro, Kevin Staley, Kevin Stemmer-Rachamimov, Anat TI Lack of Findings to Support a Role for HPV in a Cohort of Focal Cortical Dysplasia, Type IIB SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [McGuone, Declan; Shapiro, Kevin; Staley, Kevin; Stemmer-Rachamimov, Anat] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 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 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 70 BP 603 EP 604 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100080 ER PT J AU McGuone, D Marciscano, A Niemierko, A Curry, W Barker, F Martuza, R Oh, K Loeffler, J Shih, H Stemmer-Rachamimov, A AF McGuone, Declan Marciscano, Ariel Niemierko, Andrzej Curry, William Barker, Fred, II Martuza, Robert Oh, Kevin Loeffler, Jay Shih, Helen Stemmer-Rachamimov, Anat TI WHO Grade I Meningiomas with Atypical Features: Correlation of Histopathology with Clinical Outcome SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [McGuone, Declan; Niemierko, Andrzej; Curry, William; Barker, Fred, II; Martuza, Robert; Oh, Kevin; Loeffler, Jay; Shih, Helen; Stemmer-Rachamimov, Anat] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. [Marciscano, Ariel] Johns Hopkins Univ Hosp, Baltimore, MD 21287 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 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 86 BP 607 EP 608 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100096 ER PT J AU Suva, M Patel, A Bernstein, B Louis, D AF Suva, Mario Patel, Anoop Bernstein, Bradley Louis, David TI Reprogramming Cell Circuits in Glioblastoma SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [Suva, Mario; Patel, Anoop; Bernstein, Bradley; Louis, David] Massachusetts Gen Hosp, Boston, MA 02114 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 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 108 BP 613 EP 614 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100118 ER PT J AU Davidson, C Liu, CH Vitte, J Giovannini, M McClatchey, A AF Davidson, Christian Liu, Ching-Hui Vitte, Jeremie Giovannini, Marco McClatchey, Andrea TI Altered Receptor Tyrosine Kinase Regulation Promotes Growth Factor Adaptability in Nf2-mutant Schwann Cells SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [Davidson, Christian; Liu, Ching-Hui; McClatchey, Andrea] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vitte, Jeremie; Giovannini, Marco] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RI Vitte, Jeremie/B-9874-2017 OI Vitte, Jeremie/0000-0002-2567-7988 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 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 117 BP 616 EP 616 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100128 ER PT J AU Mordes, D Suzuki, N Salameh, J Stewart, M Maroof, A Han, S Brown, R Eggan, K AF Mordes, Daniel Suzuki, Naoki Salameh, Johnny Stewart, Morag Maroof, Asif Han, Steve Brown, Robert Eggan, Kevin TI A Loss of Function Mutation in the C9ORF72 Mouse Ortholog Results in Motor System Degeneration SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-of-Neuropathologists-Inc CY JUN 12-15, 2014 CL Portland, OR SP Amer Assoc Neuropathologists Inc C1 [Mordes, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Suzuki, Naoki; Maroof, Asif] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Salameh, Johnny; Han, Steve; Brown, Robert] Univ Massachusetts, Sch Med, Dept Neurol, Amherst, MA 01003 USA. [Stewart, Morag] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Eggan, Kevin] Harvard Univ, HHMI, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 EI 1554-6578 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUN PY 2014 VL 73 IS 6 MA 132 BP 620 EP 620 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AI3AZ UT WOS:000336732100142 ER PT J AU Leger, PD Johnson, DH Robbins, GK Shafer, RW Clifford, DB Li, J McLaren, PJ Haas, DW AF Leger, Paul D. Johnson, Daniel H. Robbins, Gregory K. Shafer, Robert W. Clifford, David B. Li, Jun McLaren, Paul J. Haas, David W. TI Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384 SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE Peripheral neuropathy; HIV-1; Stavudine; Didanosine; Genomics ID MARIE-TOOTH-DISEASE; ANTIRETROVIRAL THERAPY; MUTATIONS; KIF1A AB Stavudine (d4T) was, until recently, one of the most widely prescribed antiretroviral drugs worldwide. While there has been a major shift away from d4T use in resource-limited countries, a large number of patients have previously received (or continue to receive) d4T, and many have developed peripheral neuropathy. The identification of genetic predictors of increased risk might suggest novel therapeutic targets for such patients. In AIDS Clinical Trials Group protocol 384, antiretroviral-naive patients were randomized to d4T/didanosine (ddI)-or zidovudine/lamivudine-containing regimens. Data from d4T/ddI recipients were analyzed for genome-wide associations (approximately 1 million genetic loci) with new onset distal sensory peripheral neuropathy. Analyses involved 254 patients (49 % White, 34 % Black, 17 % Hispanic), comprising 90 peripheral neuropathy cases (32 grade 1, 35 grade 2, 23 grade 3) and 164 controls. After correcting for multiple comparisons, no polymorphism was consistently associated with neuropathy among all patients, among White, Black, and Hispanic patients analyzed separately, both in genome-wide analyses (threshold, P<5.0x10(-8)) and focused on 46 neuropathy-associated genes (threshold, P<3.5x10(-5)). In the latter analyses, the lowest P values were in KIF1A among Whites (rs10199388, P= 8.4x10(-4)), in LITAF among Blacks (rs13333308, P= 6.0x10(-6)), and in NEFL among Hispanics (rs17763685, P= 5.6x10(-6)). Susceptibility to d4T/ddI-associated neuropathy is not explained by a single genetic variant with a marked effect. C1 [Leger, Paul D.; Johnson, Daniel H.; Haas, David W.] Vanderbilt Univ, Dept Med, Sch Med, Nashville, TN USA. [Robbins, Gregory K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Shafer, Robert W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Clifford, David B.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Clifford, David B.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Li, Jun] Vanderbilt Univ, Sch Med, Dept Neurol, Nashville, TN 37212 USA. [Li, Jun] VA Tennessee Valley Healthcare Syst, Nashville, TN USA. [McLaren, Paul J.] Ecole Polytech Fed Lausanne, Lausanne, Switzerland. [McLaren, Paul J.] Univ Lausanne, Univ Lausanne Hosp, Lausanne, Switzerland. [Haas, David W.] Vanderbilt Hlth One Hundred Oaks, Nashville, TN 37204 USA. RP Haas, DW (reprint author), Vanderbilt Hlth One Hundred Oaks, 719 Thompson Lane,Ste 47183, Nashville, TN 37204 USA. EM david.w.haas@vanderbilt.edu FU National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI-068636]; National Institute of Mental Health (NIMH); National Institute of Dental and Craniofacial Research (NIDCR); [AI-077505]; [AI-038858]; [AI-068634]; [AI038855]; [GM-80178]; [AI-062435]; [AI-069415]; [AI-069419]; [AI-069423]; [AI-069424]; [AI-069428]; [AI-069432]; [AI-069434]; [AI-069450]; [AI069452]; [AI-069465]; [AI-069471]; [AI-069472]; [AI-069474]; [AI-069477]; [AI-069484]; [AI-069495]; [AI-069501]; [AI-069502]; [AI-069511]; [AI069513]; [AI-069532]; [AI-069556]; [AI-25859]; [AI-27661]; [AI-34835]; [AI34853]; [AI-38844]; [AI-46370]; [AI-54999]; [AI-69467]; [AI-69495]; [AL32782]; [HL-087726]; [NS-059330]; [TR-000445] FX The authors are grateful to the many persons with HIV infection who volunteered for ACTG 384 and A5128. In addition, they acknowledge the contributions of study teams and site staff for protocols ACTG 384 and A5128. This project was supported by grant AI-077505 (DWH). The project described was also supported by award number U01 AI-068636 from the National Institute of Allergy and Infectious Diseases (NIAID) and supported by National Institute of Mental Health (NIMH) and National Institute of Dental and Craniofacial Research (NIDCR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. Additional grant support included AI-038858, AI-068634, AI038855, GM-80178, AI-062435, AI-069415, AI-069419, AI-069423, AI-069424, AI-069428, AI-069432, AI-069434, AI-069450, AI069452, AI-069465, AI-069471, AI-069472, AI-069474, AI-069477, AI-069484, AI-069495, AI-069501, AI-069502, AI-069511, AI069513, AI-069532, AI-069556, AI-25859, AI-27661, AI-34835, AI34853, AI-38844, AI-46370, AI-54999, AI-69467, AI-69495, AL32782, HL-087726, NS-059330, and TR-000445. NR 16 TC 4 Z9 4 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2014 VL 20 IS 3 BP 304 EP 308 DI 10.1007/s13365-014-0235-9 PG 5 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA AI3ZO UT WOS:000336804900010 PM 24554482 ER PT J AU Liu, PH Landrum, MB Weeks, JC Huskamp, HA Kahn, KL He, YL Mack, JW Keating, NL AF Liu, Pang-Hsiang Landrum, Mary Beth Weeks, Jane C. Huskamp, Haiden A. Kahn, Katherine L. He, Yulei Mack, Jennifer W. Keating, Nancy L. TI Physicians' Propensity To Discuss Prognosis Is Associated with Patients' Awareness of Prognosis for Metastatic Cancers SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID CELL LUNG-CANCER; COLORECTAL-CANCER; CHEMOTHERAPY; CARE; COMMUNICATION; PREFERENCES; SURVIVAL; METAANALYSIS; INFORMATION; PERCEPTIONS AB Background: Prognosis discussion is an essential component of informed decision-making. However, many terminally ill patients have a limited awareness of their prognosis and the causes are unclear. Objective: To explore the impact of physicians' propensity to discuss prognosis on advanced cancer patients' prognosis awareness. Design: Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) study, a prospective cohort study with patient and physician surveys. Setting/Subjects: We investigated 686 patients with metastatic lung or colorectal cancer at diagnosis who participated in the CanCORS study and reported about their life expectancy. Data were linked to the physician survey from 486 physicians who were identified by these patients as filling important roles in their cancer care. Results: Few patients with metastatic cancers (16.5%) reported an accurate awareness of their prognosis, defined as reporting a life expectancy of less than 2 years for lung cancer or less than 5 years for colorectal cancer. Patients whose most-important-doctor (in helping patient make decisions) reported discussing prognosis with terminally ill patients earlier were more likely than those whose doctors deferred these discussions to have an accurate prognosis awareness (adjusted proportion, 18.5% versus 7.6%; odds ratio, 3.23; 95% confidence interval, 1.39-7.52; p = 0.006). Conclusions: Few patients with advanced cancer could articulate an accurate prognosis estimate, despite most having received chemotherapy and many physicians reported they would discuss prognosis early. Physicians' propensity to discuss prognosis earlier was associated with more accurate patient reports of prognosis. Enhancing the communication skills of providers with important roles in cancer care may help to improve cancer patients' understanding of their prognosis. C1 [Liu, Pang-Hsiang; Landrum, Mary Beth; Huskamp, Haiden A.; He, Yulei; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Weeks, Jane C.; Mack, Jennifer W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kahn, Katherine L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Santa Monica, CA USA. [Kahn, Katherine L.] RAND Corp, Santa Monica, CA USA. [Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu RI Liu, Michael Pang-Hsiang/B-9903-2015 OI Liu, Michael Pang-Hsiang/0000-0001-8842-2264 FU National Cancer Institute [U01-CA093344]; Primary Data Collection and Research Centers (Dana-Farber Cancer Institute/Cancer Research Network) [U01-CA093332]; Primary Data Collection and Research Centers (Harvard Medical School/Northern California Cancer Center) [U01-CA093324]; Primary Data Collection and Research Centers (RAND/UCLA) [U01-CA093348]; Primary Data Collection and Research Centers (University of Alabama at Birmingham) [U01-CA093329]; Primary Data Collection and Research Centers (University of Iowa) [U01-CA093339]; Primary Data Collection and Research Centers (University of North Carolina) [U01-CA093326]; Department of Veteran's Affairs [CRS 02-164]; [1R01CH164021-01A1] FX This work of the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium was supported by the National Cancer Institute grants to the Statistical Coordinating Center (U01-CA093344) and Primary Data Collection and Research Centers (Dana-Farber Cancer Institute/Cancer Research Network U01-CA093332, Harvard Medical School/Northern California Cancer Center U01-CA093324, RAND/UCLA U01-CA093348, University of Alabama at Birmingham U01-CA093329, University of Iowa U01-CA093339, University of North Carolina U01-CA093326), and a Department of Veteran's Affairs grant to the Durham VA Medical Center CRS 02-164. The effort of Drs. Keating, Landrum, and Huskamp was also funded by 1R01CH164021-01A1. NR 27 TC 15 Z9 15 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2014 VL 17 IS 6 BP 673 EP U49 DI 10.1089/jpm.2013.0460 PG 11 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AI8HE UT WOS:000337151100009 PM 24742212 ER PT J AU Cooper, Z Corso, K Bernacki, R Bader, A Gawande, A Block, S AF Cooper, Zara Corso, Katherine Bernacki, Rachelle Bader, Angela Gawande, Atul Block, Susan TI Conversations about Treatment Preferences before High-Risk Surgery: A Pilot Study in the Preoperative Testing Center SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID CONTROLLED-TRIAL; DECISION-MAKING; FAMILY-MEMBERS; LIFE CARE; BUY-IN; END; DIRECTIVES; SUPPORT AB Background: It is important to engage patients and surrogates in conversations about goals and preferences for medical treatment before high-risk surgery. However, few interventions have been tested to facilitate these discussions. Objective: To assess the acceptability and feasibility of a facilitated, structured conversation with patients and surrogates about patient goals and preferences for medical treatment during their visit to a preoperative testing center before high-risk surgery. Design: A randomized controlled pilot study in the preoperative testing center at a tertiary academic hospital over a 4-month period. Measurements: We used baseline and preoperative surveys to assess feasibility, and to compare differences in worry, surrogate burden, and patient-surrogate concordance about treatment preferences in conversation and control groups. We assessed acceptability of the conversation qualitatively and through surveys. Results: Of 146 eligible patients, 79 were approached, and 65 declined to participate. Thirteen completed the study and 8 were randomized to the structured conversation. Major recruitment barriers included lack of time, or surrogate unavailability. Most postconversation patients were less worried, and more hopeful for a good recovery before surgery; 7 of 8 would recommend the conversation. Six of 8 surrogates reported postoperatively that the conversation helped prepare them to be a surrogate. Concordance improved in the intervention group only. Conclusions: Current processes of care present major barriers to conducting facilitated conversations in the preoperative testing center. Among a small group of patients and surrogates, most found a structured conversation about the patient's goals and preferences for medical treatment helpful before high-risk surgery. C1 [Cooper, Zara; Gawande, Atul] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Cooper, Zara; Corso, Katherine; Bader, Angela; Gawande, Atul] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Bader, Angela] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Bernacki, Rachelle; Block, Susan] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Gawande, Atul] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Cooper, Z (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM zcooper@partners.org FU Klarman Family Foundation FX Funding for this study was generously provided by the Klarman Family Foundation. NR 24 TC 7 Z9 7 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD JUN PY 2014 VL 17 IS 6 BP 701 EP 707 DI 10.1089/jpm.2013.0311 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA AI8HE UT WOS:000337151100013 PM 24832687 ER PT J AU Lareau, CR Sawyer, GA Wang, JH DiGiovanni, CW AF Lareau, Craig R. Sawyer, Gregory A. Wang, Joanne H. DiGiovanni, Christopher W. TI Plantar and Medial Heel Pain: Diagnosis and Management SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID SHOCK-WAVE THERAPY; TARSAL TUNNEL-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; CORTICOSTEROID INJECTION; LATERAL PLANTAR; CONTROLLED MULTICENTER; CLINICAL-TRIAL; 1ST BRANCH; FOLLOW-UP; FASCIITIS AB Heel pain is commonly encountered in orthopaedic practice. Establishing an accurate diagnosis is critical, but it can be challenging due to the complex regional anatomy. Subacute and chronic plantar and medial heel pain are most frequently the result of repetitive microtrauma or compression of neurologic structures, such as plantar fasciitis, heel pad atrophy, Baxter nerve entrapment, calcaneal stress fracture, and tarsal tunnel syndrome. Most causes of inferior heel pain can be successfully managed nonsurgically. Surgical intervention is reserved for patients who do not respond to nonsurgical measures. Although corticosteroid injections have a role in the management of select diagnoses, they should be used with caution. C1 [Lareau, Craig R.; Sawyer, Gregory A.; Wang, Joanne H.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Lareau, Craig R.; Sawyer, Gregory A.] Rhode Isl Hosp, Providence, RI USA. [DiGiovanni, Christopher W.] Harvard Univ, Sch Med, Boston, MA USA. [DiGiovanni, Christopher W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lareau, CR (reprint author), Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. FU BioMimetic Therapeutics; Wright Medical Technology FX Dr. Sawyer or an immediate family member serves as a paid consultant to Mitek. Dr. DiGiovanni or an immediate family member has received royalties from Extremity Medical; is a member of a speakers' bureau or has made paid presentations on behalf of BioMimetic Therapeutics, Extremity Medical, and Wright Medical Technology; serves as a paid consultant to BESPA, BioMimetic Therapeutics, Extremity 'Medical, and Wright Medical Technology; has stock or stock options held in Extremity Medical and Wright Medical Technology; has received research or institutional support from BioMimetic Therapeutics and Wright Medical Technology; and has received nonincome support (such as equipment or services), commercially derived honoraria, or other non-research-related funding (such as paid travel) from CuraMedix and Performance Orthotics. Neither of the following authors nor 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. Lareau and Ms. Wang. NR 68 TC 7 Z9 8 U1 4 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-151X EI 1940-5480 J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD JUN PY 2014 VL 22 IS 6 BP 372 EP 380 DI 10.5435/JAAOS-22-06-372 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AI4JE UT WOS:000336830700005 PM 24860133 ER PT J AU Anatchkova, MD Barysauskas, CM Kinney, RL Kiefe, CI Ash, AS Lombardini, L Allison, JJ AF Anatchkova, Milena D. Barysauskas, Constance M. Kinney, Rebecca L. Kiefe, Catarina I. Ash, Arlene S. Lombardini, Lisa Allison, Jeroan J. TI Psychometric Evaluation of the Care Transition Measure in TRACE-CORE: Do We Need a Better Measure? SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute coronary syndromes; care transitions measure; validity; IRT scoring ID PATIENT-REPORTED OUTCOMES; ITEM RESPONSE THEORY; QUALITY; PRECISION AB Background-The quality of transitional care is associated with important health outcomes such as rehospitalization and costs. The widely used Care Transitions Measure (CTM-15) was developed with a classic test theory approach; its short version (CTM-3) was included in the CAHPS Hospital Survey. We conducted a psychometric evaluation of both measures and explored whether item response theory (IRT) could produce a more precise measure. Methods and Results-As part of the Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education, 1545 participants were interviewed during an acute coronary syndrome hospitalization, providing information on general health status (Short Form-36), CTM-15, health utilization, and care process questions at 1 month postdischarge. We used classic and IRT analyses and compared the measurement precision of CTM-15-, CTM-3-, and CTM-IRT-based score using relative validity. Participants were 79% non-Hispanic white and 67% male, with an average age of 62 years. The CTM-15 had good internal consistency (Cronbach's alpha=0.95) but demonstrated acquiescence bias (8.7% participants responded "Strongly agree" and 19% responded "Agree" to all items) and limited score variability. These problems were more pronounced for the CTM-3. The CTM-15 differentiated between patient groups defined by self-reported health status, health care utilization, and care transition process indicators. Differences between groups were small (2 to 3 points). There was no gain in measurement precision from IRT scoring. The CTM-3 was not significantly lower for patients reporting rehospitalization or emergency department visits. Conclusion-We identified psychometric challenges of the CTM, which may limit its value in research and practice. These results are in line with emerging evidence of gaps in the validity of the measure. C1 [Anatchkova, Milena D.; Kinney, Rebecca L.; Kiefe, Catarina I.; Ash, Arlene S.; Lombardini, Lisa; Allison, Jeroan J.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01655 USA. [Barysauskas, Constance M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Anatchkova, MD (reprint author), Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, 55 Lake Ave N,ACCES7, Worcester, MA 01655 USA. EM milena.Anatchkova@umassmed.edu FU National Institutes of Health, National Heart, Lung, and Blood Institute [1U01HL105268]; National Center for Research Resources [UL1RR031982]; NIH/NCRR; University of Massachusetts Center for Clinical and Translational Sciences, Biostatistics, Epidemiology & Research Design Component (BERD); Center for Health Equity Intervention Research (CHEIR) [P60 MD006912]; PhRMA Foundation Started Grant FX TRACE-CORE is supported by the National Institutes of Health, National Heart, Lung, and Blood Institute grant 1U01HL105268. Research also supported by UL1RR031982 from the National Center for Research Resources, NIH/NCRR, University of Massachusetts Center for Clinical and Translational Sciences, Biostatistics, Epidemiology & Research Design Component (BERD), and The Center for Health Equity Intervention Research (CHEIR), grant P60 MD006912. Partial salary support is additionally provided by the PhRMA Foundation Started Grant (Dr. Anatchkova). NR 42 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e001053 DI 10.1161/JAHA.114.001053 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI4QB UT WOS:000336848800043 PM 24901109 ER PT J AU Ho, JE Larson, MG Ghorbani, A Cheng, S Coglianese, EE Vasan, RS Wang, TJ AF Ho, Jennifer E. Larson, Martin G. Ghorbani, Anahita Cheng, Susan Coglianese, Erin E. Vasan, Ramachandran S. Wang, Thomas J. TI Long-term Cardiovascular Risks Associated With an Elevated Heart Rate: The Framingham Heart Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE cardiovascular disease; epidemiology; heart failure; risk factor ID PACEMAKER IMPLANTATION; MYOCARDIAL-INFARCTION; PHYSICAL-ACTIVITY; PROGNOSTIC-FACTOR; PULSE-RATE; MORTALITY; FAILURE; DISEASE; MEN; ATHEROSCLEROSIS AB Background-Higher heart rate has been associated with an adverse prognosis, but most prior studies focused on individuals with known cardiovascular disease or examined a limited number of outcomes. We sought to examine the association of baseline heart rate with both fatal and nonfatal outcomes during 2 decades of follow-up. Methods and Results-Our study included 4058 Framingham Heart Study participants (mean age 55 years, 56% women). Cox models were performed with multivariable adjustment for clinical risk factors and physical activity. A total of 708 participants developed incident cardiovascular disease (303 heart failure, 343 coronary heart disease, and 216 stroke events), 48 received a permanent pacemaker, and 1186 died. Baseline heart rate was associated with incident cardiovascular disease (hazard ratio [HR] 1.15 per 1 SD [11 bpm] increase in heart rate, 95% CI 1.07 to 1.24, P=0.0002), particularly heart failure (HR 1.32, 95% CI 1.18 to 1.48, P<0.0001). Higher heart rate was also associated with higher all-cause (HR 1.17, 95% CI 1.11 to 1.24, P<0.0001) and cardiovascular mortality (HR 1.18, 95% CI 1.04 to 1.33, P=0.01). Spline analyses did not suggest a lower threshold beyond which the benefit of a lower heart rate abated or increased. In contrast, individuals with a higher heart rate had a lower risk of requiring permanent pacemaker placement (HR 0.55, 95% CI 0.38 to 0.79, P=0.001). Conclusions-Individuals with a higher heart rate are at elevated long-term risk for cardiovascular events, in particular, heart failure, and all-cause death. On the other hand, a higher heart rate is associated with a lower risk of future permanent pacemaker implantation. C1 [Ho, Jennifer E.; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Wang, Thomas J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Ho, Jennifer E.; Larson, Martin G.; Cheng, Susan; Vasan, Ramachandran S.; Wang, Thomas J.] Boston Univ, Sch Med, Framingham, MA USA. [Ho, Jennifer E.] Boston Univ, Cardiovasc Med Sect, Sch Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. [Ghorbani, Anahita] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Cheng, Susan] Harvard Univ, Sch Med, Dept Med, Div Cardiol,Brigham & Womens Hosp, Boston, MA USA. [Coglianese, Erin E.] Loyola Univ Hlth Syst, Chicago, IL USA. [Wang, Thomas J.] Vanderbilt Univ, Dept Med, Div Cardiovasc Med, Nashville, TN USA. RP Ho, JE (reprint author), Boston Univ, Med Ctr, 88 East Newton St,C-818, Boston, MA 02118 USA. EM jenho@bu.edu OI Ho, Jennifer/0000-0002-7987-4768; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institutes of Health [K23-HL116780]; Boston University School of Medicine Department of Medicine; Ellison Foundation FX This work was partially supported by the Framingham Heart Study of the National Heart, Lung, and Blood Institute (contract N01-HC-25195). Dr Ho is supported by National Institutes of Health grant K23-HL116780 and a Boston University School of Medicine Department of Medicine Career Investment Award. Dr Cheng is supported by an award from the Ellison Foundation. NR 37 TC 20 Z9 20 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000668 DI 10.1161/JAHA.113.000668 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI4QB UT WOS:000336848800008 PM 24811610 ER PT J AU Ovbiagele, B Schwamm, LH Smith, EE Grau-Sepulveda, MV Saver, JL Bhatt, DL Hernandez, AF Peterson, ED Fonarow, GC AF Ovbiagele, Bruce Schwamm, Lee H. Smith, Eric E. Grau-Sepulveda, Maria V. Saver, Jeffrey L. Bhatt, Deepak L. Hernandez, Adrian F. Peterson, Eric D. Fonarow, Gregg C. TI Patterns of Care Quality and Prognosis Among Hospitalized Ischemic Stroke Patients With Chronic Kidney Disease SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE chronic kidney disease; glomerular Filtration Rate; guidelines; ischemic stroke; outcomes; prognosis; quality indicators; renal ID CORONARY-ARTERY-DISEASE; OF-CARE; THROMBOLYTIC THERAPY; GUIDELINES-STROKE; RENAL DYSFUNCTION; HEART-FAILURE; OUTCOMES; ASSOCIATION; RISK; PREVENTION AB Background-Relatively little is known about the quality of care and outcomes for hospitalized ischemic stroke patients with chronic kidney disease (CKD). We examined quality of care and in-hospital prognoses among patients with CKD in the Get With The Guidelines-Stroke (GWTG-Stroke) program Methods and Results-We analyzed 679 827 patients hospitalized with ischemic stroke from 1564 US centers participating in the GWTG-Stroke program between January 2009 and December 2012. Use of 7 predefined ischemic stroke performance measures, composite "defect-free" care compliance, and in-hospital mortality were examined based on glomerular filtration rate (GFR) categorized as a dichotomous (+CKD as <60) or rank-ordered variable: normal (>= 90), mild (<= 60 to <90), moderate (>= 30 to <60), severe (>= 15 to <30), and kidney failure (<15 or dialysis). There were 236 662 (35%) ischemic stroke patients with CKD. Patients with severe renal dysfunction or failure were significantly less likely to receive guideline-based therapies. Compared with patients with normal kidney function (>= 90), those with CKD (adjusted OR 0.91 [95% CI: 0.89 to 0.92]), moderate dysfunction (adjusted OR 0.94 [95% CI: 0.92 to 0.97]), severe dysfunction (adjusted OR 0.80 [95% CI: 0.77 to 0.84]), or failure (adjusted OR 0.72 [95% CI: 0.68 to 0.0.76]), were less likely to receive 100% defect-free care measure compliance. Inpatient mortality was higher for patients with CKD (adjusted odds ratio 1.44 [95% CI: 1.40 to 1.47]), and progressively rose with more severe renal dysfunction. Conclusions-Despite higher in-hospital mortality rates, ischemic stroke patients with CKD, especially those with greater severity of renal dysfunction, were less likely to receive important guideline-recommended therapies. C1 [Ovbiagele, Bruce] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Outcomes Res & Assessment Grp, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Ovbiagele, B (reprint author), Med Univ S Carolina, Dept Neurosci, 96 Jonathan Lucas St,CSB 301,MSC 606, Charleston, SC 29425 USA. EM ovibes@musc.edu RI Hernandez, Adrian F./A-7818-2016; OI Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU American Heart Association; American Stroke Association; Pfizer (New York, NY); Merck-Schering Plough Partnership (North Wales, PA) FX The Get With The Guidelines Program (GWTG) is funded by the American Heart Association and the American Stroke Association. The program is also supported in part by unrestricted educational grants to the American Heart Association by Pfizer (New York, NY) and the Merck-Schering Plough Partnership (North Wales, PA), who did not participate in the design, analysis, or manuscript preparation, and did not require approval of this manuscript for submission. NR 23 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000905 DI 10.1161/JAHA.114.000905 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI4QB UT WOS:000336848800035 PM 24904017 ER PT J AU Sarma, A Cannon, CP de Lemos, J Rouleau, JL Lewis, EF Guo, JP Mega, JL Sabatine, MS O'Donoghue, ML AF Sarma, Amy Cannon, Christopher P. de Lemos, James Rouleau, Jean L. Lewis, Eldrin F. Guo, Jianping Mega, Jessica L. Sabatine, Marc S. O'Donoghue, Michelle L. TI The Incidence of Kidney Injury for Patients Treated With a High-Potency Versus Moderate-Potency Statin Regimen After an Acute Coronary Syndrome SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute coronary syndrome; acute kidney injury; kidney; statins ID TO-Z TRIAL; MYOCARDIAL-INFARCTION; REDUCTASE INHIBITORS; SHORT-TERM; SIMVASTATIN; ATORVASTATIN; THERAPY; EXPRESSION; CELLS; RAT AB Background-Observational studies have raised concerns that high-potency statins increase the risk of acute kidney injury. We therefore examined the incidence of kidney injury across 2 randomized trials of statin therapy. Methods and Results-PROVE IT-TIMI 22 enrolled 4162 subjects after an acute coronary syndrome (ACS) and randomized them to atorvastatin 80 mg/day versus pravastatin 40 mg/day. A-to-Z enrolled 4497 subjects after ACS and randomized them to a high-potency (simvastatin 40 mg/dayx1 months, then simvastatin 80 mg/day) versus a delayed moderate-potency statin strategy (placebox4 months, then simvastatin 20 mg/day). Serum creatinine was assessed centrally at serial time points. Adverse events (AEs) relating to kidney injury were identified through database review. Across both trials, mean serum creatinine was similar between treatment arms at baseline and throughout follow-up. In A-to-Z, the incidence of a 1.5-fold or >= 0.3 mg/dL rise in serum creatinine was 11.4% for subjects randomized to a high-potency statin regimen versus 12.4% for those on a delayed moderate-potency regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.76 to 1.10; P=0.33). In PROVE IT-TIMI 22, the incidence was 9.4% for subjects randomized to atorvastatin 80 mg/day and 10.6% for subjects randomized to pravastatin 40 mg/day (OR, 0.88; 95% CI, 0.71 to 1.09; P=0.25). Consistent results were observed for different kidney injury thresholds and in individuals with diabetes mellitus or with moderate renal dysfunction. The incidence of kidney injury-related adverse events (AEs) was not statistically different for patients on a high-potency versus moderate-potency statin regimen (OR, 1.06; 95% CI, 0.68 to 1.67; P=0.78). Conclusions-For patients enrolled in 2 large randomized trials of statin therapy after ACS, the use of a high-potency statin regimen did not increase the risk of kidney injury. C1 [Cannon, Christopher P.; Lewis, Eldrin F.; Guo, Jianping; Mega, Jessica L.; Sabatine, Marc S.; O'Donoghue, Michelle L.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Sarma, Amy] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [de Lemos, James] UT Southwestern Med Ctr, Dallas, TX USA. [Rouleau, Jean L.] Univ Montreal, Div Cardiovasc, Montreal, PQ, Canada. RP O'Donoghue, ML (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM modonoghue@partners.org FU Bristol-Myers Squibb; Sankyo; Merck FX The PROVE IT-TIMI 22 trial was supported by Bristol-Myers Squibb and Sankyo. The A-to-Z trial was supported by Merck. The current analysis received no financial support. NR 28 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000784 DI 10.1161/JAHA.114.000784 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AI4QB UT WOS:000336848800018 PM 24786143 ER PT J AU Madani, N Princiotto, AM Schon, A LaLonde, J Feng, Y Freire, E Park, J Courter, JR Jones, DM Robinson, J Liao, HX Moody, MA Permar, S Haynes, B Smith, AB Wyatt, R Sodroski, J AF Madani, Navid Princiotto, Amy M. Schoen, Arne LaLonde, Judith Feng, Yu Freire, Ernesto Park, Jongwoo Courter, Joel R. Jones, David M. Robinson, James Liao, Hua-Xin Moody, M. Anthony Permar, Sallie Haynes, Barton Smith, Amos B., III Wyatt, Richard Sodroski, Joseph TI CD4-Mimetic Small Molecules Sensitize Human Immunodeficiency Virus to Vaccine-Elicited Antibodies SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 ENVELOPE GLYCOPROTEIN; CORECEPTOR BINDING-SITE; STRUCTURE-BASED DESIGN; NEUTRALIZING ANTIBODY; TYPE-1 ENVELOPE; MONOCLONAL-ANTIBODIES; GP120 GLYCOPROTEINS; ENTRY INHIBITORS; VARIABLE REGIONS; IMMUNOGEN DESIGN AB Approaches to prevent human immunodeficiency virus (HIV-1) transmission are urgently needed. Difficulties in eliciting antibodies that bind conserved epitopes exposed on the unliganded conformation of the HIV-1 envelope glycoprotein (Env) trimer represent barriers to vaccine development. During HIV-1 entry, binding of the gp120 Env to the initial receptor, CD4, triggers conformational changes in Env that result in the formation and exposure of the highly conserved gp120 site for interaction with the coreceptors, CCR5 and CXCR4. The DMJ compounds (+)-DMJ-I-228 and (+)-DMJ-II-121 bind gp120 within the conserved Phe 43 cavity near the CD4-binding site, block CD4 binding, and inhibit HIV-1 infection. Here we show that the DMJ compounds sensitize primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies directed against CD4-induced (CD4i) epitopes and the V3 region, two gp120 elements involved in coreceptor binding. Importantly, the DMJ compounds rendered primary HIV-1 sensitive to neutralization by antisera elicited by immunization of rabbits with HIV-1 gp120 cores engineered to assume the CD4-bound state. Thus, small molecules like the DMJ compounds may be useful as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies. C1 [Madani, Navid; Princiotto, Amy M.; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Madani, Navid; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Feng, Yu; Wyatt, Richard] Scripps Res Inst, TSRI, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [LaLonde, Judith] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. [Park, Jongwoo; Courter, Joel R.; Jones, David M.; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Robinson, James] Tulane Univ Med Ctr, Dept Pediat, New Orleans, LA USA. [Liao, Hua-Xin; Moody, M. Anthony; Permar, Sallie; Haynes, Barton] Duke Univ Med Ctr, Duke Human Vaccine Inst, Dept Immunol, Dept Med, Durham, NC USA. [Sodroski, Joseph] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU National Institutes of Health [GM56550, AI100645, AI24755]; International AIDS Vaccine Initiative; National Science Foundation [MCB-1157506]; amfAR [107431-45-RFNT]; NIH [AI090682]; Ragon Institute Innovation Award FX This study was supported by the National Institutes of Health (grants GM56550, AI100645, and AI24755), the International AIDS Vaccine Initiative, and the late William F. McCarty-Cooper. E. F. thanks the National Science Foundation for support (MCB-1157506). N.M. was supported by amfAR grant 107431-45-RFNT, NIH grant AI090682, and a Ragon Institute Innovation Award. NR 91 TC 19 Z9 19 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 JUN PY 2014 VL 88 IS 12 BP 6542 EP 6555 DI 10.1128/JVI.00540-14 PG 14 WC Virology SC Virology GA AI5HF UT WOS:000336895600004 PM 24696475 ER PT J AU Kasinath, BS AF Kasinath, Balakuntalam S. TI Hydrogen sulfide to the rescue in obstructive kidney injury SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID CYSTATHIONINE-GAMMA-LYASE; RENAL ISCHEMIA/REPERFUSION; CELLS AB Hydrogen sulfide is a gasotransmitter with far-reaching effects on cell function. Studies show that, depending on the context, hydrogen sulfide can function as an ameliorative agent or as a mediator of kidney injury. C1 [Kasinath, Balakuntalam S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Kasinath, BS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, MC7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu FU NIDDK NIH HHS [R01 DK077295] NR 12 TC 6 Z9 6 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2014 VL 85 IS 6 BP 1255 EP 1258 DI 10.1038/ki.2013.529 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA AI4FG UT WOS:000336820500002 PM 24875544 ER PT J AU George, B Fan, QF Dlugos, CP Soofi, AA Zhang, JD Verma, R Park, TJ Wong, H Curran, T Nihalani, D Holzman, LB AF George, Britta Fan, Qingfeng Dlugos, Christopher P. Soofi, Abdulsalam A. Zhang, Jidong Verma, Rakesh Park, Tae-Ju Wong, Hetty Curran, Tom Nihalani, Deepak Holzman, Lawrence B. TI Crk1/2 and CrkL form a hetero-oligomer and functionally complement each other during podocyte morphogenesis SO KIDNEY INTERNATIONAL LA English DT Article DE cytoskeleton; nephrin; podocyte; signaling ID ACTIN CYTOSKELETON; SLIT DIAPHRAGM; INTERCELLULAR JUNCTION; TRANSGENIC MICE; NEPHRIN; EXPRESSION; PROTEINS; GENE; PROMOTES; FAMILY AB Activation of the slit diaphragm protein nephrin induces actin cytoskeletal remodeling, resulting in lamellipodia formation in podocytes in vitro in a phosphatidylinositol-3 kinase-, focal adhesion kinase-, Cas-, and Crk1/2-dependent fashion. In mice, podocyte-specific deletion of Crk1/2 prevents or attenuates foot process effacement in two models of podocyte injury. This suggests that cellular mechanisms governing lamellipodial protrusion in vitro are similar to those in vivo during foot process effacement. As Crk1/2-null mice developed and aged normally, we tested whether the Crk1/2 paralog, CrkL, functionally complements Crk1/2 in a podocyte-specific context. Podocyte-specific CrkL-null mice, like podocyte-specific Crk1/2-null mice, developed and aged normally but were protected from protamine sulfate-induced foot process effacement. Simultaneous podocyte-specific deletion of Crk1/2 and CrkL resulted in albuminuria detected by 6 weeks postpartum and associated with altered podocyte process architecture. Nephrin-induced lamellipodia formation in podocytes in vitro was CrkL-dependent. CrkL formed a hetero-oligomer with Crk2 and, like Crk2, was recruited to tyrosine phosphorylated nephrin. Thus, Crk1/2 and CrkL are physically linked, functionally complement each other during podocyte foot process spreading, and together are required for developing typical foot process architecture. C1 [George, Britta; Fan, Qingfeng; Zhang, Jidong; Wong, Hetty; Nihalani, Deepak; Holzman, Lawrence B.] Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. [George, Britta; Dlugos, Christopher P.] Univ Klinikum Munster, Med Klin & Poliklin D, Munster, Germany. [Soofi, Abdulsalam A.; Verma, Rakesh] Univ Michigan, Div Nephrol, Ann Arbor, MI 48109 USA. [Park, Tae-Ju; Curran, Tom] Childrens Hosp Philadelphia, Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Holzman, Lawrence B.] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Holzman, LB (reprint author), Univ Penn, Renal Electrolyte & Hypertens Div, 405 Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA. EM lholzman@upenn.edu RI Curran, Tom/D-7515-2011; OI Park, Taeju/0000-0003-3897-3994 FU NIDDK [DK080751]; Department of Veterans Affairs; Deutsche Forschungsgemeinschaft [GE 2158/1-1, GE 2158/3-1]; Pennsylvania Department of Health Cure Formulary [4100047628] FX This work was supported by grants to LBH from the NIDDK (DK080751) and the Department of Veterans Affairs, and to BG from the Deutsche Forschungsgemeinschaft (GE 2158/1-1, GE 2158/3-1). This work was also supported by a Pennsylvania Department of Health Cure Formulary grant to TC (SAP #4100047628). NR 32 TC 7 Z9 7 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2014 VL 85 IS 6 BP 1382 EP 1394 DI 10.1038/ki.2013.556 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA AI4FG UT WOS:000336820500020 PM 24499776 ER PT J AU Hunemohr, N Paganetti, H Greilich, S Jakel, O Seco, J AF Huenemohr, Nora Paganetti, Harald Greilich, Steffen Jaekel, Oliver Seco, Joao TI Tissue decomposition from dual energy CT data for MC based dose calculation in particle therapy SO MEDICAL PHYSICS LA English DT Article DE dual energy CT; stoichiometric calibration; Monte Carlo; composition; WEPL; range uncertainty ID MONTE-CARLO SIMULATIONS; EFFECTIVE ATOMIC NUMBER; COMPUTED-TOMOGRAPHY; RANGE UNCERTAINTIES; HOUNSFIELD UNITS; BRACHYTHERAPY; DISTRIBUTIONS; SINGLE; BEAMS; SEGMENTATION AB Purpose: The authors describe a novel method of predicting mass density and elemental mass fractions of tissues from dual energy CT (DECT) data for Monte Carlo (MC) based dose planning. Methods: The relative electron density rho(e) and effective atomic number Z(eff) are calculated for 71 tabulated tissue compositions. For MC simulations, the mass density is derived via one linear fit in the rho(e) that covers the entire range of tissue compositions (except lung tissue). Elemental mass fractions are predicted from the rho(e) and the Z(eff) in combination. Since particle therapy dose planning and verification is especially sensitive to accurate material assignment, differences to the ground truth are further analyzed for mass density, I-value predictions, and stopping power ratios (SPR) for ions. Dose studies with monoenergetic proton and carbon ions in 12 tissues which showed the largest differences of single energy CT (SECT) to DECT are presented with respect to range uncertainties. The standard approach (SECT) and the new DECT approach are compared to reference Bragg peak positions. Results: Mean deviations to ground truth in mass density predictions could be reduced for soft tissue from (0.5 +/- 0.6)% (SECT) to (0.2 +/- 0.2)% with the DECT method. Maximum SPR deviations could be reduced significantly for soft tissue from 3.1% (SECT) to 0.7% (DECT) and for bone tissue from 0.8% to 0.1%. Mean I-value deviations could be reduced for soft tissue from (1.1 +/- 1.4%, SECT) to (0.4 +/- 0.3%) with the presented method. Predictions of elemental composition were improved for every element. Mean and maximum deviations from ground truth of all elemental mass fractions could be reduced by at least a half with DECT compared to SECT (except soft tissue hydrogen and nitrogen where the reduction was slightly smaller). The carbon and oxygen mass fraction predictions profit especially from the DECT information. Dose studies showed that most of the 12 selected tissues would profit significantly (up to 2.2%) from DECT material decomposition with no noise present. The rho(e) associated with an absolute noise of +/- 0.01 and Z(eff) associated with an absolute noise of +/- 0.2 resulted in +/- 10% standard variation in the carbon and oxygen mass fraction prediction. Conclusions: Accurate stopping power prediction is mainly determined by the correct mass density prediction. Theoretical improvements in range predictions with DECT data in the order of 0.1%-2.1% were observed. Further work is needed to quantify the potential improvements from DECT compared to SECT in measured image data associated with artifacts and noise. (C) 2014 American Association of Physicists in Medicine. C1 [Huenemohr, Nora; Greilich, Steffen; Jaekel, Oliver] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Paganetti, Harald; Seco, Joao] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Paganetti, Harald; Seco, Joao] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Jaekel, Oliver] Univ Heidelberg Hosp, Dept Radiat Oncol & Radiat Therapy, D-69120 Heidelberg, Germany. RP Hunemohr, N (reprint author), German Canc Res Ctr, D-69120 Heidelberg, Germany. EM n.huenemohr@dkfz.de OI Greilich, Steffen/0000-0001-6237-7936 FU NCI NIH HHS [P01 CA21239, P01 CA021239] NR 34 TC 18 Z9 18 U1 1 U2 13 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 JUN PY 2014 VL 41 IS 6 AR 061714 DI 10.1118/1.4875976 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI7UR UT WOS:000337106300016 PM 24877809 ER PT J AU Schaefferkoetter, J Ouyang, JS Rakvongthai, Y Nappi, C El Fakhri, G AF Schaefferkoetter, Joshua Ouyang, Jinsong Rakvongthai, Yothin Nappi, Carmela El Fakhri, Georges TI Effect of time-of-flight and point spread function modeling on detectability of myocardial defects in PET SO MEDICAL PHYSICS LA English DT Article DE time-of-flight; point spread function; myocardial defect; detectability; channelized Hotelling observer ID POSITRON-EMISSION-TOMOGRAPHY; LESION DETECTION; HUMAN-OBSERVER; IMPACT; RECONSTRUCTION; NOISE; DEFINITION; PERFUSION; LROC AB Purpose: A study was designed to investigate the impact of time-of-flight (TOF) and point spread function (PSF) modeling on the detectability of myocardial defects. Methods: Clinical FDG-PET data were used to generate populations of defect-present and defect-absent images. Defects were incorporated at three contrast levels, and images were reconstructed by ordered subset expectation maximization (OSEM) iterative methods including ordinary Poisson, alone and with PSF, TOF, and PSF+TOF. Channelized Hotelling observer signal-to-noise ratio (SNR) was the surrogate for human observer performance. Results: For three iterations, 12 subsets, and no postreconstruction smoothing, TOF improved overall defect detection SNR by 8.6% as compared to its non-TOF counterpart for all the defect contrasts. Due to the slow convergence of PSF reconstruction, PSF yielded 4.4% less SNR than non-PSF. For reconstruction parameters (iteration number and postreconstruction smoothing kernel size) optimizing observer SNR, PSF showed larger improvement for faint defects. The combination of TOF and PSF improved mean detection SNR as compared to non-TOF and non-PSF counterparts by 3.0% and 3.2%, respectively. Conclusions: For typical reconstruction protocol used in clinical practice, i.e., less than five iterations, TOF improved defect detectability. In contrast, PSF generally yielded less detectability. For large number of iterations, TOF+PSF yields the best observer performance. (C) 2014 American Association of Physicists in Medicine. C1 [Schaefferkoetter, Joshua] A STAR NUS Clin Imaging & Res Ctr CIRC, Singapore 117599, Singapore. [Ouyang, Jinsong; Rakvongthai, Yothin; El Fakhri, Georges] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Ouyang, Jinsong; Rakvongthai, Yothin; Nappi, Carmela; El Fakhri, Georges] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Nappi, Carmela] Univ Naples Federico II, Dept Adv Biomed Sci, I-80131 Naples, Italy. [Nappi, Carmela] SDN Fdn, Inst Diagnost & Nucl Dev, I-80142 Naples, Italy. RP Schaefferkoetter, J (reprint author), A STAR NUS Clin Imaging & Res Ctr CIRC, Singapore 117599, Singapore. EM dnrjds@nus.edu.sg FU NCI NIH HHS [R01-CA165221, R01 CA165221]; NHLBI NIH HHS [R01 HL118261, R01-HL118261, R01-HL110241, R01 HL110241]; NIBIB NIH HHS [T32-EB013180, T32 EB013180] NR 34 TC 3 Z9 3 U1 1 U2 10 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 JUN PY 2014 VL 41 IS 6 AR 062502 DI 10.1118/1.4875725 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI7UR UT WOS:000337106300043 PM 24877836 ER PT J AU Yip, S Rottmann, J Berbeco, R AF Yip, Stephen Rottmann, Joerg Berbeco, Ross TI The impact of cine EPID image acquisition frame rate on markerless soft-tissue tracking SO MEDICAL PHYSICS LA English DT Article DE EPID; markerless tracking; acquisition frame rate stereotactic body radiotherapy ID STEREOTACTIC BODY RADIOTHERAPY; RADIATION-THERAPY; LUNG-CANCER; VERIFICATION; FEASIBILITY; TUMORS AB Purpose: Although reduction of the cine electronic portal imaging device (EPID) acquisition frame rate through multiple frame averaging may reduce hardware memory burden and decrease image noise, it can hinder the continuity of soft-tissue motion leading to poor autotracking results. The impact of motion blurring and image noise on the tracking performance was investigated. Methods: Phantom and patient images were acquired at a frame rate of 12.87 Hz with an amorphous silicon portal imager (AS1000, Varian Medical Systems, Palo Alto, CA). The maximum frame rate of 12.87 Hz is imposed by the EPID. Low frame rate images were obtained by continuous frame averaging. A previously validated tracking algorithm was employed for autotracking. The difference between the programmed and autotracked positions of a Las Vegas phantom moving in the superior-inferior direction defined the tracking error (delta). Motion blurring was assessed by measuring the area change of the circle with the greatest depth. Additionally, lung tumors on 1747 frames acquired at 11 field angles from four radiotherapy patients are manually and automatically tracked with varying frame averaging. d was defined by the position difference of the two tracking methods. Image noise was defined as the standard deviation of the background intensity. Motion blurring and image noise are correlated with d using Pearson correlation coefficient (R). Results: For both phantom and patient studies, the autotracking errors increased at frame rates lower than 4.29 Hz. Above 4.29 Hz, changes in errors were negligible with delta < 1.60 mm. Motion blurring and image noise were observed to increase and decrease with frame averaging, respectively. Motion blurring and tracking errors were significantly correlated for the phantom (R = 0.94) and patient studies (R = 0.72). Moderate to poor correlation was found between image noise and tracking error with R -0.58 and -0.19 for both studies, respectively. Conclusions: Cine EPID image acquisition at the frame rate of at least 4.29 Hz is recommended. Motion blurring in the images with frame rates below 4.29 Hz can significantly reduce the accuracy of autotracking. (C) 2014 American Association of Physicists in Medicine. C1 [Yip, Stephen] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yip, S (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM syip@lroc.harvard.edu FU NCI NIH HHS [R21 CA156068, R21CA156068] NR 25 TC 4 Z9 4 U1 0 U2 3 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 JUN PY 2014 VL 41 IS 6 AR 061702 DI 10.1118/1.4873322 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI7UR UT WOS:000337106300004 PM 24877797 ER PT J AU Pop, MS Stransky, N Garvie, CW Theurillat, JP Hartman, EC Lewis, TA Zhong, C Culyba, EK Lin, F Daniels, DS Pagliarini, R Ronco, L Koehler, AN Garraway, LA AF Pop, Marius S. Stransky, Nicolas Garvie, Colin W. Theurillat, Jean-Philippe Hartman, Emily C. Lewis, Timothy A. Zhong, Cheng Culyba, Elizabeth K. Lin, Fallon Daniels, Douglas S. Pagliarini, Raymond Ronco, Lucienne Koehler, Angela N. Garraway, Levi A. TI A Small Molecule That Binds and Inhibits the ETV1 Transcription Factor Oncoprotein SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID DIVERSE SMALL MOLECULES; ETS PROTEIN ER81; PROSTATE-CANCER; CELL INVASION; IN-VITRO; GENE; ACTIVATION; DISCOVERY; MELANOMA; TARGET AB Members of the ETS transcription factor family have been implicated in several cancers, where they are often dysregulated by genomic derangement. ETS variant 1 (ETV1) is an ETS factor gene that undergoes chromosomal translocation in prostate cancers and Ewing sarcomas, amplification in melanomas, and lineage dysregulation in gastrointestinal stromal tumors. Pharmacologic perturbation of ETV1 would be appealing in these cancers; however, oncogenic transcription factors are often deemed "undruggable" by conventional methods. Here, we used small-molecule microarray screens to identify and characterize drug-like compounds that modulate the biologic function of ETV1. We identified the 1,3,5-triazine small molecule BRD32048 as a top candidate ETV1 perturbagen. BRD32048 binds ETV1 directly, modulating both ETV1-mediated transcriptional activity and invasion of ETV1-driven cancer cells. Moreover, BRD32048 inhibits p300-dependent acetylation of ETV1, thereby promoting its degradation. These results point to a new avenue for pharmacologic ETV1 inhibition and may inform a general means to discover small molecule perturbagens of transcription factor oncoproteins. (C) 2014 AACR. C1 [Pop, Marius S.; Theurillat, Jean-Philippe; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pop, Marius S.; Stransky, Nicolas; Garvie, Colin W.; Theurillat, Jean-Philippe; Hartman, Emily C.; Lewis, Timothy A.; Zhong, Cheng; Culyba, Elizabeth K.; Daniels, Douglas S.; Ronco, Lucienne; Koehler, Angela N.; Garraway, Levi A.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Lin, Fallon; Pagliarini, Raymond] MIT, Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Koehler, Angela N.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Koehler, Angela N.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Garraway, LA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1542, Boston, MA 02115 USA. EM levi_garraway@dfci.harvard.edu OI Daniels, Douglas/0000-0003-0238-9403 FU National Cancer Institute's Initiative for Chemical Genetics (ICG) [N01-CO-12400]; Cancer Target Discovery and Development (CTD2) Network [RC2 CA148399]; New Innovator Award from the National Institutes of Health; Challenge Award from the Prostate Cancer Foundation FX The project was funded by the National Cancer Institute's Initiative for Chemical Genetics (ICG) under Contract No. N01-CO-12400, and the Cancer Target Discovery and Development (CTD2) Network, under RC2 CA148399 (A.N. Koehler), a New Innovator Award from the National Institutes of Health, and a Challenge Award from the Prostate Cancer Foundation (L.A. Garraway). NR 50 TC 12 Z9 12 U1 0 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUN PY 2014 VL 13 IS 6 BP 1492 EP 1502 DI 10.1158/1535-7163.MCT-13-0689 PG 11 WC Oncology SC Oncology GA AI8LX UT WOS:000337168600010 PM 24737027 ER PT J AU Lerner-Ellis, JP Aldubayan, SH Hernandez, AL Kelly, MA Stuenkel, AJ Walsh, J Joshi, VA AF Lerner-Ellis, Jordan P. Aldubayan, Saud H. Hernandez, Amy Lovelette Kelly, Melissa Allard Stuenkel, Aaron J. Walsh, Jennifer Joshi, Victoria A. TI The spectrum of FBN1, TGF beta R1, TGF beta R2 and ACTA2 variants in 594 individuals with suspected Marfan Syndrome, Loeys-Dietz Syndrome or Thoracic Aortic Aneurysms and Dissections (TAAD) SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Marfan Syndrome; Loeys-Dietz Syndrome; Thoracic Aortic Aneurysms and Dissections; FBN1; Aortic aneurysms ID TGFBR2 MUTATIONS; FIBRILLIN-1 GENE; FEATURES; UPDATE; GHENT AB Introduction: In this study, patients suspected of having a clinical diagnosis of Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS) and Thoracic Aortic Aneurysms and Dissections (TAAD) were referred for genetic testing and examined for mutations in the FBN1, TGF beta R1, TGF beta R2 and ACTA2 genes. Methods: We examined 594 samples from unrelated individuals and different combinations of genes were sequenced, including one or more of the following: FBN1, TGF beta R1, TGF beta R2, ACTA2, and, in some cases, FBN1 was analyzed by MLPA to detect large deletions. Results: A total of 112 patients had a positive result Of those, 61 had a clinical diagnosis of MFS, eight had LDS, three had TAAD and 40 patients had clinical features with no specific diagnosis provided. A total of 44 patients had an inconclusive result; of these, 12 patients were referred with a clinical diagnosis of MFS, 4 with LDS and 9 with TAAD and 19 had no clinical diagnosis. A total of 89 mutations were novel. Conclusion: This study reveals the rate of detection of variants in several genes associated with MFS, LDS and TAAD. The evaluation of patients by individuals with expertise in the field may decrease the likelihood of ordering unnecessary molecular testing. Nevertheless, genetic testing supports the diagnosis of MFS, LDS and TAAD. (C) 2014 Elsevier Inc. All rights reserved. C1 [Lerner-Ellis, Jordan P.] Univ Toronto, Lab Med & Pathobiol, Toronto, ON, Canada. [Lerner-Ellis, Jordan P.] Univ Toronto, Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. [Lerner-Ellis, Jordan P.] Ontario Inst Canc Res, Toronto, ON, Canada. [Lerner-Ellis, Jordan P.; Hernandez, Amy Lovelette; Kelly, Melissa Allard; Joshi, Victoria A.] Partners Healthcare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA USA. [Aldubayan, Saud H.] Univ Toronto, Dept Med, Toronto, ON M5G 2C4, Canada. [Stuenkel, Aaron J.; Walsh, Jennifer] Boston Univ, Boston, MA 02215 USA. [Joshi, Victoria A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Joshi, Victoria A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Aldubayan, SH (reprint author), Univ Toronto, Dept Med, 190 Elizabeth St,R Fraser Elliott Bldg 3-805, Toronto, ON M5G 2C4, Canada. EM sdubayan@gmail.com RI Lerner-Ellis, Jordan/J-5559-2016 NR 37 TC 10 Z9 10 U1 3 U2 12 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 JUN PY 2014 VL 112 IS 2 BP 171 EP 176 DI 10.1016/j.ymgme.2014.03.011 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA AI7KF UT WOS:000337067900010 PM 24793577 ER PT J AU Zhang, B Jia, WH Matsuda, K Kweon, SS Matsuo, K Xiang, YB Shin, AS Jee, SH Kim, DH Cai, QY Long, JR Shi, JJ Wen, WQ Yang, G Zhang, YF Li, C Li, BS Guo, Y Ren, ZF Ji, BT Pan, ZZ Takahashi, A Shin, MH Matsuda, F Gao, YT Oh, JH Kim, S Ahn, YO Chan, AT Chang-Claude, J Slattery, ML Gruber, SB Schumacher, FR Stenzel, SL Casey, G Kim, HR Jeong, JY Park, JW Li, HL Hosono, S Cho, SH Kubo, M Shu, XO Zeng, YX Zheng, W AF Zhang, Ben Jia, Wei-Hua Matsuda, Koichi Kweon, Sun-Seog Matsuo, Keitaro Xiang, Yong-Bing Shin, Aesun Jee, Sun Ha Kim, Dong-Hyun Cai, Qiuyin Long, Jirong Shi, Jiajun Wen, Wanqing Yang, Gong Zhang, Yanfeng Li, Chun Li, Bingshan Guo, Yan Ren, Zefang Ji, Bu-Tian Pan, Zhi-Zhong Takahashi, Atsushi Shin, Min-Ho Matsuda, Fumihiko Gao, Yu-Tang Oh, Jae Hwan Kim, Soriul Ahn, Yoon-Ok Chan, Andrew T. Chang-Claude, Jenny Slattery, Martha L. Gruber, Stephen B. Schumacher, Fredrick R. Stenzel, Stephanie L. Casey, Graham Kim, Hyeong-Rok Jeong, Jin-Young Park, Ji Won Li, Hong-Lan Hosono, Satoyo Cho, Sang-Hee Kubo, Michiaki Shu, Xiao-Ou Zeng, Yi-Xin Zheng, Wei CA Genetics Epidemiology Colorectal C Colorectal Transdisciplinary COREC Colon Canc Family Registry TI Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; LYMPHOTOXIN-BETA-RECEPTOR; SUSCEPTIBILITY LOCI; BREAST-CANCER; COLON-CANCER; CELL-GROWTH; EXPRESSION; MUTATIONS; VARIANTS; METAANALYSIS AB Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 x 10(-8) to 9.22 x 10(-21)) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways. C1 [Zhang, Ben; Cai, Qiuyin; Long, Jirong; Shi, Jiajun; Wen, Wanqing; Yang, Gong; Zhang, Yanfeng; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA. [Jia, Wei-Hua; Pan, Zhi-Zhong; Zeng, Yi-Xin] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China. [Matsuda, Koichi] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan. [Kweon, Sun-Seog; Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Kwangju, South Korea. [Kweon, Sun-Seog] Chonnam Natl Univ, Hwasun Hosp, Jeonnam Reg Canc Ctr, Hwasun, South Korea. [Matsuo, Keitaro; Hosono, Satoyo] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 812, Japan. [Xiang, Yong-Bing; Gao, Yu-Tang; Li, Hong-Lan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Shin, Aesun] Natl Canc Ctr, Mol Epidemiol Branch, Goyang Si, South Korea. [Shin, Aesun; Ahn, Yoon-Ok] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea. [Jee, Sun Ha; Kim, Soriul] Yonsei Univ, Grad Sch Publ Hlth, Inst Hlth Promot, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea. [Kim, Dong-Hyun; Jeong, Jin-Young] Hallym Univ, Coll Med, Dept Social & Prevent Med, Okcheon Dong, South Korea. [Li, Chun] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. [Li, Bingshan] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. [Guo, Yan] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA. [Ren, Zefang] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou 510275, Guangdong, Peoples R China. [Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Takahashi, Atsushi; Kubo, Michiaki] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan. [Matsuda, Fumihiko] Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan. [Oh, Jae Hwan; Park, Ji Won] Natl Canc Ctr, Ctr Colorectal Canc, Goyang Si, South Korea. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany. [Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. [Gruber, Stephen B.; Schumacher, Fredrick R.; Stenzel, Stephanie L.; Casey, Graham] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Kim, Hyeong-Rok] Chonnam Natl Univ, Sch Med, Dept Surg, Kwangju, South Korea. [Park, Ji Won] Seoul Natl Univ Hosp, Dept Surg, Seoul 110744, South Korea. [Cho, Sang-Hee] Chonnam Natl Univ, Sch Med, Dept Hematooncol, Kwangju, South Korea. RP Zheng, W (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr,Dept Med,Div Epidemiol, Nashville, TN 37212 USA. EM wei.zheng@vanderbilt.edu RI Gallinger, Steven/E-4575-2013; Shin, Aesun/E-9145-2014; Hoffmeister, Michael/B-5745-2012; KURY, Sebastien/G-5971-2015; Kubo, Michiaki/N-7947-2015; zhang, yanfeng/E-6971-2016; Brenner, Hermann/B-4627-2017; OI Shin, Aesun/0000-0002-6426-1969; Hoffmeister, Michael/0000-0002-8307-3197; KURY, Sebastien/0000-0001-5497-0465; zhang, yanfeng/0000-0002-3859-3839; Brenner, Hermann/0000-0002-6129-1572; Bezieau, stephane/0000-0003-0095-1319; Matsuda, Koichi/0000-0001-7292-2686; Matsuo, Keitaro/0000-0003-1761-6314 FU US National Institutes of Health (NIH) [R37CA070867, R01CA082729, R01CA124558, R01CA148667, R01CA122364]; Vanderbilt University School of Medicine. Studies; Asia Colorectal Cancer Consortium include the Shanghai Women's Health Study (US NIH) [R37CA070867]; Shanghai Men's Health Study (US NIH) [R01CA082729]; Shanghai Breast and Endometrial Cancer Studies (US NIH) [R01CA064277, R01CA092585]; Shanghai Colorectal Cancer Study 3 (US NIH) [R37CA070867]; Guangzhou Colorectal Cancer Study (National Key Scientific and Technological Project) [2011ZX09307-001-04]; National Basic Research Program [2011CB504303]; Natural Science Foundation of China [81072383]; Japan BioBank Colorectal Cancer Study (grant from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government); Hwasun Cancer Epidemiology Study Colon and Rectum Cancer (HCES-CRC); Korea Center for Disease Control and Prevention; Aichi Colorectal Cancer Study [17015018, 221S0001]; Korea-NCC (National Cancer Center) Colorectal Cancer Study (Basic Science Research Program through-the National Research Foundation of Korea [2010-0010276]; National Cancer Center Korea [0910220]; Korea-Seoul Colorectal Cancer Study; KCPS-II Colorectal Cancer Study (National R&D Program for Cancer Control) [1220180]; Seoul RD Program [10526]; GECCO; CORECT; CCFR; NIH [R01CA048998]; DACHS (German Federal Ministry of Education and Research) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1, 01KH0404, 01ER0814]; HPFS (US NIH) [P01CA055075, UM1CA167552, R01137178, P50CA127003]; NHS (US NIH) [R01137178, P50CA127003, P01CA087969]; OFCCR (US NIH) [U01CA074783]; PMH (US NIH) [R01CA076366]; PHS (US NIH) [R01CA042182] FX The authors are solely responsible for the scientific content of this paper. The sponsors of this study had no role in study design, data collection, analysis or interpretation, writing of the report or the decision for submission. We thank all study participants and research staff of all parent studies for their contributions and commitment to this project, R. Courtney for DNA preparation, J. He for data processing and analyses, X. Gun for suggestions on bioinformatics analysis, and M.J. Daly and B.J. Rammer for editing and preparing the manuscript. The work at the Vanderbilt University School of Medicine was supported by US National Institutes of Health (NIH) grants R37CA070867, R01CA082729, R01CA124558, R01CA148667 and R01CA122364, as well as by Ingram Professorship and Research Reward funds from the Vanderbilt University School of Medicine. Studies (grant support) participating in the Asia Colorectal Cancer Consortium include the Shanghai Women's Health Study (US NIH, R37CA070867), the Shanghai Men's Health Study (US NIH, R01CA082729), the Shanghai Breast and Endometrial Cancer Studies (US NIH, R01CA064277 and R01CA092585; contributing only controls), Shanghai Colorectal Cancer Study 3 (US NIH, R37CA070867 and Ingram Professorship funds), the Guangzhou Colorectal Cancer Study (National Key Scientific and Technological Project, 2011ZX09307-001-04; the National Basic Research Program, 2011CB504303, contributing only controls; the Natural Science Foundation of China, 81072383, contributing only controls), the Japan BioBank Colorectal Cancer Study (grant from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government), the Hwasun Cancer Epidemiology Study Colon and Rectum Cancer (HCES-CRC; grants from the Korea Center for Disease Control and Prevention and the Jeonnam Regional Cancer Center), the Aichi Colorectal Cancer Study (Grant-in-Aid for Cancer Research, grant for the Third Term Comprehensive Control Research for Cancer and Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, 17015018 and 221S0001), the Korea-NCC (National Cancer Center) Colorectal Cancer Study (Basic Science Research Program through-the National Research Foundation of Korea, 2010-0010276; National Cancer Center Korea, 0910220), the Korea-Seoul Colorectal Cancer Study (none reported) and the KCPS-II Colorectal Cancer Study (National R&D Program for Cancer Control, 1220180; Seoul R&D Program, 10526).; We also thank B. Buecher of ASTERISK; U. Handte-Daub, M. Celik, R. Hettler-Jensen, U. Benscheid and U. Eilber of DACHS; and P. Soule, H. Ranu, I. Devivo, D.J. Hunter, Q. Guo, L. Zhu and H. Zhang of HPFS, NHS and PHS, as well as the following state cancer registries for their help: Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Nebraska, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, Tennessee, Texas, Virginia, Washington and Wyoming. We thank C. Berg and P. Prorok of PLCO; T. Riley of Information Management Services, Inc.; B. O'Brien of Westat, Inc.; B. Kopp and W Shao of SAIC-Frederick; the WHI investigators (see https://www.whi.org/researchers/SitePages/Write%20a%20Paper. aspx) and the GECCO Coordinating Center. Participating studies (grant support) in the GECCO, CORECT and CCFR GWAS meta-analysis are GECCO (US NIH, U01CA137088 and R01CA059045), DALS (US NIH, R01CA048998), DACHS (German Federal Ministry of Education and Research, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1,01KH0404 and 01ER0814), HPFS (US NIH, P01CA055075, UM1CA167552, R01137178 and P50CA127003), NHS (US NIH, R01137178, P50CA127003 and P01CA087969), OFCCR (US NIH, U01CA074783), PMH (US NIH, R01CA076366), PHS (US NIH, R01CA042182), VITAL (US NIH, K05CA154337), WHI (US NIH, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C and 268200764316C) and PLCO (US NIH, Z01CP 010200, U0IHG004446 and U01HG 004438). CORECT is supported by the National Cancer Institute as part of the GAME-ON consortium (US NIH, U19CA148107) with additional support from National Cancer Institute grants (R01CA81488 and P30CA014089), the National Human Genome Research Institute at the US NIH (T32HG000040) and the National Institute of Environmental Health Sciences at the US NIH (T32ES013678). CCFR is supported by the National Cancer Institute, US NIH under RFA CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and principal investigators of the Australasian Colorectal Cancer Family Registry (US NIH, U01CA097735), the Familial Colorectal Neoplasia Collaborative Group (US NIH, U01CA074799) (University of Southern California), the Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (US NIH, U01CA074800), the Ontario Registry for Studies of Familial Colorectal Cancer (US NIH, U01CA074783), the Seattle Colorectal Cancer Family Registry (US NIH, U01CA074794) and the University of Hawaii Colorectal Cancer Family Registry (US NIH, U01CA074806). The GWAS work was supported by a National Cancer Institute grant (US NIH, U01CA122839). OFCCR was supported by a GL2 grant from the Ontario Research Fund, Canadian Institutes of Health Research and a Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute. T.J. Hudson and B.W. Zanke are recipients of Senior Investigator Awards from the Ontario Institute for Cancer Research, through support from the Ontario Ministry of Economic Development and Innovation. ASTERISK was funded by a Regional Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC).; PLCO data sets were accessed with approval through dbGaP (CGEMS prostate cancer scan, phs000207.v1.p1; CGEMS pancreatic cancer scan, phs000206.v4.p3; and GWAS of Lung Cancer and Smoking, phs000093.v2.p2, which was funded by Z01CP 010200, U01HG004446 and U01HG 004438 from the US NIH). NR 63 TC 63 Z9 68 U1 2 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JUN PY 2014 VL 46 IS 6 BP 533 EP 542 DI 10.1038/ng.2985 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA AI4XU UT WOS:000336870700008 PM 24836286 ER PT J AU Gong, YX Zack, TI Morris, LGT Lin, K Hukkelhoven, E Raheja, R Tan, IL Turcan, S Veeriah, S Meng, S Viale, A Schumacher, SE Palmedo, P Beroukhim, R Chan, TA AF Gong, Yongxing Zack, Travis Ian Morris, Luc G. T. Lin, Kan Hukkelhoven, Ellen Raheja, Radhika Tan, I-Li Turcan, Sevin Veeriah, Selvaraju Meng, Shasha Viale, Agnes Schumacher, Steven E. Palmedo, Perry Beroukhim, Rameen Chan, Timothy A. TI Pan-cancer genetic analysis identifies PARK2 as a master regulator of G1/S cyclins SO NATURE GENETICS LA English DT Article ID COPY-NUMBER ALTERATION; F-BOX PROTEINS; CELL-CYCLE; UBIQUITIN LIGASES; MITOCHONDRIAL DEPOLARIZATION; COLORECTAL-CANCER; TUMOR-SUPPRESSOR; BREAST-CANCER; DEGRADATION; D1 AB Coordinate control of different classes of cyclins is fundamentally important for cell cycle regulation and tumor suppression, yet the underlying mechanisms are incompletely understood. Here we show that the PARK2 tumor suppressor mediates this coordination. The PARK2 E3 ubiquitin ligase coordinately controls the stability of both cyclin D and cyclin E. Analysis of approximately 5,000 tumor genomes shows that PARK2 is a very frequently deleted gene in human cancer and uncovers a striking pattern of mutual exclusivity between PARK2 deletion and amplification of CCND1, CCNE1 or CDK4-implicating these genes in a common pathway. Inactivation of PARK2 results in the accumulation of cyclin D and acceleration of cell cycle progression. Furthermore, PARK2 is a component of a new class of cullin-RING-containing ubiquitin ligases targeting both cyclin D and cyclin E for degradation. Thus, PARK2 regulates cyclin-CDK complexes, as does the CDK inhibitor p16, but acts as a master regulator of the stability of G1/S cyclins. C1 [Gong, Yongxing; Turcan, Sevin; Veeriah, Selvaraju; Meng, Shasha; Chan, Timothy A.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Zack, Travis Ian; Schumacher, Steven E.; Palmedo, Perry; Beroukhim, Rameen] Broad Inst, Cambridge, MA USA. [Zack, Travis Ian; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Zack, Travis Ian; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zack, Travis Ian; Beroukhim, Rameen] Dana Farber Canc Inst, Ctr Canc Genome Characterizat, Boston, MA 02115 USA. [Zack, Travis Ian] Harvard Univ, Biophys Program, Boston, MA 02115 USA. [Morris, Luc G. T.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. [Lin, Kan; Tan, I-Li] Weill Cornell Coll Med, New York, NY USA. [Hukkelhoven, Ellen; Raheja, Radhika] Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. [Viale, Agnes] Mem Sloan Kettering Canc Ctr, Genom Core, New York, NY 10021 USA. [Palmedo, Perry] Harvard Univ, Ctr Biomed Informat, Boston, MA 02115 USA. [Chan, Timothy A.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Chan, Timothy A.] Mem Sloan Kettering Canc Ctr, Brain Tumor Ctr, New York, NY 10021 USA. RP Chan, TA (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA. EM chant@mskcc.org OI Turcan, Sevin/0000-0002-0885-5607; Gong, Yongxing/0000-0003-1071-0375 FU US National Institutes of Health T32 grant [5T32CA160001]; US National Institutes of Health [RO1 NS086875-01]; Memorial Sloan-Kettering Cancer Center Brain Tumor Center; Sontag Foundation; Frederick Adler Fund FX We thank E. Holland, A.C. Koff and J. Huse for helpful advice. S.T. was a recipient of a US National Institutes of Health T32 grant (5T32CA160001). This work was supported by the US National Institutes of Health (RO1 NS086875-01) (T.A.C.), the Memorial Sloan-Kettering Cancer Center Brain Tumor Center (T.A.C.), the Sontag Foundation (T.A.C.) and the Frederick Adler Fund (T.A.C.). NR 53 TC 40 Z9 40 U1 0 U2 10 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 JUN PY 2014 VL 46 IS 6 BP 588 EP 594 DI 10.1038/ng.2981 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AI4XU UT WOS:000336870700015 PM 24793136 ER PT J AU Wang, YX Marino-Enriquez, A Bennett, RR Zhu, MJ Shen, YP Eilers, G Lee, JC Henze, J Fletcher, BS Gu, ZZ Fox, EA Antonescu, CR Fletcher, CDM Guo, XQ Raut, CP Demetri, GD van de Rijn, M Ordog, T Kunkel, LM Fletcher, JA AF Wang, Yuexiang Marino-Enriquez, Adrian Bennett, Richard R. Zhu, Meijun Shen, Yiping Eilers, Grant Lee, Jen-Chieh Henze, Joern Fletcher, Benjamin S. Gu, Zhizhan Fox, Edward A. Antonescu, Cristina R. Fletcher, Christopher D. M. Guo, Xiangqian Raut, Chandrajit P. Demetri, George D. van de Rijn, Matt Ordog, Tamas Kunkel, Louis M. Fletcher, Jonathan A. TI Dystrophin is a tumor suppressor in human cancers with myogenic programs SO NATURE GENETICS LA English DT Article ID GASTROINTESTINAL STROMAL TUMORS; DUCHENNE MUSCULAR-DYSTROPHY; GENE-THERAPY; RHABDOMYOSARCOMA; MUTATIONS; PROTEIN; LEIOMYOSARCOMA; CHILDHOOD; PRODUCT; TARGETS AB Many common human mesenchymal tumors, including gastrointestinal stromal tumor (GIST), rhabdomyosarcoma (RMS) and leiomyosarcoma (LMS), feature myogenic differentiation(1-3). Here we report that intragenic deletion of the dystrophin-encoding and muscular dystrophy-associated DMD gene is a frequent mechanism by which myogenic tumors progress to high-grade, lethal sarcomas. Dystrophin is expressed in the non-neoplastic and benign counterparts of GIST, RMS and LMS tumors, and DMD deletions inactivate larger dystrophin isoforms, including 427-kDa dystrophin, while preserving the expression of an essential 71-kDa isoform. Dystrophin inhibits myogenic sarcoma cell migration, invasion, anchorage independence and invadopodia formation, and dystrophin inactivation was found in 96%, 100% and 62% of metastatic GIST, embryonal RMS and LMS samples, respectively. These findings validate dystrophin as a tumor suppressor and likely anti-metastatic factor, suggesting that therapies in development for muscular dystrophies may also have relevance in the treatment of cancer. C1 [Wang, Yuexiang; Marino-Enriquez, Adrian; Zhu, Meijun; Eilers, Grant; Lee, Jen-Chieh; Henze, Joern; Fletcher, Benjamin S.; Fletcher, Christopher D. M.; Fletcher, Jonathan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Wang, Yuexiang; Marino-Enriquez, Adrian; Zhu, Meijun; Eilers, Grant; Lee, Jen-Chieh; Henze, Joern; Fletcher, Benjamin S.; Gu, Zhizhan; Fletcher, Christopher D. M.; Raut, Chandrajit P.; Fletcher, Jonathan A.] Harvard Univ, Sch Med, Boston, MA USA. [Bennett, Richard R.; Kunkel, Louis M.] Childrens Hosp, Manton Ctr Orphan Dis Res, Div Genet & Genom, Boston, MA 02115 USA. [Shen, Yiping] Childrens Hosp, Dept Lab Med, Genet Diagnost Lab, Boston, MA 02115 USA. [Shen, Yiping] Jiaotong Univ, Shanghai Childrens Med Ctr, Dept Lab Med, Shanghai, Peoples R China. [Lee, Jen-Chieh] Natl Taiwan Univ Hosp, Dept Pathol, Taipei 100, Taiwan. [Gu, Zhizhan] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Fox, Edward A.] Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA 02115 USA. [Antonescu, Cristina R.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. [Guo, Xiangqian; van de Rijn, Matt] Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA. [Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Demetri, George D.] Harvard Univ, Sch Med, Ludwig Ctr Harvard, Boston, MA USA. [Demetri, George D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ordog, Tamas] Mayo Clin, Ctr Individualized Med, Rochester, MN USA. [Ordog, Tamas] Mayo Clin, Enter Neurosci Program, Rochester, MN USA. [Ordog, Tamas] Mayo Clin, Dept Physiol & Biomed Engn, Rochester, MN USA. RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jfletcher@partners.org OI Lee, Jen-Chieh/0000-0001-7739-5934 FU US National Institutes of Health [1P50CA127003-07, 1P50CA168512-01, 5R01DK058185-12]; Virginia and Daniel K. Ludwig Trust; GIST Cancer Research Fund; Life Raft Group; Cesarini Pan-Mass Challenge for GIST; Paul's Posse of the Pan-Mass Challenge; Bernard F. and Alva B. Gimbel Foundation; Sarcoma Alliance for Research Through Collaboration; Erica Kaitz LMS Research NOW Fund FX We thank J. Tremblay (Quebec University Hospital) for the pCR3.1-miniDMD construct; T. Taguchi (Kochi Medical School) for the GIST-T1 cell line; Y. Hayashi, M. Bardsley and H. Qiu for their expert technical assistance; and S. Bauer (West German Cancer Center) for useful discussions and for funding support of J.H. This work was supported by grants from the US National Institutes of Health, including 1P50CA127003-07 (J.A.F. and G.D.D.), 1P50CA168512-01 (J.A.F., G.D.D. and A.M.-E.) and 5R01DK058185-12 (TO.), and by the Virginia and Daniel K. Ludwig Trust for Cancer Research (J.A.F. and G.D.D.), the GIST Cancer Research Fund (J.A.F.), the Life Raft Group (J.A.F., TO. and M.v.d.R.), the Cesarini Pan-Mass Challenge for GIST (J.A.F. and G.D.D.), Paul's Posse of the Pan-Mass Challenge (JAR and G.D.D.), the Bernard F. and Alva B. Gimbel Foundation (L.M.K.), the Sarcoma Alliance for Research Through Collaboration (A.M.-E.) and the Erica Kaitz LMS Research NOW Fund (J.A.F., A.M.-E. and G.D.D.). NR 40 TC 27 Z9 27 U1 0 U2 14 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 JUN PY 2014 VL 46 IS 6 BP 601 EP 606 DI 10.1038/ng.2974 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AI4XU UT WOS:000336870700017 PM 24793134 ER PT J AU Lane, AA Chapuy, B Lin, CY Tivey, T Li, HB Townsend, EC van Bodegom, D Day, TA Wu, SC Liu, HY Yoda, A Alexe, G Schinzel, AC Sullivan, TJ Malinge, S Taylor, JE Stegmaier, K Jaffe, JD Bustin, M te Kronnie, G Izraeli, S Harris, MH Stevenson, KE Neuberg, D Silverman, LB Sallan, SE Bradner, JE Hahn, WC Crispino, JD Pellman, D Weinstock, DM AF Lane, Andrew A. Chapuy, Bjoern Lin, Charles Y. Tivey, Trevor Li, Hubo Townsend, Elizabeth C. van Bodegom, Diederik Day, Tovah A. Wu, Shuo-Chieh Liu, Huiyun Yoda, Akinori Alexe, Gabriela Schinzel, Anna C. Sullivan, Timothy J. Malinge, Sebastien Taylor, Jordan E. Stegmaier, Kimberly Jaffe, Jacob D. Bustin, Michael te Kronnie, Geertruy Izraeli, Shai Harris, Marian H. Stevenson, Kristen E. Neuberg, Donna Silverman, Lewis B. Sallan, Stephen E. Bradner, James E. Hahn, William C. Crispino, John D. Pellman, David Weinstock, David M. TI Triplication of a 21q22 region contributes to B cell transformation through HMGN1 overexpression and loss of histone H3 Lys27 trimethylation SO NATURE GENETICS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EMBRYONIC STEM-CELLS; DOWN-SYNDROME; EXPRESSION; CHROMATIN; CRLF2; GENE; TRISOMY-21; MUTATIONS; PROTEINS AB Down syndrome confers a 20-fold increased risk of B cell acute lymphoblastic leukemia (B-ALL)1, and polysomy 21 is most frequent somatic aneuploidy among all B-ALLs(2). Yet the mechanistic links between chromosome 21 triplication and B-ALL remain undefined. Here we show that germline triplication of only 31 genes orthologous to human chromosome 21q22 confers mouse progenitor B cell self renewal in vitro, maturation defects in vivo and B-ALL with either the BCR-ABL fusion protein or CRLF2 with activated JAK2. Chromosome 21q22 triplication suppresses histone H3 Lys27 trimethylation (H3K27me3) in progenitor B cells and B-ALLs, and 'bivalent' genes with both H3K27me3 and H3K4me3 at their promoters in wild-type progenitor B cells are preferentially overexpressed in triplicated cells. Human B-ALLs with polysomy 21 are distinguished by their overexpression of genes marked with H3K27me3 in multiple cell types. Overexpression of HMGN1, a nucleosome remodeling protein encoded on chromosome 21q22 (refs. 3-5), suppresses H3K27me3 and promotes both B cell proliferation in vitro and B-ALL in vivo. C1 [Lane, Andrew A.; Chapuy, Bjoern; Lin, Charles Y.; Tivey, Trevor; Townsend, Elizabeth C.; van Bodegom, Diederik; Day, Tovah A.; Wu, Shuo-Chieh; Liu, Huiyun; Yoda, Akinori; Schinzel, Anna C.; Bradner, James E.; Hahn, William C.; Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Li, Hubo; Alexe, Gabriela; Silverman, Lewis B.; Sallan, Stephen E.; Pellman, David] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Schinzel, Anna C.; Taylor, Jordan E.; Stegmaier, Kimberly; Jaffe, Jacob D.; Hahn, William C.; Weinstock, David M.] Broad Inst, Cambridge, MA USA. [Sullivan, Timothy J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Microarray Core, Boston, MA 02115 USA. [Malinge, Sebastien] Inst Gustave Roussy, INSERM, U985, F-94805 Villejuif, France. [Bustin, Michael] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [te Kronnie, Geertruy] Univ Padua, Dept Pediat, Padua, Italy. [Izraeli, Shai] Chaim Sheba Med Ctr, Dept Pediat Hematooncol, Ramat Gan, Israel. [Izraeli, Shai] Tel Aviv Univ, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. [Harris, Marian H.] Childrens Hosp Boston, Dept Pathol, Boston, MA USA. [Stevenson, Kristen E.; Neuberg, Donna] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Crispino, John D.] Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA. [Pellman, David] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Lane, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM andrew_lane@dfci.harvard.edu; dweinstock@partners.org RI Bustin, Michael/G-6155-2015 OI Crispino, John/0000-0002-8182-8306; FU Conquer Cancer Foundation; Lauri Strauss Leukemia Foundation; Leukemia and Lymphoma Society; Alex Lemonade Stand Foundation; US Department of Defense; Israel Science Foundation; US Israel Binational Foundation; Stellato Fund; US National Institutes of Health/National Cancer Institute [CA15198-01, CA172387-A01] FX We thank N. Kopp and A. Schlauch for technical assistance, M. Busslinger (Research Institute of Molecular Pathology, Vienna) for the Pax5+/- mice and M. Oshimura (Tottori University) for A9 cells carrying human chromosome 21. This research was supported by the Conquer Cancer Foundation (.A.A.L.), the Lauri Strauss Leukemia Foundation (A.A.L.), the Leukemia and Lymphoma Society (A.A.L.), the Alex Lemonade Stand Foundation (A.A.L., H. Li and D.P.), the US Department of Defense (C.Y.L.), the Israel Science Foundation (S.I.), the US Israel Binational Foundation (J.D.C. and S.I.), the Stellato Fund (D.M.W.), US National Institutes of Health/National Cancer Institute R01 awards CA15198-01 and CA172387-A01 (D.M.W.) and a Translational Research Award from the Leukemia and Lymphoma Society (J.D.C. and D.M.W.). NR 31 TC 27 Z9 27 U1 2 U2 10 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 JUN PY 2014 VL 46 IS 6 BP 618 EP 623 DI 10.1038/ng.2949 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA AI4XU UT WOS:000336870700020 PM 24747640 ER PT J AU Cottini, F Hideshima, T Xu, CX Sattler, M Dori, M Agnelli, L ten Hacken, E Bertilaccio, MT Antonini, E Neri, A Ponzoni, M Marcatti, M Richardson, PG Carrasco, R Kimmelman, AC Wong, KK Caigaris-Cappio, F Blandino, G Kuehl, WM Anderson, KC Tonon, G AF Cottini, Francesca Hideshima, Teru Xu, Chunxiao Sattler, Martin Dori, Martina Agnelli, Luca ten Hacken, Elisa Bertilaccio, Maria Teresa Antonini, Elena Neri, Antonino Ponzoni, Maurilio Marcatti, Magda Richardson, Paul G. Carrasco, Ruben Kimmelman, Alec C. Wong, Kwok-Kin Caigaris-Cappio, Federico Blandino, Giovanni Kuehl, W. Michael Anderson, Kenneth C. Tonon, Giovanni TI Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers SO NATURE MEDICINE LA English DT Article ID YES-ASSOCIATED PROTEIN; ABL TYROSINE KINASE; C-ABL; MULTIPLE-MYELOMA; TUMOR-SUPPRESSOR; P73; PATHWAY; PHOSPHORYLATION; TUMORIGENESIS; ACTIVATION AB Oncogene-induced DNA damage elicits genomic instability in epithelial cancer cells, but apoptosis is blocked through inactivation of the tumor suppressor p53. In hematological cancers, the relevance of ongoing DNA damage and the mechanisms by which apoptosis is suppressed are largely unknown. We found pervasive DNA damage in hematologic malignancies, including multiple myeloma, lymphoma and leukemia, which leads to activation of a p53-independent, proapoptotic network centered on nuclear relocalization of ABL1 kinase. Although nuclear ABL1 triggers cell death through its interaction with the Hippo pathway coactivator YAP1 in normal cells, we show that low YAP1 levels prevent nuclear ABL1-induced apoptosis in these hematologic malignancies. YAP1 is under the control of a serine-threonine kinase, STK4. Notably, genetic inactivation of STK4 restores YAP1 levels, triggering cell death in vitro and in vivo. Our data therefore identify a new synthetic-lethal strategy to selectively target cancer cells presenting with endogenous DNA damage and low YAP1 levels. C1 [Cottini, Francesca; Hideshima, Teru; Richardson, Paul G.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Cottini, Francesca; Dori, Martina; Antonini, Elena; Tonon, Giovanni] Ist Ricovero & Cura Carattere Sci IRCCS San Raffa, Div Mol Oncol, Funct Genom Canc Unit, Milan, Italy. [Xu, Chunxiao; Sattler, Martin; Carrasco, Ruben; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Xu, Chunxiao; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Xu, Chunxiao; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Dana Farber Canc Inst, Boston, MA USA. [Agnelli, Luca; Neri, Antonino] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Hematol Unit, Milan, Italy. [ten Hacken, Elisa; Bertilaccio, Maria Teresa; Caigaris-Cappio, Federico] IRCCS San Raffaele Sci Inst, Div Mol Oncol, Lab Lymphoid Malignancies, Milan, Italy. [Ponzoni, Maurilio] IRCCS San Raffaele Sci Inst, Myeloma Unit, Pathol Unit, Milan, Italy. [Marcatti, Magda] IRCCS San Raffaele Sci Inst, Myeloma Unit, Dept Hematol Oncol, Hematol & Bone Marrow Transplantat Unit, Milan, Italy. [Kimmelman, Alec C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. [Caigaris-Cappio, Federico; Tonon, Giovanni] Univ Vita Salute San Raffaele, Milan, Italy. [Caigaris-Cappio, Federico; Tonon, Giovanni] IRCCS San Raffaele Sci Inst, MAGIC Microenvironm & Genes Canc Blood Interdiv R, Milan, Italy. [Blandino, Giovanni] Italian Natl Canc Inst Regina Elena, Translat Oncogen Unit, Rome, Italy. [Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu; tonon.giovanni@hsr.it OI neri, antonino/0000-0001-9047-5912 FU Fondazione CARIPLO, a Marie Curie International Reintegration Grant; Associazione Raliana per la Ricerca sul Cancro (AIRC); Special Program Molecular Clinical Oncology [9965]; NIH [P50100707, PO-1 78378, RO-1 50947] FX We thank M. Sudol (Mount Sinai School of Medicine) for the eGFP-YAP1 construct, W Hahn (Dana-Farber Cancer Institute) for pLKO.1 shRNA lentiviral vectors and S. Rosen (Northwestern University) and R. Burger (University of Kiel) for MM.1R and INA-6 MM cells. We also thank E. Di Cairano and L. Spagnuolo for immunohistochemical stains, F. Ghini and A.M. Gasparri for technical help, the Dana-Farber Cancer Institute Flow cytometry facility, D. Kufe and F. Bernassola for insightful suggestions, C. Brennan for the bioinformatics analysis and members of the Anderson and Tonon lab for sharing reagents and critical reading of the manuscript. W.M.K. is supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. This work was supported by Fondazione CARIPLO, a Marie Curie International Reintegration Grant and the Associazione Raliana per la Ricerca sul Cancro (AIRC; AIRC Special Program Molecular Clinical Oncology, 5 per milk no. 9980 to A.N. and Investigator Grants and Special Program Molecular Clinical Oncology, 5 per mile no. 9965 to G.T.) (G.T.). K.C.A. is an American Cancer Society Clinical Research Professor and is supported by NIH grants NIH SPORE P50100707, PO-1 78378 and RO-1 50947. NR 38 TC 54 Z9 56 U1 4 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JUN PY 2014 VL 20 IS 6 BP 599 EP 606 DI 10.1038/nm.3562 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AI7LB UT WOS:000337071000021 PM 24813251 ER PT J AU Van Allen, EM Wagle, N Stojanov, P Perrin, DL Cibulskis, K Marlow, S Jane-Valbuena, J Friedrich, DC Kryukov, G Carter, SL McKenna, A Sivachenko, A Rosenberg, M Kiezun, A Voet, D Lawrence, M Lichtenstein, LT Gentry, JG Huang, FW Fostel, J Farlow, D Barbie, D Gandhi, L Lander, ES Gray, SW Joffe, S Janne, P Garber, J MacConaill, L Lindeman, N Rollins, B Kantoff, P Fisher, SA Gabriel, S Getz, G Garraway, LA AF Van Allen, Eliezer M. Wagle, Nikhil Stojanov, Petar Perrin, Danielle L. Cibulskis, Kristian Marlow, Sara Jane-Valbuena, Judit Friedrich, Dennis C. Kryukov, Gregory Carter, Scott L. McKenna, Aaron Sivachenko, Andrey Rosenberg, Mara Kiezun, Adam Voet, Douglas Lawrence, Michael Lichtenstein, Lee T. Gentry, Jeff G. Huang, Franklin W. Fostel, Jennifer Farlow, Deborah Barbie, David Gandhi, Leena Lander, Eric S. Gray, Stacy W. Joffe, Steven Janne, Pasi Garber, Judy MacConaill, Laura Lindeman, Neal Rollins, Barrett Kantoff, Philip Fisher, Sheila A. Gabriel, Stacey Getz, Gad Garraway, Levi A. TI Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine SO NATURE MEDICINE LA English DT Article ID SOMATIC MUTATIONS; LUNG ADENOCARCINOMA; LANDSCAPE; GENOME; HETEROGENEITY; CARCINOMA; SPECIMENS; PLATFORM; CATALOG; TISSUE AB Translating whole-exome sequencing (WES) for prospective clinical use may have an impact on the care of patients with cancer; however, multiple innovations are necessary for clinical implementation. These include rapid and robust WES of DNA derived from formalin-fixed, paraffin-embedded tumor tissue, analytical output similar to data from frozen samples and clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival formalin-fixed, paraffin-embedded tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a 'long tail' of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15 out of 16 patients. In one patient, previously undetected findings guided clinical trial enrollment, leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine. C1 [Van Allen, Eliezer M.; Wagle, Nikhil; Stojanov, Petar; Marlow, Sara; Jane-Valbuena, Judit; Huang, Franklin W.; Barbie, David; Gandhi, Leena; Gray, Stacy W.; Joffe, Steven; Janne, Pasi; Garber, Judy; MacConaill, Laura; Lindeman, Neal; Rollins, Barrett; Kantoff, Philip; Garraway, Levi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Van Allen, Eliezer M.; Wagle, Nikhil; Stojanov, Petar; Perrin, Danielle L.; Cibulskis, Kristian; Marlow, Sara; Jane-Valbuena, Judit; Friedrich, Dennis C.; Kryukov, Gregory; Carter, Scott L.; McKenna, Aaron; Sivachenko, Andrey; Rosenberg, Mara; Kiezun, Adam; Voet, Douglas; Lawrence, Michael; Lichtenstein, Lee T.; Gentry, Jeff G.; Huang, Franklin W.; Fostel, Jennifer; Farlow, Deborah; Lander, Eric S.; Fisher, Sheila A.; Gabriel, Stacey; Getz, Gad; Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA USA. [McKenna, Aaron] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Joffe, Steven] Childrens Hosp Boston, Boston, MA USA. [MacConaill, Laura; Lindeman, Neal] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Garraway, LA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM gadgetz@broadinstitute.org; levi_garraway@dfci.harvard.edu RI Kryukov, Gregory/A-9592-2008; OI Gandhi, Leena/0000-0002-2398-9179; Joffe, Steven/0000-0002-0667-7384 FU Chair in Oncology at Massachusetts General Hospital; Starr Cancer Foundation; Prostate Cancer Foundation; US National Institutes of Health (NIH) NHGRI Clinical Sequencing Exploratory Research grant [1U01HG006492]; NIH National Cancer Institute [1U24CA126546]; US Department of Defense; NIH [U24CA143845]; Dana-Farber Leadership Council FX We thank the patients and clinicians for their participation in this project. We thank the Broad Genomics Platform (specifically K. Anderka, A. Cheney, E. Wheeler, T. Mason and C. Crawford). We thank C. Sougnez for facilitating data deposition. We also thank A. Lane and A. Yoda (Dana-Farber Cancer Institute), for their contributions to the JAK3 experimental work: A. Lane provided Ba/F3 cells, and A. Yoda provided murine stem cell virus puromycin vector. G.G. is partially funded by a Paul C. Zamecnik, MD, Chair in Oncology at Massachusetts General Hospital. This work was supported by the Starr Cancer Foundation (L.A.G.), the Prostate Cancer Foundation (E.M.V.A. and L.A.G.), US National Institutes of Health (NIH) NHGRI Clinical Sequencing Exploratory Research grant 1U01HG006492 (L.A.G.), the NIH National Cancer Institute grant 1U24CA126546 (L.A.G. and E.S.L.), the US Department of Defense (L.A.G.), NIH U24CA143845 grant (G.G.) and the Dana-Farber Leadership Council (E.M.V.A.). NR 39 TC 123 Z9 123 U1 7 U2 37 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JUN PY 2014 VL 20 IS 6 BP 682 EP 688 DI 10.1038/nm.3559 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA AI7LB UT WOS:000337071000033 PM 24836576 ER PT J AU Guyette, JP Gilpin, SE Charest, JM Tapias, LF Ren, X Ott, HC AF Guyette, Jacques P. Gilpin, Sarah E. Charest, Jonathan M. Tapias, Luis F. Ren, Xi Ott, Harald C. TI Perfusion decellularization of whole organs SO NATURE PROTOCOLS LA English DT Article ID STEM-CELL DIFFERENTIATION; LUNG DE-CELLULARIZATION; SODIUM DODECYL-SULFATE; EXTRACELLULAR-MATRIX; HEART-VALVES; IN-VITRO; ORTHOTOPIC TRANSPLANTATION; MECHANICAL-PROPERTIES; RE-CELLULARIZATION; PORCINE KIDNEYS AB The native extracellular matrix (ECM) outlines the architecture of organs and tissues. It provides a unique niche of composition and form, which serves as a foundational scaffold that supports organ-specific cell types and enables normal organ function. Here we describe a standard process for pressure-controlled perfusion decellularization of whole organs for generating acellular 3D scaffolds with preserved ECM protein content, architecture and perfusable vascular conduits. By applying antegrade perfusion of detergents and subsequent washes to arterial vasculature at low physiological pressures, successful decellularization of complex organs (i.e., hearts, lungs and kidneys) can be performed. By using appropriate modifications, pressure-controlled perfusion decellularization can be achieved in small-animal experimental models (rat organs, 4-5 d) and scaled to clinically relevant models (porcine and human organs, 12-14 d). Combining the unique structural and biochemical properties of native acellular scaffolds with subsequent recellularization techniques offers a novel platform for organ engineering and regeneration, for experimentation ex vivo and potential clinical application in vivo. C1 [Guyette, Jacques P.; Gilpin, Sarah E.; Charest, Jonathan M.; Ren, Xi; Ott, Harald C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Guyette, Jacques P.; Gilpin, Sarah E.; Tapias, Luis F.; Ren, Xi; Ott, Harald C.] Harvard Univ, Sch Med, Boston, MA USA. [Tapias, Luis F.; Ott, Harald C.] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Ott, Harald C.] Harvard Stem Cell Inst, Boston, MA USA. RP Ott, HC (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. EM hott@mgh.harvard.edu FU US National Institutes of Health (NIH) [DP2 0D008749-01, R21 HL108663-01, R01 HL108678]; Department of Surgery, Massachusetts General Hospital; Harvard Stem Cell Institute; United Therapeutics Inc. FX The present study was supported by the US National Institutes of Health (NIH) Director's New Innovator Award DP2 0D008749-01, grants R21 HL108663-01 and R01 HL108678, by seed grants by the Department of Surgery, Massachusetts General Hospital and the Harvard Stem Cell Institute, and a research grant by United Therapeutics Inc. We thank D.J. Mathisen and J.P. Vacanti for their mentorship and senior advice on surgical procedures, tissue engineering aspects and for critical review of the manuscript. NR 54 TC 38 Z9 40 U1 4 U2 47 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 EI 1750-2799 J9 NAT PROTOC JI Nat. Protoc. PD JUN PY 2014 VL 9 IS 6 BP 1451 EP 1468 DI 10.1038/nprot.2014.097 PG 18 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA AI8FS UT WOS:000337145800018 PM 24874812 ER PT J AU Kim, MN Edlow, BL Durduran, T Frangos, S Mesquita, RC Levine, JM Greenberg, JH Yodh, AG Detre, JA AF Kim, Meeri N. Edlow, Brian L. Durduran, Turgut Frangos, Suzanne Mesquita, Rickson C. Levine, Joshua M. Greenberg, Joel H. Yodh, Arjun G. Detre, John A. TI Continuous Optical Monitoring of Cerebral Hemodynamics During Head-of-Bed Manipulation in Brain-Injured Adults SO NEUROCRITICAL CARE LA English DT Article DE Diffuse correlation spectroscopy; Near-infrared spectroscopy; Diffuse optical spectroscopy; Head-of-bed; Cerebral blood flow; Neurocritical care; Cerebral hemodynamics ID DIFFUSE CORRELATION SPECTROSCOPY; ANEURYSMAL SUBARACHNOID HEMORRHAGE; TRANSCRANIAL DOPPLER ULTRASOUND; BLOOD-FLOW; PERFUSION-PRESSURE; INTRACRANIAL-PRESSURE; AUTOREGULATION; RESPONSES; CIRCULATION; VALIDATION AB Head-of-bed manipulation is commonly performed in the neurocritical care unit to optimize cerebral blood flow (CBF), but its effects on CBF are rarely measured. This pilot study employs a novel, non-invasive instrument combining two techniques, diffuse correlation spectroscopy (DCS) for measurement of CBF and near-infrared spectroscopy (NIRS) for measurement of cerebral oxy- and deoxy-hemoglobin concentrations, to monitor patients during head-of-bed lowering. Ten brain-injured patients and ten control subjects were monitored continuously with DCS and NIRS while the head-of-bed was positioned first at 30A degrees and then at 0A degrees. Relative CBF (rCBF) and concurrent changes in oxy- (Delta HbO(2)), deoxy- (Delta Hb), and total-hemoglobin concentrations (Delta THC) from left/right frontal cortices were monitored for 5 min at each position. Patient and control response differences were assessed. rCBF, Delta HbO(2), and Delta THC responses to head lowering differed significantly between brain-injured patients and healthy controls (P < 0.02). For patients, rCBF changes were heterogeneous, with no net change observed in the group average (0.3 +/- A 28.2 %, P = 0.938). rCBF increased in controls (18.6 +/- A 9.4 %, P < 0.001). Delta HbO(2), Delta Hb, and Delta THC increased with head lowering in both groups, but to a larger degree in brain-injured patients. rCBF correlated moderately with changes in cerebral perfusion pressure (R = 0.40, P < 0.001), but not intracranial pressure. DCS/NIRS detected differences in CBF and oxygenation responses of brain-injured patients versus controls during head-of-bed manipulation. This pilot study supports the feasibility of continuous bedside measurement of cerebrovascular hemodynamics with DCS/NIRS and provides the rationale for further investigation in larger cohorts. C1 [Kim, Meeri N.; Yodh, Arjun G.] Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. [Edlow, Brian L.; Levine, Joshua M.; Greenberg, Joel H.; Detre, John A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Edlow, Brian L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Durduran, Turgut] Mediterranean Technol Pk, ICFO Inst Ciencies Foton, Barcelona 08860, Spain. [Frangos, Suzanne; Levine, Joshua M.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. [Mesquita, Rickson C.] Univ Campinas UNICAMP, Inst Phys, BR-13083859 Campinas, SP, Brazil. [Detre, John A.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RP Kim, MN (reprint author), Univ Penn, Dept Phys & Astron, 209 South 33rd St, Philadelphia, PA 19104 USA. EM meeri@alumni.upenn.edu RI FAPESP, BRAINN/J-4049-2015; Durduran, Turgut/N-7768-2015; Inst. of Physics, Gleb Wataghin/A-9780-2017; OI Durduran, Turgut/0000-0001-5838-1027; Mesquita, Rickson/0000-0003-1945-6713 FU National Institute of Heath [NS-054575, NS-060653, NS-045839, HL077699, RR-02305, R25-NS065743]; Fundacio Cellex Barcelona; Marie Curie IRG (FP7, RPTAMON); Institute de Salud Carlos III (DOMMON, FIS); Ministerio de Ciencia e Innovacion (MICINN); Ministerio de Economia y Comepetitividad; Institucio CERCA (DOCNEURO) [PROVAT-002-11]; Generalitat de Catalunya, European Regional Development Fund (FEDER/ERDF); LASERLAB (FP7); Photonics4Life (FP7) consortia FX Sources of Support (if applicable): Name(s) of Grantor(s), Grant or contract numbers, name of author who received the funding, and specific material support given: National Institute of Heath: NS-054575 (JAD), NS-060653 (AGY), NS-045839 (JAD), HL077699 (AGY), RR-02305 (AGY, JAD), R25-NS065743 (BLE). TD gratefully acknowledged partial support by Fundacio Cellex Barcelona, Marie Curie IRG (FP7, RPTAMON), Institute de Salud Carlos III (DOMMON, FIS), Ministerio de Ciencia e Innovacion (MICINN), Ministerio de Economia y Comepetitividad, Institucio CERCA (DOCNEURO, PROVAT-002-11), Generalitat de Catalunya, European Regional Development Fund (FEDER/ERDF) and LASERLAB (FP7) and Photonics4Life (FP7) consortia. University of Pennsylvania Research Foundation (JHG). Financial Disclosure AGY, JAD, JHG, TD are co-inventors on patents related to the optical technology. However, they do not receive any income or royalties from those patents. NR 52 TC 12 Z9 12 U1 0 U2 15 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD JUN PY 2014 VL 20 IS 3 BP 443 EP 453 DI 10.1007/s12028-013-9849-7 PG 11 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA AI7RH UT WOS:000337092900013 PM 23653267 ER PT J AU Qureshi, AI Majidi, S Gilani, WI Palesch, YY Martin, R Novitzke, J Cruz-Flores, S Ehtisham, A Goldstein, JN Kirmani, JF Hussein, HM Suri, MFK Tariq, N AF Qureshi, Adnan I. Majidi, Shahram Gilani, Waqas I. Palesch, Yuko Y. Martin, Renee Novitzke, Jill Cruz-Flores, Salvador Ehtisham, Asad Goldstein, Joshua N. Kirmani, Jawad F. Hussein, Haitham M. Suri, M. Fareed K. Tariq, Nauman TI Increased Brain Volume Among Good Grade Patients with Intracerebral Hemorrhage. Results from the Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH) Study SO NEUROCRITICAL CARE LA English DT Article DE Intracerebral hemorrhage; Edema; Computed tomography; Brain volume ID PERIHEMATOMAL EDEMA; ACUTE STROKE; RAT MODEL; INJURY AB We ascertained the occurrence of global cerebral edema manifesting as increased brain volume in subjects with intracerebral hemorrhage (ICH) and explored the relationship between subject characteristics and three month outcomes. A post-hoc analysis of a multicenter prospective study that recruited patients with ICH, elevated SBP a parts per thousand yen170 mm Hg, and Glasgow Coma Scale (GCS) score a parts per thousand yen8, who presented within 6 h of symptom onset was performed. Computed tomographic (CT) scans at baseline and 24 h, submitted to a core image laboratory, were analyzed to measure total brain, hematoma, and perihematoma edema volumes from baseline and 24-h CT scans using image analysis software. The increased brain volume was determined by subtracting the hematoma and perihematomal edema volumes from the total brain volume. A total of 18 (44 %) of 41 subjects had increased brain volume that developed between initial CT scan and 24-h CT scan. The median increase in brain volume among the 18 subjects was 35 cc ranging from 0.12 to 296 cc. The median baseline GCS score was 15 in both groups of subjects who experienced increased brain volume and those who did not, and the median hematoma volume was 10.18 and 6.73, respectively. Three of the 18 subjects with increased brain volume underwent concurrent neurological deterioration and one subject died during hospitalization. We found preliminary evidence of increased cerebral brain volume in subjects with good grade and small ICHs, which may be suggestive of global cerebral edema. C1 [Qureshi, Adnan I.; Majidi, Shahram; Gilani, Waqas I.; Novitzke, Jill; Suri, M. Fareed K.; Tariq, Nauman] Univ Minnesota, Zeenat Qureshi Stroke Res Ctr, Minneapolis, MN 55455 USA. [Palesch, Yuko Y.; Martin, Renee] Med Univ S Carolina, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Cruz-Flores, Salvador] St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. [Ehtisham, Asad] Univ Mississippi, Med Ctr, Dept Neurol, Jackson, MS 39216 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Kirmani, Jawad F.] John F Kennedy Med Ctr, Neurosci Inst, Edison, NJ USA. [Hussein, Haitham M.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Qureshi, AI (reprint author), Univ Minnesota, Zeenat Qureshi Stroke Res Ctr, 420 Delaware St SE,MMC 295, Minneapolis, MN 55455 USA. EM aiqureshi@hotmail.com RI Goldstein, Joshua/H-8953-2016 FU National Institutes of Health [RO1-NS44976-01A2]; American Heart Association [0840053N]; National Institute of Health [U01-NS062091-01A2]; Minnesota Medical Foundation, Minneapolis, MN FX Dr. Qureshi has received funding from the National Institutes of Health RO1-NS44976-01A2 (medication provided by ESP Parma), American Heart Association Established Investigator Award 0840053N, National Institute of Health U01-NS062091-01A2, and the Minnesota Medical Foundation, Minneapolis, MN. NR 25 TC 5 Z9 5 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD JUN PY 2014 VL 20 IS 3 BP 470 EP 475 DI 10.1007/s12028-013-9842-1 PG 6 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA AI7RH UT WOS:000337092900017 PM 23609118 ER PT J AU Moonen, AJH Wijers, A Leentjens, AFG Christine, CW Factor, SA Juncos, J Lyness, JM Marsh, L Panisset, M Pfeiffer, R Rottenberg, D Ramos, CS Shulman, L Singer, C Slevin, J McDonald, W Auinger, P Richard, IH AF Moonen, A. J. H. Wijers, A. Leentjens, A. F. G. Christine, C. W. Factor, S. A. Juncos, J. Lyness, J. M. Marsh, L. Panisset, M. Pfeiffer, R. Rottenberg, D. Ramos, C. Serrano Shulman, L. Singer, C. Slevin, J. McDonald, W. Auinger, P. Richard, I. H. TI Severity of depression and anxiety are predictors of response to antidepressant treatment in Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Depression; Clinical trials randomized controlled; Venlafaxine; Paroxetine ID DATABASE; PLACEBO AB Background: Antidepressants have appeared to be more effective than placebo treatment in treating depressive syndromes in patients with Parkinson's disease (PD). Objective: To identify factors that predict improvement in depressive symptoms during antidepressant treatment in depressed PD patients. Methods: A secondary analysis was performed on the dataset of the Randomized Placebo-controlled Study of Antidepressants in PD (SAD-PD), in which 76 patients received active treatment with either paroxetine or venlafaxine extended release (XR), and 39 patients received placebo treatment. Backward stepwise regression analyses were conducted with change in 24-item Hamilton Depression Rating Scale (HAMD-24) score between assessments at baseline and week 12 as the main outcome measure, and sex, age, baseline HAMD-24 score, Unified Parkinson's Disease Rating Scale section III (UPDRS-III) score, Mini-Mental State Examination (MMSE), and the Clinical Anxiety Scale (CAS) as independent variables. Results: In both the active treatment and placebo groups, higher baseline HAMD-24 score and lower UPDRS-III score were associated with greater reduction in HAMD-24 score. Higher anxiety scores predicted less response in the active treatment group. Higher MMSE scores predicted greater response only in the placebo-treated group. Sex and age were no predictors of response. Conclusions: Higher pre-treatment depression scores and lower pre-treatment anxiety scores are the two most important predictors for improvement during antidepressant treatment in depressed PD patients, which is in line with those found in treatment studies of depressed non-PD patients. Furthermore, our results indicate the requirement for different or more intensive treatment for depressed PD patients with more severe anxiety symptoms. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Moonen, A. J. H.; Wijers, A.; Leentjens, A. F. G.] Maastricht Univ, Dept Psychiat, NL-6200 MD Maastricht, Netherlands. [Christine, C. W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Factor, S. A.; Juncos, J.] Emory Univ, Dept Neurol, Atlanta, GA USA. [McDonald, W.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Marsh, L.] Michael E DeBakey Vet Adm Med Ctr, Houston, TX USA. [Marsh, L.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Marsh, L.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Panisset, M.] Univ Montreal, Dept Neurol, Montreal, PQ, Canada. [Pfeiffer, R.] Univ Tennessee, Dept Neurol, Hlth Sci Ctr, Memphis, TN USA. [Rottenberg, D.] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. [Rottenberg, D.] Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. [Ramos, C. Serrano] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Shulman, L.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Singer, C.] Univ Miami, Dept Neurol, Leonard M Miller Sch Med, Miami, FL USA. [Slevin, J.] Univ Kentucky, Coll Med, Dept Neurol, Lexington, KY USA. [Lyness, J. M.; Auinger, P.; Richard, I. H.] Univ Rochester, Sch Med & Dent, Rochester, NY USA. RP Moonen, AJH (reprint author), Maastricht Univ, Dept Psychiat, POB 616, NL-6200 MD Maastricht, Netherlands. EM anja.moonen@maastrichtuniversity.nl FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [R01 N5046487]; General Clinical Research Center at Johns Hopkins University School of Medicine (National Center for Research Resources/NIH) [M01-RR00052] FX This study was funded by National Institutes of Health/National Institute of Neurological Disorders and Stroke grant R01 N5046487 and the General Clinical Research Center at Johns Hopkins University School of Medicine (National Center for Research Resources/NIH M01-RR00052). Wyeth Pharmaceuticals provided venlafaxine extended release and matching placebo. Glaxo-Smith-Kline provided paroxetine. NR 10 TC 5 Z9 6 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 EI 1873-5126 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JUN PY 2014 VL 20 IS 6 BP 644 EP 646 DI 10.1016/j.parkreldis.2014.02.025 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA AI5AN UT WOS:000336877900016 PM 24679737 ER PT J AU Khodjaev, SD Teerlink, JR Malik, FI AF Khodjaev, Soidjon D. Teerlink, John R. Malik, Fady I. TI Novel drug mechanisms in development for heart failure SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review DE BAY 94-8862; Heart failure; LCZ696; Omecamtiv mecarbil; Pharmacologic therapy; Serelaxin; TRV 027; Ularitide ID CARDIAC MYOSIN ACTIVATOR; DOUBLE-BLIND; MINERALOCORTICOID RECEPTOR; OMECAMTIV-MECARBIL; NATRIURETIC PEPTIDES; CONTROLLED-TRIAL; HORMONE RELAXIN; BAY 94-8862; TASK-FORCE; URODILATIN AB Heart failure therapy has seen many advances over the last 40 years and has rapidly expanded beyond diuretics and digoxin to include several new mechanisms of action and devices whose efficacy had been demonstrated in large clinical trials. The evidence for their use is thoroughly summarized and discussed in current heart failure treatment guidelines and is not the subject of this review. Despite these advances, the mortality and morbidity in heart failure patients is still substantial, and there remains a need to develop new heart failure therapies. Recognizing that advances in medical therapy are often driven by the introduction of drugs with novel mechanisms of action, here we provide an overview of investigative heart failure drugs with novel mechanisms of action that are the subject of ongoing clinical trials. C1 [Khodjaev, Soidjon D.; Teerlink, John R.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. [Khodjaev, Soidjon D.; Teerlink, John R.; Malik, Fady I.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Malik, Fady I.] Cytokinet Inc, Res & Early Dev, San Francisco, CA USA. RP Teerlink, JR (reprint author), San Francisco VA Med Ctr, Cardiol Sect, 111C,4150 Clement St, San Francisco, CA 94121 USA. EM john.teerlink@ucsf.edu NR 42 TC 0 Z9 0 U1 3 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 EI 1432-2013 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD JUN PY 2014 VL 466 IS 6 BP 1219 EP 1225 DI 10.1007/s00424-014-1528-9 PG 7 WC Physiology SC Physiology GA AI4AO UT WOS:000336807700018 PM 24793049 ER PT J AU Yang, ZR Wang, C Zhou, QX An, JL Hildebrandt, E Aleksandrov, LA Kappes, JC DeLucas, LJ Riordan, JR Urbatsch, IL Hunt, JF Brouillette, CG AF Yang, Zhengrong Wang, Chi Zhou, Qingxian An, Jianli Hildebrandt, Ellen Aleksandrov, Luba A. Kappes, John C. DeLucas, Lawrence J. Riordan, John R. Urbatsch, Ina L. Hunt, John F. Brouillette, Christie G. TI Membrane protein stability can be compromised by detergent interactions with the extramembranous soluble domains SO PROTEIN SCIENCE LA English DT Review DE CFTR; NBD1; DSC; CD; thermal unfolding; detergent interaction; membrane protein; extramembrane domain; soluble domain ID TRANSMEMBRANE CONDUCTANCE REGULATOR; NUCLEOTIDE-BINDING DOMAIN; DIFFERENTIAL SCANNING CALORIMETRY; CYSTIC-FIBROSIS MUTATION; CYTOCHROME-C-OXIDASE; FULL-LENGTH CFTR; DELTA-F508 MUTATION; SURFACTANT INTERACTIONS; ESCHERICHIA-COLI; EFFICIENT PURIFICATION AB Detergent interaction with extramembranous soluble domains (ESDs) is not commonly considered an important determinant of integral membrane protein (IMP) behavior during purification and crystallization, even though ESDs contribute to the stability of many IMPs. Here we demonstrate that some generally nondenaturing detergents critically destabilize a model ESD, the first nucleotide-binding domain (NBD1) from the human cystic fibrosis transmembrane conductance regulator (CFTR), a model IMP. Notably, the detergents show equivalent trends in their influence on the stability of isolated NBD1 and full-length CFTR. We used differential scanning calorimetry (DSC) and circular dichroism (CD) spectroscopy to monitor changes in NBD1 stability and secondary structure, respectively, during titration with a series of detergents. Their effective harshness in these assays mirrors that widely accepted for their interaction with IMPs, i.e., anionic>zwitterionic>nonionic. It is noteworthy that including lipids or nonionic detergents is shown to mitigate detergent harshness, as will limiting contact time. We infer three thermodynamic mechanisms from the observed thermal destabilization by monomer or micelle: (i) binding to the unfolded state with no change in the native structure (all detergent classes); (ii) native state binding that alters thermodynamic properties and perhaps conformation (nonionic detergents); and (iii) detergent binding that directly leads to denaturation of the native state (anionic and zwitterionic). These results demonstrate that the accepted model for the harshness of detergents applies to their interaction with an ESD. It is concluded that destabilization of extramembranous soluble domains by specific detergents will influence the stability of some IMPs during purification. C1 [Yang, Zhengrong; Brouillette, Christie G.] Univ Alabama Birmingham, Dept Chem, Birmingham, AL 35294 USA. [Yang, Zhengrong; Zhou, Qingxian; An, Jianli; DeLucas, Lawrence J.; Brouillette, Christie G.] Univ Alabama Birmingham, Struct Biol Ctr, Birmingham, AL USA. [Wang, Chi; Hunt, John F.] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. [Hildebrandt, Ellen; Urbatsch, Ina L.] Texas Tech Univ, Hlth Sci Ctr, Dept Cell Biol & Biochem, Lubbock, TX 79430 USA. [Aleksandrov, Luba A.; Riordan, John R.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA. [Aleksandrov, Luba A.; Riordan, John R.] Univ N Carolina, Cyst Fibrosis Treatment & Res Ctr, Chapel Hill, NC USA. [Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. [DeLucas, Lawrence J.] Univ Alabama Birmingham, Dept Optometry, Birmingham, AL USA. [Urbatsch, Ina L.] Texas Tech Univ, Hlth Sci Ctr, Ctr Membrane Prot Res, Lubbock, TX 79430 USA. RP Brouillette, CG (reprint author), 1025 18th St South,234 CBSE, Birmingham, AL 35294 USA. EM jfhunt@biology.columbia.edu; christie@uab.edu FU CFFT; NIH [R01 DK051619, R0 1DK051870, P01 HL110873]; Shared Facility Program of the UAB Comprehensive Cancer Center [316851] FX Grant sponsor: CFFT (to C. B., J.H., I. U., J.R., L. D., and J.K.). Grant sponsor: NIH R01 DK051619; R0 1DK051870; P01 HL110873 (to J.R.). Grant sponsor: Shared Facility Program of the UAB Comprehensive Cancer Center; Grant number: 316851. NR 102 TC 11 Z9 11 U1 2 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD JUN PY 2014 VL 23 IS 6 BP 769 EP 789 DI 10.1002/pro.2460 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AI4NW UT WOS:000336843100010 PM 24652590 ER PT J AU Halpern, EF AF Halpern, Elkan F. TI Behind the Numbers: Inverse Probability Weighting SO RADIOLOGY LA English DT Editorial Material AB Inverse probability weighting is a propensity score-based technique that can be used to compensate for imbalance in study groups. It is an alternative to regression-based adjustment of the outcomes. It has advantages over matching of cases on the basis of propensity scores when there are more than two groups to compare, when finding matches results in insufficient sample sizes, or when the data are censored. However, it can create artificial imbalance unless it is applied carefully. In this article, an introduction to inverse probability weighting is provided by using the Yang et al study published in this issue of Radiology as an example. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Halpern, EF (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St, Boston, MA 02114 USA. EM elk@mgh-ita.org NR 6 TC 3 Z9 3 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2014 VL 271 IS 3 BP 625 EP 628 DI 10.1148/radiol.14140035 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI5GW UT WOS:000336894600002 PM 24848956 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI A New Era in Mammography Screening SO RADIOLOGY LA English DT Editorial Material ID DIGITAL BREAST TOMOSYNTHESIS; CANCER; WOMEN; CALCIFICATIONS; EXPERIENCE; VIEWS; TIME C1 Harvard Univ, Dept Radiol, Breast Imaging Div, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Dept Radiol, Breast Imaging Div, Massachusetts Gen Hosp,Sch Med, 15 Parkman St,Ambulatory Care Bldg,Suite 219, Boston, MA 02114 USA. EM dkopans@partners.org NR 31 TC 2 Z9 2 U1 0 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2014 VL 271 IS 3 BP 629 EP 631 DI 10.1148/radiol.14140177 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI5GW UT WOS:000336894600003 PM 24848957 ER PT J AU Sheth, RA Heidari, P Esfahani, SA Wood, BJ Mahmood, U AF Sheth, Rahul A. Heidari, Pedram Esfahani, Shadi A. Wood, Bradford J. Mahmood, Umar TI Interventional Optical Molecular Imaging Guidance during Percutaneous Biopsy SO RADIOLOGY LA English DT Article ID INDOCYANINE GREEN; FLUORESCENCE; ENDOSCOPY AB Purpose: To investigate indocyanine green (ICG) as a molecular beacon for malignant lesions within the liver and evaluate the ability of a developed handheld imaging system to allow measurement of ICG fluorescence within focal hepatic lesions with high target-to-background ratios in a mouse model. Materials and Methods: All animal experiments were approved by the institutional animal care committee. A handheld optical molecular imaging device was constructed to pass through the introducer needle of a standard percutaneous biopsy kit. An ex vivo phantom system was constructed to quantify tissue attenuation properties of ICG in liver parenchyma. Subsequently, intrahepatic colorectal cancer metastases were generated in nude mice, and epifluorescence imaging of ICG, as well as histologic analysis of the explanted livers, was performed at 3 weeks after implantation (n = 6). Epifluorescence imaging with the handheld imaging device was then performed on intrahepatic colorectal metastases after the administration of ICG (n = 15) at 3, 6, and 24 hours after injection. Target-to-background ratios were calculated for each time point. Subsequently, a core biopsy of intrahepatic colorectal metastases was performed by using a standard clinical 18-gauge biopsy needle. Results: There was avid localization of ICG to the focal lesions at all time points. Similarly, fluorescence within the tumors was greater than that within normal liver, as detected with the handheld imaging system (mean target-to-background ratio +/- standard deviation, 3.9 +/- 0.2 at 24 hours). A core biopsy of tumor and normal adjacent liver by using a standard biopsy needle demonstrated a sharp margin of fluorescence intensity at the tumor-liver interface. Conclusion: The custom-designed molecular imaging device, in combination with ICG, readily allowed differentiation between normal and malignant tissue in a murine model of intrahepatic colorectal metastasis. (C) RSNA, 2014 C1 [Sheth, Rahul A.; Heidari, Pedram; Esfahani, Shadi A.; Mahmood, Umar] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA. [Wood, Bradford J.] Ctr Clin, Ctr Intervent Oncol Radiol & Imaging Sci, Bethesda, MD USA. [Wood, Bradford J.] NCI, NIH, Bethesda, MD 20892 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA. EM umah-mood@mgh.harvard.edu FU National Institutes of Health [U01CA084301] FX This research was supported by the National Institutes of Health (grant U01CA084301). NR 14 TC 10 Z9 13 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2014 VL 271 IS 3 BP 770 EP 777 DI 10.1148/radiol.14131880 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI5GW UT WOS:000336894600018 PM 24520946 ER PT J AU Davis, LA Whitfield, E Cannon, GW Wolff, RK Johnson, DS Reimold, AM Kerr, GS Richards, JS Mikuls, TR Caplan, L AF Davis, Lisa A. Whitfield, Emily Cannon, Grant W. Wolff, Roger K. Johnson, Dannette S. Reimold, Andreas M. Kerr, Gail S. Richards, J. Steuart Mikuls, Ted R. Caplan, Liron TI Association of rheumatoid arthritis susceptibility gene with lipid profiles in patients with rheumatoid arthritis SO RHEUMATOLOGY LA English DT Article DE arthritis; rheumatoid; polymorphism; single nucleotide; cholesterol; HDL; LDL; triglycerides ID NF-KAPPA-B; DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR RISK-FACTORS; C-REL; DISEASE SUSCEPTIBILITY; MYOCARDIAL-INFARCTION; VASCULAR-DISEASE; NUCLEAR-FACTOR; POLYMORPHISM; TRANSCRIPTION AB Objective. RA patients have an increased risk of cardiovascular (CV) disease, although the mechanisms are unclear. As RA and CV disease may be associated through lipid profiles, we examined whether single nucleotide polymorphisms (SNPs) associated with RA susceptibility were associated with low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG) levels in RA subjects. Methods. Patients (n = 763) enrolled in the Veterans Affairs RA registry who were not on hydroxymethyl-glutaryl-CoA reductase inhibitor were genotyped for human leukocyte antigen shared epitope (HLA-DRB1-SE) and SNPs in the following genes: CTLA-4 (cytotoxic T-lymphocyte antigen 4), IL-10, PTPN22 (protein tyrosine phosphatase, non-receptor type 22), REL (c-Rel), STAT4 (signal transducer and activator of transcription protein), TNF-alpha and TRAF1 (TNF receptor-associated factor 1). Other covariates included patient characteristics (age, gender, race, smoking status, education, BMI, modified Charlson-Deyo comorbidity index), CV characteristics (hypertension, diabetes, alcohol abuse), pharmacologic exposures (MTX, anti-TNF, glucocorticoids) and RA severity/activity markers (RA disease duration, mean DAS, CRP, RF positivity, anti-CCP positivity). Multivariate linear regression was performed to determine the factors associated with LDL, HDL and TG levels. Results. The REL SNP rs9309331 homozygous minor allele was associated with higher LDL levels. Caucasian race and increasing BMI were associated with lower HDL. Factors associated with higher TG were diabetes, Caucasian race and higher BMI. Conclusion. The REL SNP rs9309331 was associated with LDL levels in our study. This association is a possible explanation of the increased risk of RA patients for CV disease and requires further inquiry. C1 [Davis, Lisa A.] Univ Colorado, Sch Med, Dept Med, Div Rheumatol,Denver Hlth Med Ctr, Denver, CO USA. [Whitfield, Emily; Caplan, Liron] Univ Colorado, Sch Med, Dept Med, Div Rheumatol,Denver Vet Affairs Med Ctr VAMC, Denver, CO USA. [Davis, Lisa A.; Caplan, Liron] Univ Colorado, Sch Med, Dept Med, Div Rheumatol, Denver, CO USA. [Whitfield, Emily] Denver VAMC, Dept Res, Div Care Coordinat, Denver, CO USA. [Cannon, Grant W.] George E Wahlen VAMC, Staff Acad Affiliat, Salt Lake City, UT USA. [Cannon, Grant W.] Univ Utah, Sch Med, Dept Med, Div Rheumatol, Salt Lake City, UT USA. [Wolff, Roger K.] Univ Utah, Sch Med, Dept Internal Med, Div Epidemiol, Salt Lake City, UT USA. [Johnson, Dannette S.] Jackson VAMC, Med Serv, Rheumatol Sect, Jackson, MS USA. [Johnson, Dannette S.] Univ Mississippi, Dept Internal Med, Div Rheumatol & Mol Immunol, Jackson, MS 39216 USA. [Reimold, Andreas M.] Dallas VAMC, Med Serv, Rheumatol Sect, Dallas, TX USA. [Reimold, Andreas M.] Univ Texas Dallas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. [Kerr, Gail S.; Richards, J. Steuart] VAMC, Med Serv, Rheumatol Sect, Washington, DC USA. [Kerr, Gail S.; Richards, J. Steuart] Georgetown Univ, Dept Med, Div Rheumatol, Washington, DC USA. [Mikuls, Ted R.] Omaha VAMC, Med Serv, Rheumatol Sect, Omaha, NE USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Nebraska Arthrit Outcomes Res Ctr, Omaha, NE USA. RP Davis, LA (reprint author), Denver Hlth & Hosp Author, 777 Bannock St,MC 4000, Denver, CO 80204 USA. EM lisa.davis@ucdenver.edu FU Veterans Affairs Health Services Research and Development Grant [SHP 08-172]; University of Colorado Denver, Division of Rheumatology; National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases [T32 AR007534-24]; National Institutes of Health Loan Repayment Award; Rheumatology Research Foundation Rheumatology Scientist Development Award; Denver Health and Hospital Authority; University of Colorado; Colorado Clinical and Translational Science Institute; Veterans Affairs Health Services Research and Development Career Development Award [CDA 07-221] FX This work, including the genotyping, was supported by a Veterans Affairs Health Services Research and Development Grant (SHP 08-172) and the University of Colorado Denver, Division of Rheumatology. L.D. received support from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32 AR007534-24), National Institutes of Health Loan Repayment Award, the Rheumatology Research Foundation Rheumatology Scientist Development Award, Denver Health and Hospital Authority, the University of Colorado and the Colorado Clinical and Translational Science Institute. L.C. received support from a Veterans Affairs Health Services Research and Development Career Development Award (CDA 07-221). The funding sources had no role in the design, collection, analysis, interpretation of data, writing of the report or decision to submit this article 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 US government. All investigators participating in this research had access to all data. We declare that we (and our spouses, partners and children under 18 years of age) have no financial or personal relationships with other people or organizations that could inappropriately influence (bias) this work, including employment, consultancies, stock ownership, honoraria, paid expert testimony, patents or patent applications and travel grants, within 5 years of beginning the work submitted. NR 49 TC 5 Z9 5 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD JUN PY 2014 VL 53 IS 6 BP 1014 EP 1021 DI 10.1093/rheumatology/ket472 PG 8 WC Rheumatology SC Rheumatology GA AI6KJ UT WOS:000336982600008 PM 24489016 ER PT J AU Shinozaki, S Chang, K Sakai, M Shimizu, N Shimokado, K Stamler, J Kaneki, M AF Shinozaki, S. Chang, K. Sakai, M. Shimizu, N. Shimokado, K. Stamler, J. Kaneki, M. TI S-NITROSYLATION OF THE CXXC ZINC FINGER MOTIF IN SIRT1 MEDIATES AND ENHANCES NITROSATIVE STRESS IN ENDOTOXIN-INDUCED LIVER APOPTOSIS AND INFLAMMATION: PROTECTIVE ROLE OF S-NITROSOGLUTATHIONE REDUCTASE SO SHOCK LA English DT Meeting Abstract CT 37th Annual Conference of the Shock-Society on Shock CY JUN 07-10, 2014 CL Charlotte, NC SP Shock Soc C1 [Shinozaki, S.; Chang, K.; Sakai, M.; Shimizu, N.; Kaneki, M.] Harvard Univ, Sch Med, Shriners Hosp Children, Massachusetts Gen Hosp, Charlestown, MA USA. [Shinozaki, S.; Shimokado, K.] Tokyo Med & Dent Univ, Grad Sch, Dept Geriatr & Vasc Med, Tokyo, Japan. [Chang, K.] Univ Tokyo, Grad Sch Med, Tokyo, Japan. [Stamler, J.] Case Western Reserve Univ, Inst Transformat Mol Med, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2014 VL 41 SU 2 BP 22 EP 23 PG 2 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA AI6ET UT WOS:000336964600031 ER PT J AU Hafner, S Matallo, J Groger, M Wachter, U McCook, O Wood, M Whiteman, M Georgieff, M Calzia, E Radermacher, P Wepler, M AF Hafner, S. Matallo, J. Groeger, M. Wachter, U. McCook, O. Wood, M. Whiteman, M. Georgieff, M. Calzia, E. Radermacher, P. Wepler, M. TI EFFECTS OF THE SLOW-RELEASING SULFIDE DONOR GYY4137 DURING RESUSCITATED SEPTIC SHOCK IN ATHEROSCLEROTIC SWINE SO SHOCK LA English DT Meeting Abstract CT 37th Annual Conference of the Shock-Society on Shock CY JUN 07-10, 2014 CL Charlotte, NC SP Shock Soc C1 [Hafner, S.; Matallo, J.; Groeger, M.; Wachter, U.; McCook, O.; Georgieff, M.; Calzia, E.; Radermacher, P.; Wepler, M.] Univ Ulm Klinikum, Anasthesiol Klin, Sekt APV, Ulm, Germany. [Wood, M.] Univ Exeter, Coll Life & Environm Sci, Exeter, Devon, England. [Whiteman, M.] Univ Exeter, Sch Med, Exeter, Devon, England. [Wepler, M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RI Whiteman, Matthew/C-6079-2009 OI Whiteman, Matthew/0000-0002-6583-6779 NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2014 VL 41 SU 2 BP 53 EP 54 PG 2 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA AI6ET UT WOS:000336964600117 ER PT J AU Matallo, J Radermacher, P McCook, O Calzia, E Wepler, M Hafner, S AF Matallo, J. Radermacher, P. McCook, O. Calzia, E. Wepler, M. Hafner, S. TI CHARACTERIZATION OF LEFT VENTRICULAR FUNCTION DURING SEPTIC SHOCK IN ATHEROSCLEROTIC SWINE SO SHOCK LA English DT Meeting Abstract CT 37th Annual Conference of the Shock-Society on Shock CY JUN 07-10, 2014 CL Charlotte, NC SP Shock Soc C1 [Matallo, J.; Radermacher, P.; McCook, O.; Calzia, E.; Hafner, S.] Univ Ulm, D-89069 Ulm, Germany. [Wepler, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2014 VL 41 SU 2 BP 60 EP 60 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA AI6ET UT WOS:000336964600135 ER PT J AU Li, D Zou, L Feng, Y Gong, Y Cai, J Chao, W AF Li, D. Zou, L. Feng, Y. Gong, Y. Cai, J. Chao, W. TI TOLL-LIKE RECEPTORS UP-REGULATE COMPLEMENT FACTOR B VIA NF-kappa B PATHWAY IN HUMAN KIDNEY TUBULAR CELLS SO SHOCK LA English DT Meeting Abstract CT 37th Annual Conference of the Shock-Society on Shock CY JUN 07-10, 2014 CL Charlotte, NC SP Shock Soc C1 [Li, D.; Zou, L.; Feng, Y.; Gong, Y.; Cai, J.; Chao, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Li, D.] Xiangya 3rd Hosp, Changsha, Hunan, Peoples R China. 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 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2014 VL 41 SU 2 BP 71 EP 71 PG 1 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA AI6ET UT WOS:000336964600165 ER PT J AU Hafner, S Wepler, M Matallo, J Groger, M Wagner, K McCook, O Huber-Lang, M Dietl, P Georgieff, M Calzia, E Radermacher, P Wagner, F AF Hafner, S. Wepler, M. Matallo, J. Groeger, M. Wagner, K. McCook, O. Huber-Lang, M. Dietl, P. Georgieff, M. Calzia, E. Radermacher, P. Wagner, F. TI PHYSIOLOGICAL AND IMMUNE-BIOLOGICAL CHARACTERIZATION OF A LONG-TERM MURINE MODEL OF BLUNT CHEST TRAUMA SO SHOCK LA English DT Meeting Abstract CT 37th Annual Conference of the Shock-Society on Shock CY JUN 07-10, 2014 CL Charlotte, NC SP Shock Soc C1 [Hafner, S.; Wepler, M.; Matallo, J.; Groeger, M.; Wagner, K.; McCook, O.; Georgieff, M.; Calzia, E.; Radermacher, P.; Wagner, F.] Univ Ulm Klinikum, Anasthesiol Klin, Sekt APV, Ulm, Germany. [Wepler, M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Huber-Lang, M.] Univ Ulm Klinikum, Klin Unfall Hand Plast & Wiederherstellungschirur, Ulm, Germany. [Dietl, P.] Univ Ulm, Inst Allgemeine Physiol, D-89069 Ulm, Germany. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2014 VL 41 SU 2 BP 85 EP 86 PG 2 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA AI6ET UT WOS:000336964600208 ER PT J AU de Windt, TS Hendriks, JAA Zhao, X Vonk, LA Creemers, LB Dhert, WJA Randolph, MA Saris, DBF AF de Windt, Tommy S. Hendriks, Jeanine A. A. Zhao, Xing Vonk, Lucienne A. Creemers, Laura B. Dhert, Wouter J. A. Randolph, Mark A. Saris, Daniel B. F. TI Concise Review: Unraveling Stem Cell Cocultures in Regenerative Medicine: Which Cell Interactions Steer Cartilage Regeneration and How? SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Review DE Bone marrow stromal cells; Cellular therapy; Chondrogenesis; Clinical translation; Marrow stromal stem cells; Mesenchymal stem cells; Skeleton ID HUMAN ARTICULAR CHONDROCYTES; IMPROVED CHONDROGENIC DIFFERENTIATION; MESENCHYMAL STROMAL CELLS; QUALITY-OF-LIFE; IN-VITRO; TISSUE REGENERATION; FOLLOW-UP; OSTEOARTHRITIC CHONDROCYTES; MATURE CHONDROCYTES; BACK-PAIN AB Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both young, active patients and older patients disabled and affecting quality of life. In particular, cartilage injury not only imparts acute loss of function but also predisposes to OA. The increase in knowledge of the consequences of these diseases and the exponential growth in research of regenerative medicine have given rise to different treatment types. Of these, cell-based treatments are increasingly applied because they have the potential to regenerate cartilage, treat symptoms, and ultimately prevent or delay OA. Although these approaches give promising results, they require a costly in vitro cell culture procedure. The answer may lie in single-stage procedures that, by using cell combinations, render in vitro expansion redundant. In the last two decades, cocultures of cartilage cells and a variety of (mesenchymal) stem cells have shown promising results as different studies report cartilage regeneration in vitro and in vivo. However, there is considerable debate regarding the mechanisms and cellular interactions that lead to chondrogenesis in these models. This review, which included 52 papers, provides a systematic overview of the data presented in the literature and tries to elucidate the mechanisms that lead to chondrogenesis in stem cell cocultures with cartilage cells. It could serve as a basis for research groups and clinicians aiming at designing and implementing combined cellular technologies for single-stage cartilage repair and treatment or prevention of OA. C1 [de Windt, Tommy S.; Zhao, Xing; Vonk, Lucienne A.; Creemers, Laura B.; Dhert, Wouter J. A.; Saris, Daniel B. F.] Univ Med Ctr Utrecht, Dept Orthopaed, NL-3508 GA Utrecht, Netherlands. [Hendriks, Jeanine A. A.] CellCoTec, Bilthoven, Netherlands. [Zhao, Xing; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Lab Musculoskeletal Tissue Or, Boston, MA USA. [Zhao, Xing; Randolph, Mark A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. [Dhert, Wouter J. A.] Univ Utrecht, Fac Vet Med, Utrecht, Netherlands. [Saris, Daniel B. F.] Univ Twente, MIRA Inst Biotechnol & Tech Med, NL-7500 AE Enschede, Netherlands. RP Saris, DBF (reprint author), Univ Med Ctr Utrecht, Dept Orthopaed, POB 85500, NL-3508 GA Utrecht, Netherlands. EM d.saris@umcutrecht.nl OI Creemers, Laura/0000-0002-1585-3052 NR 76 TC 17 Z9 17 U1 3 U2 15 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 EI 2157-6580 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD JUN PY 2014 VL 3 IS 6 BP 723 EP 733 DI 10.5966/sctm.2013-0207 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA AI5WL UT WOS:000336940000018 PM 24763684 ER PT J AU Bockhorn, M Uzunoglu, FG Adham, M Imrie, C Milicevic, M Sandberg, AA Asbun, HJ Bassi, C Buchler, M Charnley, RM Conlon, K Cruz, LF Dervenis, C Fingerhutt, A Friess, H Gouma, DJ Hartwig, W Lillemoe, KD Montorsi, M Neoptolemos, JP Shrikhande, SV Takaori, K Traverso, W Vashist, YK Vollmer, C Yeo, CJ Izbicki, JR AF Bockhorn, Maximilian Uzunoglu, Faik G. Adham, Mustapha Imrie, Clem Milicevic, Miroslav Sandberg, Aken A. Asbun, Horacio J. Bassi, Claudio Buechler, Markus Charnley, Richard M. Conlon, Kevin Cruz, Laureano Fernandez Dervenis, Christos Fingerhutt, Abe Friess, Helmut Gouma, Dirk J. Hartwig, Werner Lillemoe, Keith D. Montorsi, Marco Neoptolemos, John P. Shrikhande, Shailesh V. Takaori, Kyoichi Traverso, William Vashist, Yogesh K. Vollmer, Charles Yeo, Charles J. Izbicki, Jakob R. CA Int Study Grp Pancreatic Surg TI Borderline resectable pancreatic cancer: A consensus statement by the International Study Group of Pancreatic Surgery (ISGPS) SO SURGERY LA English DT Article ID PORTAL-VEIN RESECTION; CELIAC AXIS RESECTION; MARGIN STATUS; VASCULAR RESECTION; DUCTAL ADENOCARCINOMA; DISTAL PANCREATECTOMY; PREOPERATIVE THERAPY; ARTERIAL RESECTION; SURVIVAL DURATION; BODY CANCER AB Background. This position statement was developed to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability. Methods. An international panel of pancreatic surgeons from well-established, high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer. Results. The International Study Group of Pancreatic Surgery (ISGPS) supports the National,Comprehensive Cancer Network criteria for the definition of BRPC. Current evidence supports operative exploration and resection, in the case of involvement of the mesentericoportal venous axis; in addition, a new classification of extrahepatic mesentericoportal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within I mm from the margin) used by the British Royal College of Pathologists. Standard preoperative diagnostics for BRPC may include: (I) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series; and also (2) the modified Glasgow Prognostic Score and the neutrophil/lymphocyte ratio because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers. Conclusion. Current evidence justifies portomesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given. C1 [Bockhorn, Maximilian; Uzunoglu, Faik G.; Vashist, Yogesh K.; Izbicki, Jakob R.] Univ Hosp Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, D-20246 Hamburg, Germany. [Adham, Mustapha] Hop Edouard Herriot, Dept HPB Surg, Lyon, France. [Imrie, Clem] Univ Glasgow, Acad Surg Unit, Glasgow, Lanark, Scotland. [Milicevic, Miroslav] Univ Belgrade, Clin Ctr Serbia, Surg Clin 1, Belgrade, Serbia. [Sandberg, Aken A.] Karolinska Univ Hosp, Karolinska Inst, Dept Surg, Stockholm, Sweden. [Asbun, Horacio J.] Mayo Clin, Dept Gen Surg, Jacksonville, FL 32224 USA. [Bassi, Claudio] Univ Verona, Pancreas Inst, Dept Surg & Oncol, I-37100 Verona, Italy. [Buechler, Markus; Hartwig, Werner] Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany. [Charnley, Richard M.] Freeman Rd Hosp, Dept HPB & Transplant Surg, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England. [Conlon, Kevin] Univ Dublin Trinity Coll, Professorial Surg Unit, Dublin 2, Ireland. [Cruz, Laureano Fernandez] Univ Barcelona, Hosp Clin Barcelona, Dept Surg, Barcelona, Spain. [Dervenis, Christos] Agia Olga Hosp, Dept Surg 1, Athens, Greece. [Fingerhutt, Abe] Ctr Hosp Intercommunal, Dept Digest Surg, Poissy, France. [Friess, Helmut] Tech Univ Munich, Klinikum Rechts Isar, Dept Surg, D-80290 Munich, Germany. [Gouma, Dirk J.] Univ Amsterdam, Acad Med Ctr, Dept Surg, NL-1105 AZ Amsterdam, Netherlands. [Lillemoe, Keith D.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Montorsi, Marco] Univ Milan, Inst Clin Humanitas IRCCS, Dept Gen Surg, Milan, Italy. [Neoptolemos, John P.] Univ Liverpool, Liverpool Canc Res UK Ctr, Dept Mol & Clin Canc Med, Liverpool L69 3BX, Merseyside, England. [Shrikhande, Shailesh V.] Tata Mem Hosp, Dept Gastrointestinal & HPB Surg Oncol, Bombay, Maharashtra, India. [Takaori, Kyoichi] Kyoto Univ, Grad Sch Med, Dept Surg, Kyoto, Japan. [Traverso, William] Ctr Pancreat & Liver Dis, St Lukes Clin, Boise, ID USA. [Vollmer, Charles] Hosp Univ Penn, Dept Gastrointestinal Surg, Philadelphia, PA 19104 USA. [Yeo, Charles J.] Thomas Jefferson Univ, Dept Surg, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA. RP Izbicki, JR (reprint author), Univ Hosp Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, Martinistr 52, D-20246 Hamburg, Germany. EM izbicki@uke.de RI Adham, Mustapha/A-1270-2017; OI Imrie, Clem/0000-0002-1190-7084 NR 75 TC 107 Z9 130 U1 7 U2 13 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 JUN PY 2014 VL 155 IS 6 BP 977 EP 988 DI 10.1016/j.surg.2014.02.001 PG 12 WC Surgery SC Surgery GA AI6RW UT WOS:000337005700003 PM 24856119 ER PT J AU Goldstein, S Bates, ER Bhatt, DL Cao, C Holmes, D Kupfer, S Martinez, F Spaeder, J Weitz, JI Ye, Z Zannad, F AF Goldstein, Sidney Bates, Eric R. Bhatt, Deepak L. Cao, Charlie Holmes, David Kupfer, Stuart Martinez, Felipe Spaeder, Jeffrey Weitz, Jeffrey I. Ye, Zhan Zannad, Faiez CA AXIOM Investigators TI Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients following acute coronary syndrome SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Oral factor Xa inhibitors; acute coronary syndrome; thrombosis ID MYOCARDIAL-INFARCTION; CONTROLLED TRIAL; DOUBLE-BLIND; ASPIRIN; WARFARIN; THROMBOSIS; METAANALYSIS; RIVAROXABAN; CLOPIDOGREL; THERAPY AB TAK-442 is an oral direct factor Xa inhibitor. We sought to determine the dose-dependent effect of TAK-442 on major bleeding when added to standard treatment in stabilised patients with acute coronary syndrome (ACS). In this phase II double-blind study, 2,753 ACS patients were randomised to TAK-442 or placebo in addition to usual care using a three-stage adaptive design. Patients were randomised to placebo in all stages, but doses of TAK-442 escalated from 10 mg BID, 20 mg twice-daily (BID), or 40 mg once-daily (QD) in stage 1; to 40 mg BID, 80 mg QD, or 80 mg BID in stage 2; and to 160 mg QD or 120 mg BID in stage 3. Study drug was started 36 hours after emergent treatment of ACS and within seven days of admission, and continued for 24 weeks. The primary endpoint was incidence of TIMI (thrombolysis in myocardial infarction) major bleeding. TIMI major bleeding incidence was low, but higher with the pooled TAK-442 doses than with placebo (17 [0.9%] vs 4 [0.5%]; p=0.47), although the difference was neither significant nor dose-dependent. However, a dose response was evident when using the modified ISTH scale. The incidence of cardiovascular events was similar among TAK-442 dose groups and placebo. When administered over a wide range of doses after an ACS event, TAK-442 treatment did not result in a dose-dependent increase in TIMI major bleeding, but increased bleeding was observed when a more sensitive bleeding scale was used. There was no evidence for efficacy. C1 [Goldstein, Sidney] Henry Ford Hosp, Div Cardiovasc Med, Detroit, MI 48202 USA. [Bates, Eric R.] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Cao, Charlie; Spaeder, Jeffrey; Ye, Zhan] Takeda Global Res & Dev Inc, Stat, Deerfield, IL USA. [Holmes, David] Mayo Clin, Dept Cardiovasc Dis, Rochester, MN USA. [Kupfer, Stuart] Takeda Global Res & Dev Ctr Inc, Clin Sci, Deerfield, IL USA. [Martinez, Felipe] Natl Univ Cordoba, Cordoba, Argentina. [Weitz, Jeffrey I.] McMaster Univ, Hamilton, ON, Canada. [Weitz, Jeffrey I.] Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada. [Zannad, Faiez] Henri Poincare Univ Nancy, Nancy, France. RP Goldstein, S (reprint author), 2799 W Grand Blvd, Detroit, MI 48202 USA. EM sgoldst1@hfhs.org RI Zadionchenko, Vladimir/A-7445-2016; Lotufo, Paulo/A-9843-2008 OI Zadionchenko, Vladimir/0000-0003-2377-5266; Lotufo, Paulo/0000-0002-4856-8450 FU Takeda Global Research & Development, Inc., Deerfield, IL, USA FX Research funding was provided by Takeda Global Research & Development, Inc., Deerfield, IL, USA. NR 21 TC 6 Z9 7 U1 1 U2 11 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 JUN PY 2014 VL 111 IS 6 BP 1141 EP 1152 DI 10.1160/TH13-07-0543 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA AI5CO UT WOS:000336883200016 PM 24671450 ER PT J AU Bang, JW Khalilzadeh, O Hamalainen, M Watanabe, T Sasaki, Y AF Bang, Ji Won Khalilzadeh, Omid Haemaelaeinen, Matti Watanabe, Takeo Sasaki, Yuka TI Location specific sleep spindle activity in the early visual areas and perceptual learning SO VISION RESEARCH LA English DT Article DE Visual perceptual learning; Consolidation; Sleep; Reactivation; Sleep spindle; Magnetoencephalography (MEG) ID DECLARATIVE MEMORY CONSOLIDATION; SURFACE-BASED ANALYSIS; SLOW-WAVE SLEEP; ORIENTATION DISCRIMINATION; MOTOR-SEQUENCE; TIME-COURSE; TOPOGRAPHIC DISTRIBUTION; TEXTURE-DISCRIMINATION; SYNAPTIC HOMEOSTASIS; DEPENDENT CHANGES AB Visual perceptual learning (VPL) is consolidated during sleep. However, the underlying neuronal mechanisms of consolidation are not yet fully understood. It has been suggested that the spontaneous brain oscillations that characterize sleep stages are indicative of the consolidation of learning and memory. We investigated whether sleep spindles and/or slow-waves are associated with consolidation of VPL during non-rapid eye movement (NREM) sleep during the first sleep cycle, using magnetoencephalography (MEG), magnetic resonance imaging (MRI), and polysomnography (PSG). We hypothesized that after training, early visual areas will show an increase in slow sigma, fast sigma and/or delta activity, corresponding to slow/fast sleep spindles and slow-waves, respectively. We found that during sleep stage 2, but not during slow-wave sleep, the slow sigma power within the trained region of early visual areas was larger after training compared to baseline, and that the increase was larger in the trained region than in the untrained region. However, neither fast sigma nor delta band power increased significantly after training in either sleep stage. Importantly, performance gains for the trained task were correlated with the difference of power increases in slow, sigma activity between the trained and untrained regions. This finding suggests that slow sigma activity plays a critical role in the consolidation of VPL, at least in sleep stage 2 during the first sleep cycle. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Bang, Ji Won; Watanabe, Takeo; Sasaki, Yuka] Brown Univ, Dept Cognit Linguist & Psychol Sci, Lab Cognit & Perceptual Learning, Providence, RI 02912 USA. [Haemaelaeinen, Matti] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Khalilzadeh, Omid] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Khalilzadeh, Omid] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sasaki, Y (reprint author), Brown Univ, Dept Cognit Linguist & Psychol Sci, BOX 1821,190 Thayer St, Providence, RI 02912 USA. EM ji_won_bang@brown.edu; o.khalilzadeh@gmail.com; msh@nmr.mgh.harvard.edu; takeo_watanabe@brown.edu; yuka_sasaki@brown.edu RI Hamalainen, Matti/C-8507-2013 FU NIH [R21EY018925, R01EY015980, R01EY019466, R01AG031941, R01MH091801, R01EB0009048]; NSF [BCS-1261765]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health; NIH Shared Instrumentation Grant Program; High-End Instrumentation Grant Program [S10RR014978, S10RR021110] FX This work was supported by grants from NIH (R21EY018925, R01EY015980, R01EY019466, R01AG031941, R01MH091801, R01EB0009048), and NSF (BCS-1261765). This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR014075, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and High-End Instrumentation Grant Program; specifically, grant numbers S10RR014978, and S10RR021110. We thank Daniel G. Wakeman for providing analysis tool, Erika Scilipoti for helping with data collection, Keiko Ogawa, and Masako Tamaki for scoring sleep stages, Jared Burgess for editing the manuscript. NR 103 TC 9 Z9 9 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 EI 1878-5646 J9 VISION RES JI Vision Res. PD JUN PY 2014 VL 99 SI SI BP 162 EP 171 DI 10.1016/j.visres.2013.12.014 PG 10 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA AI6UL UT WOS:000337012400019 PM 24380705 ER PT J AU Maeder, MMB Basnyat, B Harris, NS AF Maeder, Monika M. Brodmann Basnyat, Buddha Harris, N. Stuart TI From Matterhorn to Mt Everest: Empowering Rescuers and Improving Medical Care in Nepal SO WILDERNESS & ENVIRONMENTAL MEDICINE LA English DT Article DE wilderness medicine; emergency medicine; rescue work; public health AB This article describes a private initiative in which professional Swiss rescuers, based at the foot of the Matterhorn, trained Nepalese colleagues in advanced high altitude helicopter rescue and medical care techniques. What started as a limited program focused on mountain safety has rapidly developed into a comprehensive project to improve rescue and medical care in the Mt Everest area for both foreign travelers and the local Nepalese people. C1 [Maeder, Monika M. Brodmann] Univ Hosp Bern, Inselspital, Dept Emergency Med, CH-3010 Bern, Switzerland. [Basnyat, Buddha] Nepal Int Clin, Kathmandu, Nepal. [Harris, N. Stuart] Massachusetts Gen Hosp, Dept Emergency Med, Div Wilderness Med, Boston, MA 02114 USA. RP Maeder, MMB (reprint author), Univ Hosp Bern, Inselspital, Dept Emergency Med, CH-3010 Bern, Switzerland. EM monika.brodmannmaeder@insel.ch FU Alpine Rescue Foundation Zermatt; Nicole Niquille Foundation FX Financial support was given by Alpine Rescue Foundation Zermatt by paying wages, travel expenses, and lodging during the instructors' stay in Nepal. Nicole Niquille Foundation paid the medical instructor's travel expenses and lodging during her instruction for the staff of Pasang Lhamu Nicole Niquille Hospital in Lukla, Nepal. NR 3 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1080-6032 EI 1545-1534 J9 WILD ENVIRON MED JI Wildern. Environ. Med. PD SUM PY 2014 VL 25 IS 2 BP 177 EP 181 PG 5 WC Public, Environmental & Occupational Health; Sport Sciences SC Public, Environmental & Occupational Health; Sport Sciences GA AI5YL UT WOS:000336946800007 PM 24864066 ER PT J AU Lee, AM Engel, LC Hui, GC Liew, G Ferencik, M Sidhu, MS Hoffmann, U Ghoshhajra, BB AF Lee, Ashley M. Engel, Leif-Christopher Hui, Gladwin C. Liew, Gary Ferencik, Maros Sidhu, Manavjot S. Hoffmann, Udo Ghoshhajra, Brian B. TI Coronary computed tomography angiography at 140 kV versus 120 kV: assessment of image quality and radiation exposure in overweight and moderately obese patients SO ACTA RADIOLOGICA LA English DT Article DE Cardiac; CT; CT angiography; adult; dosimetry; radiation safety ID TUBE POTENTIAL SELECTION; BODY-MASS INDEX; DUAL-SOURCE CT; DIAGNOSTIC-ACCURACY; ASSOCIATION; ATTENUATION; PROTOCOL; ADULTS; NOISE AB Background: Although a tube potential of 140 kV is available on most computed tomography (CT) scanners, its incremental diagnostic value versus 120 kV has been controversial. Purpose: To retrospectively evaluate the image quality and radiation exposure of cardiac computed tomography angiography (CCTA) performed at 140 kV in comparison to CCTA at 120 kV in overweight and moderately obese patients. Material and Methods: Eighty-eight patients who were referred for CCTA between January 2010 and May 2012 were included. Forty-four patients who were overweight or moderately obese (body mass index [BMI], 25-35 kg/m(2)) underwent CCTA with dual-source CT (DSCT) scanner at 140 kV. Forty-four match controls who underwent CCTA with DSCT at 120 kV were identified per BMI, average heart rate, scan indication, and scan acquisition mode. All scans were performed per routine protocols with direct physician supervision. Quantitative image metrics (CT attenuation, image noise, contrast-to-noise ratio [CNR], and signal-to-noise ratio [SNR] of left main [LM] and proximal right coronary artery [RCA]) were assessed. Effective radiation dose was compared between the two groups. Results: Overall, all scans were diagnostic without any non-evaluable coronary segment per clinical report. 140 kV had a lower attenuation and image noise versus 120 kV (P<0.01). Both SNR and CNR of proximal coronary arteries were similar between 140 kV and 120 kV (SNR, LM P = 0.93, RCA P = 0.62; CNR, LM P = 0.57, RCA P = 0.77). 140 kV was associated with a 35.3% increase in effective radiation dose as compared with 120 kV (5.1 [3.6-8.2] vs. 3.3 [2.0-5.1] mSv, respectively; P<0.01). Conclusion: 140 kV CCTA resulted in similar image quality but a higher effective radiation dose in comparison to 120 kV CCTA. Therefore, in overweight and moderately obese patients, a tube potential of 120 kV may be sufficient for CCTA with diagnostic image quality. C1 [Lee, Ashley M.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Div Cardiol, Boston, MA USA. RP Lee, AM (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM amshlee@hotmail.com NR 24 TC 3 Z9 4 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0284-1851 EI 1600-0455 J9 ACTA RADIOL JI Acta Radiol. PD JUN PY 2014 VL 55 IS 5 BP 554 EP 562 DI 10.1177/0284185113502745 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI3XM UT WOS:000336799000005 PM 24031049 ER PT J AU Kratz, M Marcovina, S Nelson, JE Yeh, MM Kowdley, KV Callahan, HS Song, XL Di, CZ Utzschneider, KM AF Kratz, Mario Marcovina, Santica Nelson, James E. Yeh, Matthew M. Kowdley, Kris V. Callahan, Holly S. Song, Xiaoling Di, Chongzhi Utzschneider, Kristina M. TI Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not beta-cell function in humans SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID TRANS-PALMITOLEIC ACID; ADIPOSE-TISSUE; PLASMA; VALIDATION; BIOMARKERS; RESISTANCE; ADULTS; RISK AB Background: Plasma phospholipid concentrations of trans-palmitoleic acid (trans-16: ln-7), a biomarker of dairy fat intake, are inversely associated with incident type 2 diabetes in 2 US cohorts. Objective: The objective was to investigate whether the intake of trans-16: ln-7 in particular, or dairy fat in general, is associated with glucose tolerance and key factors determining glucose tolerance. Design: A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index (BMI)- and age-matched controls. The concentrations of trans-16:1n 7 and 2 other biomarkers of dairy fat intake, 15:0 and 17:0, were measured in plasma phospholipids and free fatty acids (FFAs). Liver fat was estimated by computed tomography derived liver-spleen ratio. Intravenous-glucose-tolerance tests and oralglucose-tolerance test (OGTT) and hyperinsulinemic-euglycemic clamps were performed to assess beta-cell function and hepatic and systemic insulin sensitivity. Results: In multivariate analyses adjusted for age, sex, and BMI, phospholipid 17:0, phospholipid trans-16:1n-7, PIA 15:0, and FFA 17:0 were inversely associated with fasting plasma glucose, the area under the curve for glucose during an OGTT, and liver fat. Phospholipid trans-16:1n 7 was also positively associated with hepatic and systemic insulin sensitivity. None of the biomarkers were associated with beta-cell function. The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat, but strengthened by adjusting for beta-cell function. Conclusion: Although we cannot rule out reverse causation, these data support the hypothesis that dairy fat improves glucose tolerance, possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat. This trial was registered at clinicaltrials.gov as NCT01289639. C1 [Kratz, Mario; Song, Xiaoling] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, Seattle, WA 98109 USA. [Di, Chongzhi] Biostat Program, Seattle, WA 98109 USA. [Kratz, Mario; Utzschneider, Kristina M.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Kratz, Mario] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Yeh, Matthew M.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Marcovina, Santica] Univ Washington, Northwest Lipid Res Labs, Seattle, WA 98195 USA. [Nelson, James E.; Kowdley, Kris V.] Virginia Mason Med Ctr, Benaroya Res Inst, Seattle, WA 98101 USA. [Callahan, Holly S.] Univ Washington, Inst Translat Hlth Sci, Seattle, WA 98195 USA. [Utzschneider, Kristina M.] VA Puget Sound Hlth Care Syst, Dept Med, Div Endocrinol, Seattle, WA USA. RP Kratz, M (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Mail Stop M4-B402,1100 Fairview Ave North, Seattle, WA 98109 USA. EM mkratz@fhcrc.org FU US Department of Veterans Affairs, Office of Research and Development Medical Research Service; NIH [UL1RR025014, P30DK017047, P30DK035816, DK020579, RR000954, DK056341, T32DK007247, U01DK061728, K24DK002957, R21ES022332] FX Supported by the US Department of Veterans Affairs, Office of Research and Development Medical Research Service, and NIH grant nos. UL1RR025014, P30DK017047, P30DK035816, DK020579, RR000954, DK056341, T32DK007247, U01DK061728, K24DK002957, and R21ES022332. NR 20 TC 17 Z9 17 U1 1 U2 15 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 JUN PY 2014 VL 99 IS 6 BP 1385 EP 1396 DI 10.3945/ajcn.113.075457 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AH9NW UT WOS:000336470100011 PM 24740208 ER PT J AU Kim, HT Frederick, D Armand, P Andler, E Kao, G Cutler, C Koreth, J Alyea, EP Antin, JH Soiffer, RJ Ritz, J Ho, VT AF Kim, Haesook T. Frederick, David Armand, Philippe Andler, Emily Kao, Grace Cutler, Corey Koreth, John Alyea, Edwin P., III Antin, Joseph H. Soiffer, Robert J. Ritz, Jerome Ho, Vincent T. TI White blood cell recovery after allogeneic hematopoietic cell transplantation predicts clinical outcome SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID VERSUS-HOST-DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; LYMPHOCYTE RECOVERY; MONOCYTE RECOVERY; BONE-MARROW; MALIGNANCIES; SURVIVAL; IMPACT; RISK; SCT AB To determine whether outcome after allogeneic hematopoietic cell transplantation (HCT) could be estimated by using peripheral white blood cell count (WBC) as a metric that integrates several aspects of HCT recovery, we conducted a retrospective study of 1,109 adult patients who underwent first allogeneic HCT from 2003 through 2009. WBC at 1-3 months after HCT was categorized as low (<2), normal (2-10), and high (>10 x 10(9) cells/L). Overall survival (OS) and progression-free survival (PFS) were lower for patients with low or high WBC at 1-3 months after HCT (P<0.0001). We developed a predictive three-group risk model based on the pattern of WBC recovery early after HCT. Five-year OS was 47, 30, and 15% (P<0.0001) and 5-year PFS was 39, 22, and 14% for patients in the three different risk groups (P<0.0001). The pattern of WBC recovery early after HCT provides prognostic information for relapse, nonrelapse mortality, progression-free survival, and overall survival. A scoring system based on the trajectory of the WBC in the first 3 months after HCT can effectively stratify patients into three groups with different PFS and OS. If validated, this system could be useful in the clinical management of patients after HCT, and to stratify patients enrolled on HCT clinical trials. Am. J. Hematol. 89:591-597, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Frederick, David; Armand, Philippe; Andler, Emily; Kao, Grace; Cutler, Corey; Koreth, John; Alyea, Edwin P., III; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome; Ho, Vincent T.] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02215 USA. RP Kim, HT (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA. EM htkimc@jimmy.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [P01 CA142106, P01 CA018029] NR 16 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 BP 591 EP 597 DI 10.1002/ajh.23695 PG 7 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600207 PM 24549932 ER PT J AU Black, L Selby, R Hoffman, S Chen, D Meijer, P Plumhoff, E Van Cott, E AF Black, Lesley Selby, Rita Hoffman, Suzanne Chen, Dong Meijer, Piet Plumhoff, Elizabeth Van Cott, Elizabeth TI ANTI-XA ASSAYS FOR UNFRACTIONATED HEPARIN (UFH) AND LOW MOLECULAR WEIGHT HEPARIN (LMWH): ANALYSIS OF THE QUALITY OF PERFORMANCE BY NORTH AMERICAN LABORATORIES SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Black, Lesley; Selby, Rita] Univ Toronto, Lab Med Program, Univ Hlth Network, Toronto, ON, Canada. [Selby, Rita] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Clin Pathol, Toronto, ON, Canada. [Hoffman, Suzanne] Univ Wisconsin, Madison, WI USA. [Chen, Dong; Plumhoff, Elizabeth] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands. [Van Cott, Elizabeth] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 124 BP E60 EP E60 PG 1 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600122 ER PT J AU Chen, D Selby, R Meijer, P Plumhoff, EA Van Cott, EM AF Chen, Dong Selby, Rita Meijer, Piet Plumhoff, Elizabeth A. Van Cott, Elizabeth M. TI ANTITHROMBIN ACTIVITY AND ANTIGEN ASSAYS: AN ANALYSIS OF LABORATORY PERFORMANCE SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Chen, Dong; Plumhoff, Elizabeth A.] Mayo Clin, Rochester, MN USA. [Selby, Rita] Univ Toronto, Toronto, ON, Canada. [Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 48 BP E23 EP E23 PG 1 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600047 ER PT J AU Grabowski, EF Paidas, MJ Buonanno, FS Thibert, RL Musolino, PL Pels, S Ment, L Triche, E Caruso, PA Roberts, DJ Sze, G Van Cott, EM Murphy, S Krishnamoorthy, KS AF Grabowski, Eric F. Paidas, Michael J. Buonanno, Ferdinando S. Thibert, Ronald L. Musolino, Patricia L. Pels, Sally Ment, Laura Triche, Elizabeth Caruso, Paul A. Roberts, Drucilla J. Sze, Gordon Van Cott, Elizabeth M. Murphy, Sarah Krishnamoorthy, Kalpathy S. TI PREDICTING LATE AND EARLY PERINATAL STROKE IN HIGH-RISK PREGNANCIES AND HIGH-RISK NEONATES SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Grabowski, Eric F.; Buonanno, Ferdinando S.; Thibert, Ronald L.; Musolino, Patricia L.; Caruso, Paul A.; Roberts, Drucilla J.; Van Cott, Elizabeth M.; Murphy, Sarah; Krishnamoorthy, Kalpathy S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Paidas, Michael J.; Pels, Sally; Ment, Laura; Sze, Gordon] Yale Univ, Sch Med, New Haven, CT USA. [Triche, Elizabeth] Brown Univ, Providence, RI 02912 USA. RI Triche, Elizabeth/I-4986-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 113 BP E55 EP E55 PG 1 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600111 ER PT J AU Hsu, PH Marlar, RA Zantek, ND Smock, KJ Plumhoff, EA Meijer, P Van Cott, EM AF Hsu, Peihong Marlar, Richard A. Zantek, Nicole D. Smock, Kristi J. Plumhoff, Elizabeth A. Meijer, Piet Van Cott, Elizabeth M. TI ACTIVATED PROTEIN C RESISTANCE TESTING: ASSESSMENT OF THE QUALITY OF TESTING PERFORMED BY NORTH AMERICAN SPECIALIZED COAGULATION LABORATORIES SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Hsu, Peihong] Hofstra North Shore Long Isl Jewish Sch Med, Dept Pathol & Lab Med, Lake Success, NY USA. [Marlar, Richard A.] Univ Oklahoma, Dept Pathol, Hlth Sci Ctr, Tulsa, OK USA. [Zantek, Nicole D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Smock, Kristi J.] Univ Utah, Dept Pathol, ARUP Labs, Salt Lake City, UT USA. [Plumhoff, Elizabeth A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 80 BP E38 EP E38 PG 1 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600078 ER PT J AU Marshall, A Campigotto, F Neuberg, D Rowe, B Connors, J AF Marshall, Ariela Campigotto, Federico Neuberg, Donna Rowe, Betty Connors, Jean TI RATES OF RECURRENT VENOUS THROMBOEMBOLISM AMONGST ONCOLOGY PATIENTS MANAGED IN A DEDICATED ANTICOAGULATION CLINIC NOT HIGHER WITH WARFARIN COMPARED TO PARENTERAL ANTICOAGULANTS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Marshall, Ariela; Campigotto, Federico; Neuberg, Donna; Rowe, Betty; Connors, Jean] Dana Farber Canc Inst, Boston, MA 02115 USA. [Marshall, Ariela] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rowe, Betty; Connors, Jean] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 138 BP E66 EP E66 PG 1 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600135 ER PT J AU Marshall, A Drucker, A Dzik, WH AF Marshall, Ariela Drucker, Adrienne Dzik, Walter H. TI USE OF AMINOCAPROIC ACID IN PATIENTS WITH HEMATOLOGIC MALIGNANCY: A CASE SERIES FROM THE MASSACHUSETTS GENERAL HOSPITAL SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Marshall, Ariela] Dana Farber Canc Inst, Boston, MA 02115 USA. [Marshall, Ariela; Drucker, Adrienne; Dzik, Walter H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 91 BP E43 EP E44 PG 2 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600089 ER PT J AU Milling, TJ Refaai, MA Sarode, R Lewis, B Mangione, A Durn, BL Goldstein, JN AF Milling, Truman J. Refaai, Majed A. Sarode, Ravi Lewis, Brandon Mangione, Antoinette Durn, Billie L. Goldstein, Joshua N. TI SAFETY OF A 4-FACTOR PROTHROMBIN COMPLEX CONCENTRATE (4F-PCC) VERSUS PLASMA FOR VITAMIN K ANTAGONIST REVERSAL: AN INTEGRATED DATA ANALYSIS OF TWO PHASE III CLINICAL TRIALS SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Milling, Truman J.] Univ Med Ctr Brackenridge, Seton UT Southwestern Clin Res Inst Austin, Dell Childrens Med Ctr, Austin, TX USA. [Refaai, Majed A.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Sarode, Ravi] UT Southwestern Med Ctr, Dallas, TX USA. [Lewis, Brandon] Texas A&M Hlth Sci Ctr, St Joseph Reg Hlth Ctr, College Stn, TX USA. [Mangione, Antoinette; Durn, Billie L.] CSL Behring, King Of Prussia, PA USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 54 BP E26 EP E26 PG 1 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600053 ER PT J AU Pruthi, RK Plumhoff, EA Nichols, WL Meijer, P Van Cott, EM AF Pruthi, Rajiv K. Plumhoff, Elizabeth A. Nichols, William L. Meijer, Piet Van Cott, Elizabeth M. TI QUALITY OF FACTOR VIII INHIBITOR TESTING IN NORTH AMERICAN SPECIALIZED COAGULATION LABORATORIES SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Pruthi, Rajiv K.; Plumhoff, Elizabeth A.; Nichols, William L.] Mayo Clin, Rochester, MN USA. [Meijer, Piet] ECAT Fdn Netherlands, Leiden, Netherlands. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 57 BP E27 EP E27 PG 1 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600055 ER PT J AU Smock, KJ Plumhoff, EA Meijer, P Hsu, PH Zantek, ND Heikal, NM Van Cott, EM AF Smock, Kristi J. Plumhoff, Elizabeth A. Meijer, Piet Hsu, Peihong Zantek, Nicole D. Heikal, Nahla M. Van Cott, Elizabeth M. TI PROTEIN S: QUALITY OF TESTING IN NORTH AMERICAN SPECIALIZED COAGULATION LABORATORIES SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Smock, Kristi J.; Heikal, Nahla M.] Univ Utah, Dept Pathol, ARUP Labs, Salt Lake City, UT USA. [Plumhoff, Elizabeth A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands. [Hsu, Peihong] Hofstra North Shore Long Isl Jewish Sch Med, Dept Pathol & Lab Med, Lake Success, NY USA. [Zantek, Nicole D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 62 BP E29 EP E30 PG 2 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600060 ER PT J AU Zantek, ND Hsu, PH Meijer, P Plumhoff, EA Refaai, MA Smock, KJ Van Cott, EM AF Zantek, Nicole D. Hsu, Peihong Meijer, Piet Plumhoff, Elizabeth A. Refaai, Majed A. Smock, Kristi J. Van Cott, Elizabeth M. TI QUALITY OF FACTOR XI ACTIVITY TESTING IN NORTH AMERICAN SPECIALIZED COAGULATION LABORATORIES SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Zantek, Nicole D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Hsu, Peihong] Hofstra North Shore Long Isl Jewish Sch Med, Dept Pathol Lab Med, Lake Success, NY USA. [Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands. [Plumhoff, Elizabeth A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Refaai, Majed A.] Univ Rochester, Sch Med & Dent, Dept Pathol & Lab Med, Rochester, NY USA. [Smock, Kristi J.] Univ Utah, Dept Pathol, ARUP Labs, Salt Lake City, UT USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JUN PY 2014 VL 89 IS 6 MA 66 BP E31 EP E31 PG 1 WC Hematology SC Hematology GA AI1NU UT WOS:000336618600064 ER PT J AU Turner, AP Williams, RM Norvell, DC Henderson, AW Hakimi, KN Blake, DJ Czerniecki, JM AF Turner, Aaron P. Williams, Rhonda M. Norvell, Daniel C. Henderson, Alison W. Hakimi, Kevin N. Blake, Donna Jo Czerniecki, Joseph M. TI Prevalence and 1-Year Course of Alcohol Misuse and Smoking in Persons with Lower Extremity Amputation as a Result of Peripheral Arterial Disease SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Smoking; Alcohol Misuse; Amputation; Prevalence; Social Support ID SPINAL-CORD-INJURY; DISORDERS IDENTIFICATION TEST; TYPE-2 DIABETES-MELLITUS; LOWER-LIMB AMPUTATION; 6.5-YEAR FOLLOW-UP; RISK-FACTORS; SOCIAL SUPPORT; MULTIPLE-SCLEROSIS; CIGARETTE-SMOKING; UNITED-STATES AB Objective The aim of this study was to describe prevalence of alcohol misuse and smoking among individuals with amputations as a result of peripheral arterial disease before surgery and 12 mos after surgery, changes in these behaviors over time, and factors associated with change. Design This is a prospective cohort study of 75 veterans experiencing their first major unilateral amputation. Measures included demographic and general health information, Alcohol Use Disorders Identification Test, smoking behaviors, and social support. Results Sixteen percent of the participants reported engaging in alcohol misuse at presurgical baseline; and 13% at 12 mos after amputation. Thirty-seven percent of the participants were categorized as smokers at baseline; this number dropped to 29% at 12 mos after amputation. Among those who decreased drinking and quit smoking, there was a trend indicating greater social support. Conclusions The participants endorsed drinking and smoking behaviors at levels consistent with other types of disability and with veterans using the Veterans Health Administration for their health care. Even with a variety of health concerns, after amputation, most of the smokers and those engaging in alcohol misuse continued to smoke and drink at their preamputation rate. The presence of social support may encourage health behavior change and is an important area for future research and intervention. C1 [Turner, Aaron P.; Williams, Rhonda M.; Henderson, Alison W.; Hakimi, Kevin N.; Czerniecki, Joseph M.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Turner, Aaron P.; Williams, Rhonda M.; Hakimi, Kevin N.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Norvell, Daniel C.] Spectrum Res Inc, Tacoma, WA USA. [Blake, Donna Jo] Denver VAMC, Denver, CO USA. [Blake, Donna Jo] Univ Colorado, Denver, CO 80202 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, RCS 117,1660 S Columbian Way, Seattle, WA 98108 USA. OI Turner, Aaron/0000-0001-6897-8003 FU United States Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development [A41241, B4927W] FX Supported by the United States Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development (Merit Review A41241, Joseph M. Czerniecki, PI, and Career Development Award B4927W, Aaron P. Turner, PI). NR 78 TC 1 Z9 1 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JUN PY 2014 VL 93 IS 6 BP 493 EP 502 DI 10.1097/PHM.0000000000000055 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AI3FC UT WOS:000336744900005 PM 24508927 ER PT J AU Lee, JXW Yusin, JS Randhawa, I AF Lee, Joyce Xiang Wu Yusin, Joseph Stephen Randhawa, Inderpal TI Properdin deficiency-associated bronchiectasis SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter C1 [Lee, Joyce Xiang Wu; Yusin, Joseph Stephen] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Allergy & Immunol, Los Angeles, CA 90073 USA. [Randhawa, Inderpal] Long Beach Mem Med Ctr, Long Beach, CA USA. RP Lee, JXW (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Allergy & Immunol, Los Angeles, CA 90073 USA. EM joycexianglee@gmail.com NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD JUN PY 2014 VL 112 IS 6 BP 557 EP 559 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA AH9XJ UT WOS:000336498400017 PM 24793003 ER PT J AU Carbone, LD Chin, AS Lee, TA Burns, SP Svircev, JN Hoenig, HM Bailey, L Weaver, FM AF Carbone, Laura D. Chin, Amy S. Lee, Todd A. Burns, Stephen P. Svircev, Jelena N. Hoenig, Helen M. Bailey, Lauren Weaver, Frances M. TI Thiazide Use Is Associated With Reduced Risk for Incident Lower Extremity Fractures in Men With Spinal Cord Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Fractures, bone; Men; Rehabilitation; Spinal cord injuries; Thiazides ID BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; HIP FRACTURE; OLDER-ADULTS; DIURETIC USE; VITAMIN-D; OSTEOPOROSIS; WORLDWIDE; VETERANS AB Objective: To determine the association between thiazide use and lower extremity fractures in patients who are men with a spinal cord injury (SCI). Design: Cohort study from fiscal years 2002 to 2007. Setting: Medical centers. Participants: Men (N=6969) with an SCI from the Veterans Affairs (VA) Spinal Cord Dysfunction (SCD) Registry, including 1433 users of thiazides and 5536 nonusers of thiazides. Intervention: Thiazide use versus nonuse. Main Outcome Measure: Incident lower extremity fractures. Results: Among the men, 21% in the VA SCD Registry (fiscal years 2002-2007) included in these analyses used thiazide diuretics. There were 832 incident lower extremity fractures over the time period of this study: 110 fractures (7.7%) in 1433 thiazide users and 722 fractures (13%) in 5536 nonusers of thiazides. In unadjusted and adjusted models alike, thiazide use was associated with at least a one-quarter risk reduction in lower extremity fracture at any given point in time (unadjusted: hazard ratio (HR)=.75; 95% confidence interval (CI), .59-.94; adjusted: HR=.74; 95% CI, .58-.95). Conclusions: Thiazide use is common in men with SCI and is associated with a decreased likelihood for lower extremity fractures. (C) 2014 by the American Congress of Rehabilitation Medicine C1 [Carbone, Laura D.] Charlie Norwood Vet Affairs Med Ctr, Augusta, GA USA. [Carbone, Laura D.] Georgia Regents Univ, Dept Med, Augusta, GA 30912 USA. [Chin, Amy S.; Lee, Todd A.; Bailey, Lauren; Weaver, Frances M.] Care of Hines EJ, Jr Vet Affairs Hosp, Hines, IL USA. [Lee, Todd A.; Bailey, Lauren] Univ Illinois, Chicago, IL USA. [Burns, Stephen P.; Svircev, Jelena N.] Vet Affairs Puget Sound, Spinal Cord Injury Serv, Seattle, WA USA. [Burns, Stephen P.; Svircev, Jelena N.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hoenig, Helen M.] Durham Vet Affairs Med Ctr, Durham, NC USA. [Weaver, Frances M.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. RP Carbone, LD (reprint author), Georgia Regents Univ, Dept Med, Sect Rheumatol & Immunol, 1120 15th St,BI 5086, Augusta, GA 30912 USA. EM lcarbone@gru.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development [UR 08-033] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (grant no. UR 08-033). NR 38 TC 2 Z9 2 U1 2 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 2014 VL 95 IS 6 BP 1015 EP 1020 DI 10.1016/j.apmr.2013.12.013 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AI3OY UT WOS:000336773000002 PM 24378805 ER PT J AU Sullivan-Singh, SJ Sawyer, K Ehde, DM Bell, KR Temkin, N Dikmen, S Williams, RM Hoffman, JM AF Sullivan-Singh, Sarah J. Sawyer, Kathryn Ehde, Dawn M. Bell, Kathleen R. Temkin, Nancy Dikmen, Sureyya Williams, Rhonda M. Hoffman, Jeanne M. TI Comorbidity of Pain and Depression Among Persons With Traumatic Brain Injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Brain injuries; Depression; Pain; Rehabilitation ID CUT-POINTS; SEVERITY; DISORDERS; PREVALENCE; VALIDITY; OUTCOMES AB Objective: To assess the prevalence of pain, depression, and comorbid pain and depression among a civilian sample of persons with traumatic brain injury (TBI). Design: Longitudinal survey design with 1-year follow-up. Setting: Inpatient rehabilitation and the community. Participants: Participants (N = 158) admitted to inpatient rehabilitation after moderate to severe TBI. Interventions: Not applicable. Main Outcome Measures: Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9); pain was assessed with a numerical rating scale from 0 (no pain) to 10 (worst pain). Participants who reported average pain >= 4 were classified as having pain, and participants with PHQ-9 scores >= 10 were classified as depressed. Results: Both pain and depression were more prevalent at baseline assessment (pain: 70%; depression: 31%) than at year 1 (pain: 34%; depression: 22%). Comorbid pain and depression declined from 27% at baseline to 18% at year 1. Pain was significantly associated with depression at baseline (relative risk: 2.62, P = .003) and at year 1 (relative risk: 7.98, P<.001). Conclusions: Pain and depression are common and frequently co-occur in persons with TBI. Although their frequency declined over the first year after injury, the strength of their association increased. Assessment and treatment of both conditions simultaneously may lead to improved outcomes, both early after TBI and over time. (C) 2014 by the American Congress of Rehabilitation Medicine C1 [Sullivan-Singh, Sarah J.; Sawyer, Kathryn; Ehde, Dawn M.; Bell, Kathleen R.; Temkin, Nancy; Dikmen, Sureyya; Williams, Rhonda M.; Hoffman, Jeanne M.] Univ Washington, Dept Rehabil Med, Sch Med, Seattle, WA 98104 USA. [Temkin, Nancy; Dikmen, Sureyya] Univ Washington, Dept Neurol Surg, Sch Med, Seattle, WA 98104 USA. [Temkin, Nancy] Univ Washington, Dept Biostat, Sch Med, Seattle, WA 98104 USA. [Dikmen, Sureyya] Univ Washington, Dept Psychiat & Biobehav Sci, Sch Med, Seattle, WA 98104 USA. [Williams, Rhonda M.] Vet Affairs Puget Sound Healthcare Syst, Rehabil Care Serv, Seattle, WA USA. RP Sullivan-Singh, SJ (reprint author), Univ Washington, Dept Rehabil Med, Harborview Med Ctr, 325 Ninth Ave,Box 359612, Seattle, WA 98104 USA. EM sarahsullivansingh@gmail.com FU National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems [H133A070032]; Department of Defense Congressionally Directed Medical Research Programs [W81XWH-12-2-0109] FX Supported by the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems (grant no. H133A070032) and Department of Defense Congressionally Directed Medical Research Programs (grant no. W81XWH-12-2-0109). NR 27 TC 10 Z9 10 U1 1 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 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUN PY 2014 VL 95 IS 6 BP 1100 EP 1105 DI 10.1016/j.apmr.2014.02.001 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA AI3OY UT WOS:000336773000014 PM 24561058 ER PT J AU Spector, M Ying, JYR AF Spector, Myron Ying, Jackie Yi-Ru TI An interview with Jackie Yi-Ru Ying: the compleat multi-tasker SO BIOMEDICAL MATERIALS LA English DT Editorial Material ID FIBERS C1 [Spector, Myron] Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. [Ying, Jackie Yi-Ru] ASTAR, IBN, Singapore, Singapore. [Ying, Jackie Yi-Ru] Inst New Mat, Saarbrucken, Germany. [Ying, Jackie Yi-Ru] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Spector, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 EI 1748-605X J9 BIOMED MATER JI Biomed. Mater. PD JUN PY 2014 VL 9 IS 3 AR 030401 DI 10.1088/1748-6041/9/3/030401 PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AI3DA UT WOS:000336738000001 ER PT J AU Violant, D Galofre, M Nart, J Teles, RP AF Violant, Deborah Galofre, Marta Nart, Jose Teles, Ricardo Patricio TI In vitro evaluation of a multispecies oral biofilm on different implant surfaces SO BIOMEDICAL MATERIALS LA English DT Article DE checkerboard DNA-DNA hybridization; implant surface; oral biofilm; periimplantitis ID DENTAL IMPLANTS; BACTERIAL-COLONIZATION; TITANIUM IMPLANTS; FOLLOW-UP; PLAQUE; VIVO; HYDROXYAPATITE; EPIDERMIDIS; VALIDATION; OSTEOBLAST AB Biofilm accumulation on implant surfaces is one of the most important factors for early and late implant failure. Because of the related clinical implications, the aim of this in vitro study was to compare the bacterial cell attachment of a four-species oral biofilm on titanium discs of purity grade 2 and 4, with machined surfaces and etched-thermochemically modified with Avantblast (R). The in vitro biofilm model was composed of early (Actinomyces naeslundii, Streptococcus gordonii), secondary (Veillonella parvula), and intermediate (Fusobacterium nucleatum ssp. polymorphum) colonizers of tooth surfaces. A total of 36 discs were divided into four groups: Tigr2-c (titanium grade 2, machined surface), Tigr2-t (titanium grade 2, modified surface with Avantblast (R)), Tigr4-c (titanium grade 4, machined surface), Tigr4-t (titanium grade 4, modified surface with Avantblast (R)). The experiment was repeated three times. Biofilm viability was tested with 1% 2, 3, 5-triphenyltetrazolium chloride solution and bacterial cell quantification by checkerboard DNA-DNA hybridization. Descriptive analysis was performed to evaluate biofilm composition and differences between groups were checked with the Mann-Whitney test (p < 0.05). After one week, multispecies biofilms showed a similar pattern of bacterial composition on all analyzed implant surfaces. The most prevalent bacterium was V. parvula (similar to 50% of the total biomass), followed by S. gordonii (similar to 30%), F. nucleatum ssp. polymorphum (similar to 10%) and A. naeslundii (<5%). Total bacterial biomass was significantly higher in both grade-4-titanium surfaces (p < 0.05). The results demonstrated that not only implant surface treatment, but also titanium purity, influence early bacterial colonization. C1 [Violant, Deborah; Galofre, Marta; Nart, Jose] Univ Int Catalunya, Dept Periodont, Barcelona 08195, Spain. [Violant, Deborah; Teles, Ricardo Patricio] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 USA. RP Violant, D (reprint author), Univ Int Catalunya, Dept Periodont, Josep Trueta S-N, Barcelona 08195, Spain. EM dviolant@uic.es OI Violant, Deborah/0000-0002-3292-270X NR 54 TC 5 Z9 5 U1 2 U2 18 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1748-6041 EI 1748-605X J9 BIOMED MATER JI Biomed. Mater. PD JUN PY 2014 VL 9 IS 3 AR 035007 DI 10.1088/1748-6041/9/3/035007 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AI3DA UT WOS:000336738000008 PM 24770899 ER PT J AU Miller, CL West, JA Bettini, AC Koerner, FC Gudewicz, TM Freer, PE Coopey, SB Gadd, MA Hughes, KS Smith, BL Rafferty, E Specht, MC AF Miller, Cynthia L. West, Jane A. Bettini, Anna C. Koerner, Frederick C. Gudewicz, Thomas M. Freer, Phoebe E. Coopey, Suzanne B. Gadd, Michele A. Hughes, Kevin S. Smith, Barbara L. Rafferty, Elizabeth Specht, Michelle C. TI Surgical excision of radial scars diagnosed by core biopsy may help predict future risk of breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Radial scar; Complex sclerosing lesion; Surgical excision; High-risk lesion; Atypia ID ATYPICAL DUCTAL HYPERPLASIA; COMPLEX SCLEROSING LESIONS; CARCINOMA IN-SITU; OF-THE-LITERATURE; NEEDLE-BIOPSY; PATHOLOGICAL CORRELATION; SCREENING-PROGRAM; ADJUVANT BREAST; FOLLOW-UP; MANAGEMENT AB Radial scars (RS's) are benign breast lesions known to be associated with carcinomas and other high-risk lesions (HRL's). The upgrade rate to carcinoma after core biopsy revealing RS is 0-40 %. We sought to determine the outcomes of RS with and without HRL diagnosed by core biopsy. Patients who underwent core biopsy revealing RS without carcinoma at our institution between 1/1996 and 11/2012 were identified from a surgical pathology database. Retrospective chart review was utilized to classify patients as RS-no HRL or RS-HRL. HRL was defined as ADH, LCIS, and/or ALH. We determined upgrade rate to carcinoma at surgical excision, and upgrade to HRL for RS-no HRL patients. Univariate analysis was performed to identify risk factors for upgrade in RS-no HRL patients. 156 patients underwent core biopsy revealing RS, 131 RS-no HRL (84 %), and 25 RS-HRL (16 %). The overall rate of upgrade to invasive carcinoma was 0.8 % (1/124). 1.0 % (1/102) of RS-no HRL and 13.6 % (3/22) of RS-HRL patients were upgraded to DCIS (P = 0.0023). The upgrade of RS-no HRL to HRL at excision was 21.6 % (22/102). By univariate analysis, RS-no HRL with radiologic appearance of a mass/architectural distortion had a significantly higher rate of upgrade to HRL or carcinoma compared with calcifications (P = 0.03). Excision of RS to rule out associated invasive carcinoma is not warranted, given a < 1 % rate of upgrade at excision. However, excision to evaluate for non-invasive cancer or HRL may be considered to help guide clinical decision-making about use of chemoprevention. C1 [Miller, Cynthia L.; Bettini, Anna C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [West, Jane A.; Freer, Phoebe E.; Rafferty, Elizabeth] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Koerner, Frederick C.; Gudewicz, Thomas M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Coopey, Suzanne B.; Gadd, Michele A.; Hughes, Kevin S.; Smith, Barbara L.; Specht, Michelle C.] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Specht, MC (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. EM mspecht@partners.org OI Hughes, Kevin/0000-0003-4084-6484; Freer, Phoebe/0000-0001-6886-7100 NR 48 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2014 VL 145 IS 2 BP 331 EP 338 DI 10.1007/s10549-014-2958-y PG 8 WC Oncology SC Oncology GA AH8FG UT WOS:000336370200006 PM 24748568 ER PT J AU Chen, WY Giobbie-Hurder, A Gantman, K Savoie, J Scheib, R Parker, LM Schernhammer, ES AF Chen, Wendy Y. Giobbie-Hurder, Anita Gantman, Kathryn Savoie, Jennifer Scheib, Rochelle Parker, Leroy M. Schernhammer, Eva S. TI A randomized, placebo-controlled trial of melatonin on breast cancer survivors: impact on sleep, mood, and hot flashes SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Melatonin; Sleep disturbance; Survivorship; Clinical trial ID PINEAL HORMONE MELATONIN; QUALITY-OF-LIFE; EXOGENOUS MELATONIN; DEPRESSIVE SYMPTOMS; DOUBLE-BLIND; CHEMOTHERAPY; THERAPY; WOMEN; METAANALYSIS; EFFICACY AB The purpose is to examine the effects of melatonin supplementation on sleep, mood, and hot flashes in postmenopausal breast cancer survivors. In a randomized, double-blind, placebo-controlled study, 95 postmenopausal women with a prior history of stage 0-III breast cancer, who had completed active cancer treatment (including hormonal therapy) were randomly assigned 1:1 to either 3 mg oral melatonin (n = 48) or placebo daily (n = 47) for 4 months. Sleep, mood, and hot flashes were assessed at baseline and 4 months via self-administered questionnaire using the Pittsburgh Sleep Quality Index (PSQI), Center for Epidemiologic Studies-Depression (CES-D), and the North Central Cancer Treatment Group (NCCTG) hot flash diary, respectively. Eighty-six women (91 %) completed the study and provided pre- and post-questionnaires. At baseline, 52 % of participants reported poor sleep in the month prior to enrollment. Compared to subjects on placebo, subjects randomized to melatonin experienced significantly greater improvements in subjective sleep quality as measured by the PSQI, including domains on sleep quality, daytime dysfunction and total score. For example, the mean change in PSQI score was -0.1 in the placebo group compared to -1.9 in the melatonin group (p < 0.001). There were no significant differences in measures of depression or hot flashes. Sleep disturbances are common among breast cancer survivors, even after completion of active cancer treatment. This is the first randomized placebo-controlled study among breast cancer survivors to demonstrate that melatonin was associated with an improvement in subjective sleep quality, without any significant adverse effects. C1 [Chen, Wendy Y.; Schernhammer, Eva S.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chen, Wendy Y.; Schernhammer, Eva S.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Wendy Y.; Savoie, Jennifer; Scheib, Rochelle; Parker, Leroy M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Gantman, Kathryn] Mt Auburn Hosp, Cambridge, MA USA. [Schernhammer, Eva S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Schernhammer, Eva S.] ACR ITR, Vienna, Austria. [Schernhammer, Eva S.] LBI ACR VIEnna CEADDP, Vienna, Austria. RP Chen, WY (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM wendy.chen@channing.harvard.edu FU National Cancer Institute [R03 CA123597] FX We are grateful to the participants of this trial, as well as to the staff at the Dana-Farber Cancer Institute that helped facilitate the trial's conduct. This study was supported by a grant from the National Cancer Institute (R03 CA123597). The funding source had no role in the design or analysis of the study or in the decision to submit the manuscript for publication. NR 35 TC 12 Z9 13 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2014 VL 145 IS 2 BP 381 EP 388 DI 10.1007/s10549-014-2944-4 PG 8 WC Oncology SC Oncology GA AH8FG UT WOS:000336370200011 PM 24718775 ER PT J AU Freedman, RA Vaz-Luis, I Barry, WT Lii, H Lin, NU Winer, EP Keating, NL AF Freedman, Rachel A. Vaz-Luis, Ines Barry, William T. Lii, Huichuan Lin, Nancy U. Winer, Eric P. Keating, Nancy L. TI Patterns of chemotherapy, toxicity, and short-term outcomes for older women receiving adjuvant trastuzumab-based therapy SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Non-standard chemotherapy; Toxicity; Outcomes; Older women ID HER2-POSITIVE BREAST-CANCER; SEER-MEDICARE DATA; ELDERLY-WOMEN; COMORBIDITY INDEX; POPULATION; PLUS; HER2; VALIDATION; SELECTION; SURVIVAL AB Limited data are available regarding patterns of chemotherapy receipt and treatment-related toxicities for older women receiving adjuvant trastuzumab-based therapy. We used surveillance, epidemiology and end results (SEER)-Medicare data to identify patients a parts per thousand yen66 years with stage I-III breast cancer treated during 2005-2009, who received trastuzumab-based therapy. We examined patterns of chemotherapy receipt, and using multivariable logistic regression, we examined associations of age and comorbidity with non-standard chemotherapy. In propensity-weighted cohorts of women receiving standard and non-standard trastuzumab-based therapy, we also examined rates of (1) hospital events during the first 6 months of chemotherapy and (2) short-term survival. Among 2,106 women, 29.7 % were aged a parts per thousand yen76 and 66 % had a comorbidity score = 0. Overall, 31.3 % of women received non-standard chemotherapy. Compared to patients aged 66-70, older patients more often received non-standard chemotherapy [adjusted odds ratio (OR) = 4.1, 95 % confidence interval (CI) = 3.40-4.92 (ages 76-80); OR = 15.3, 95 %CI = 9.92-23.67 (age a parts per thousand yen 80)]. However, comorbidity was not associated with receipt of non-standard chemotherapy. After propensity score adjustment, hospitalizations were more frequent in the standard (vs. non-standard) group (adjusted OR = 1.7, 95 % CI = 1.29-2.24). With a median follow-up of 2.8 years, 276 deaths occurred; the adjusted hazard ratio (HR) for death was lower in standard versus non-standard treated women (HR = 0.69, 95 % CI = 0.52-0.91). Among a population-based cohort of older women receiving trastuzumab, nearly one-third received non-standard chemotherapy, with the highest rates among the oldest women. Non-standard chemotherapy was associated with fewer toxicity-related hospitalizations but worse survival. Further exploration of treatment toxicities and outcomes for older women with HER2-positive breast cancer is warranted. C1 [Freedman, Rachel A.; Vaz-Luis, Ines; Lin, Nancy U.; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Vaz-Luis, Ines] Inst Med Mol, Lisbon, Portugal. [Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Lii, Huichuan] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. [Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org FU National Cancer Institute's Surveillance, Epidemiology and End Results Program [N01-PC-35136, N01-PC-35139, N02-PC-15105]; Centers for Disease Control and Prevention's National Program of Cancer Registries [U55/CCR921930-02]; National Cancer Institute Specialized Program of Research Excellence in Breast Cancer [NIH P50 CA089393]; CJL Foundation; ACT NOW fund; Susan G. Komen for the Cure; Fundacao para a Ciencia e Tecnologia [HMSP-ICS/0004/2011]; Dana-Farber Cancer Institute Friends Grant FX This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The authors acknowledge the efforts of the Applied Research Program, NCI; the Office of Research, Development and Information, CMS; Information Management Services (IMS), Inc.; and the Surveillance, Epidemiology, and End Results (SEER) Program tumor registries in the creation of the SEER-Medicare database. The collection of the California cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Public Health the National Cancer Institute, and the Centers for Disease Control and Prevention or their Contractors and Subcontractors is not intended nor should be inferred. The study was supported by the National Cancer Institute Specialized Program of Research Excellence in Breast Cancer (NIH P50 CA089393), the CJL Foundation (to W T Barry), ACT NOW fund, Susan G. Komen for the Cure (to E P Winer and N L Keating), Fundacao para a Ciencia e Tecnologia (HMSP-ICS/0004/2011, Career Development Award) (to I Vaz-Luis) and a Dana-Farber Cancer Institute Friends Grant (to R Freedman). NR 38 TC 10 Z9 10 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2014 VL 145 IS 2 BP 491 EP 501 DI 10.1007/s10549-014-2968-9 PG 11 WC Oncology SC Oncology GA AH8FG UT WOS:000336370200022 PM 24756187 ER PT J AU Stanton, AL Petrie, KJ Partridge, AH AF Stanton, Annette L. Petrie, Keith J. Partridge, Ann H. TI Contributors to nonadherence and nonpersistence with endocrine therapy in breast cancer survivors recruited from an online research registry SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Adherence; Tamoxifen; Aromatase inhibitor; Compliance ID WORKING ALLIANCE INVENTORY; ADJUVANT HORMONAL-THERAPY; MEDICATION ADHERENCE; PATIENT-ADHERENCE; OLDER WOMEN; SELF-REPORT; POSTMENOPAUSAL WOMEN; CLINICAL-PRACTICE; TAMOXIFEN; METAANALYSIS AB Rates of adherence and persistence with endocrine therapy regimens (i.e., tamoxifen, aromatase inhibitors) by breast cancer survivors are suboptimal, with negative implications for prognosis. This study identified potential contributors to nonadherence and nonpersistence. From an online breast cancer research registry (Army of Women) including approximately 51,000 breast cancer survivors, we recruited 1,371 women who currently were taking endocrine therapy and 94 nonpersisters (i.e., diagnosed during the prior 5 years and on endocrine therapy within the prior 12 months, but no longer taking it). Participants completed an online questionnaire assessing demographic/medical characteristics, general and cancer-related psychosocial variables (i.e., depressive symptoms, anxiety, patient-oncologist relationship quality, cancer recurrence worry, general symptoms), and endocrine therapy-specific variables (i.e., endocrine therapy-related symptoms, perceived endocrine therapy necessity, long-term therapy use concern, endocrine therapy-related emotions). Two weeks later, current users were re-contacted to complete an endocrine therapy adherence measure. In a final regression model, patient-reported nonadherence among current users was significantly associated with lower financial status, a prior switch in endocrine therapies, a poorer relationship with the oncologist, and lower perceived need for and more negative emotions regarding endocrine therapy (adjusted R (2) = 0.15, P < 0.001). In a final logistic regression model, endocrine therapy nonpersisters were significantly more likely than current users to report depressive symptoms, as well as more negative emotions and lower positive emotions related to endocrine therapy (adjusted R (2) = 0.10, P < 0.001). In addition to demographic/medical variables, several potentially modifiable psychosocial characteristics are likely to contribute to endocrine therapy nonadherence and nonpersistence. C1 [Stanton, Annette L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Ctr Canc Prevent & Control Res, Dept Psychol, Los Angeles, CA 90095 USA. [Stanton, Annette L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Ctr Canc Prevent & Control Res, Dept Psychiat Biobehav Sci, Los Angeles, CA 90095 USA. [Petrie, Keith J.] Univ Auckland, Dept Psychol Med, Auckland 1, New Zealand. [Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Stanton, AL (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Ctr Canc Prevent & Control Res, Dept Psychol, 1285 Franz Hall,Box 90095-1563, Los Angeles, CA 90095 USA. EM astanton@ucla.edu FU Breast Cancer Research Foundation FX This research was supported by funding from the Breast Cancer Research Foundation (Stanton). NR 52 TC 17 Z9 17 U1 5 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2014 VL 145 IS 2 BP 525 EP 534 DI 10.1007/s10549-014-2961-3 PG 10 WC Oncology SC Oncology GA AH8FG UT WOS:000336370200025 PM 24781972 ER PT J AU Kantarjian, HM Steensma, DP Light, DW AF Kantarjian, Hagop M. Steensma, David P. Light, Donald W. TI The Patient Protection and Affordable Care Act: Is it Good or Bad for Oncology? SO CANCER LA English DT Editorial Material ID LUNG-CANCER; STAGE AB The Patient Protection and Affordable Care Act (ACA) has many flaws that need to be addressed, but it is better than what was. Oncologists should advocate for the ACA and work on improving it. C1 [Kantarjian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Leukemia, Houston, TX 77030 USA. [Steensma, David P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Oncol,Dept Med, Boston, MA 02115 USA. [Light, Donald W.] Harvard Univ, Edmond J Safra Ctr Eth, Cambridge, MA 02138 USA. RP Kantarjian, HM (reprint author), Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Leukemia, 1400 Holcombe Blvd,Unit 428, Houston, TX 77030 USA. EM hkantarj@mdanderson.org OI Steensma, David/0000-0001-5130-9284 FU NCI NIH HHS [P30 CA016672] NR 21 TC 2 Z9 2 U1 1 U2 2 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 JUN 1 PY 2014 VL 120 IS 11 BP 1600 EP 1603 DI 10.1002/cncr.28673 PG 4 WC Oncology SC Oncology GA AI1OE UT WOS:000336619700004 PM 24643748 ER PT J AU Garcia, JA Hudes, GR Choueiri, TK Stadler, WM Wood, LS Gurtler, J Bhatia, S Joshi, A Hozak, RR Xu, YH Schwartz, JD Thompson, JA AF Garcia, Jorge A. Hudes, Gary R. Choueiri, Toni K. Stadler, Walter M. Wood, Laura S. Gurtler, Jayne Bhatia, Shailender Joshi, Adarsh Hozak, Rebecca R. Xu, Yihuan Schwartz, Jonathan D. Thompson, John A. TI A Phase 2, Single-Arm Study of Ramucirumab in Patients With Metastatic Renal Cell Carcinoma With Disease Progression on or Intolerance to Tyrosine Kinase Inhibitor Therapy SO CANCER LA English DT Article DE ramucirumab; renal cell carcinoma; phase 2; metastatic; monoclonal antibody ID PROGNOSTIC-FACTORS; III TRIAL; BEVACIZUMAB; SORAFENIB; SUNITINIB; TUMORS; SELECTION; GROWTH; CANCER AB BACKGROUNDMultitargeted tyrosine kinase inhibitors (TKIs) have antitumor activity in metastatic renal cell carcinoma (mRCC). Resistance to these agents develops frequently, and their use is often limited by intolerance. Ramucirumab is a recombinant human monoclonal antibody directed against human vascular endothelial growth factor receptor-2. For this study, the authors investigated the clinical efficacy and safety of ramucirumab in patients with TKI-resistant/intolerant mRCC. METHODSIn this single-arm phase 2 trial, patients received ramucirumab 8 mg/kg every 2 weeks until they developed disease progression or intolerable toxicity. The primary endpoint was the best objective response rate (ORR); additional endpoints included the disease control rate (DCR), progression-free survival (PFS), the median duration of overall response, and safety. RESULTSThirty-nine patients with RCC received ramucirumab monotherapy. Prior TKI therapy included sunitinib (59% of patients), sunitinib and sorafenib (30.8% of patients), and sorafenib (10.3% of patients). The ORR was 5.1% (95% confidence interval [CI], 0.6%-17.3%). The 12-week DCR was 64.1% (95% CI, 47.2%-78.8%). The median PFS was 7.1 months (95% CI, 4.1-9.7 months), and the median overall survival was 24.8 months (95% CI, 18.9-32.6 months). Grade 3 or higher adverse events that occurred in 5% of patients included grade 3 hypertension (7.7%) and proteinuria (5.1%). There was 1 on-study death from multiorgan failure. CONCLUSIONSAlthough the study did not meet its primary endpoint of 15% ORR, ramucirumab was associated with evidence of antitumor activity in patients with TKI-resistant/intolerant mRCC. Ramucirumab was safe and well tolerated. Cancer 2014;120:1647-1655. (c) 2014 American Cancer Society. C1 [Garcia, Jorge A.; Wood, Laura S.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44195 USA. [Hudes, Gary R.] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Stadler, Walter M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. [Gurtler, Jayne] Metarie Oncol, Metairie, LA USA. [Bhatia, Shailender; Thompson, John A.] Seattle Canc Care Alliance, Seattle, WA USA. [Bhatia, Shailender; Thompson, John A.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Joshi, Adarsh; Hozak, Rebecca R.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Xu, Yihuan; Schwartz, Jonathan D.] ImClone Syst Inc, Branchburg, NJ USA. RP Garcia, JA (reprint author), Cleveland Clin, Taussig Canc Inst, Dept Solid Tumor Oncol, Glickman Urol & Kidney Inst,CCF CWRU Lerner Coll, 9500 Euclid Ave R35, Cleveland, OH 44195 USA. EM garciaj4@ccf.org FU ImClone Systems LLC, a wholly owned subsidiary of Eli Lilly and Company FX This study was supported by ImClone Systems LLC, a wholly owned subsidiary of Eli Lilly and Company. NR 28 TC 16 Z9 16 U1 1 U2 5 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 JUN 1 PY 2014 VL 120 IS 11 BP 1647 EP 1655 DI 10.1002/cncr.28634 PG 9 WC Oncology SC Oncology GA AI1OE UT WOS:000336619700013 PM 24577874 ER PT J AU Abern, MR Terris, MK Aronson, WJ Kane, CJ Amling, CL Cooperberg, MR Freedland, SJ AF Abern, Michael R. Terris, Martha K. Aronson, William J. Kane, Christopher J. Amling, Christopher L. Cooperberg, Matthew R. Freedland, Stephen J. TI The Impact of Pathologic Staging on the Long-Term Oncologic Outcomes of Patients With Clinically High-Risk Prostate Cancer SO CANCER LA English DT Article DE prostatic neoplasms; prostatectomy; treatment outcome; pathology ID RADICAL PROSTATECTOMY; UNITED-STATES; MORTALITY; NOMOGRAM; SURVIVAL; DISEASE; NG/ML; MEN AB BACKGROUNDIn the prostate-specific antigen (PSA) screening era, approximately 15% of US men still present with clinically high-risk prostate cancer (PC). However, high-risk PC may be downgraded/downstaged at radical prostatectomy (RP), making additional therapy unnecessary. The authors tested the oncologic outcomes in men with clinically high-risk disease stratified on RP pathology. METHODSA total of 611 men with high-risk PC (PSA level>20 ng/mL, biopsy Gleason sum [bGS]8, or clinical classification ofT3) underwent RP and pelvic lymphadenectomy between 1998 and 2011. Outcomes included biochemical disease recurrence (BCR), receipt of androgen deprivation therapy (ADT), metastases, and PC-specific and overall survival. RP pathology was classified as unfavorable (pathologic Gleason sum8, pathologic classification ofT3, or lymph node-positive disease), or favorable (no unfavorable features). Multivariable analyses tested oncologic outcomes stratified by pathologic classification. RESULTSOverall, 527 men had complete pathologic data and were included in the current analysis. Of the cohort, 206 of 527 men (39%) had favorable pathology. This finding was more common in men with only 1 clinical high-risk feature, and a lower body mass index, PSA level, bGS, and percentage positive biopsy cores. Favorable pathology was associated with decreased BCR (hazards ratio [HR], 0.34), metastases (HR, 0.17), and PC death (HR, 0.17). After a median follow-up of 82 months (range, 49 months-131 months), 193 of the 527 men (37%) received ADT, including only 35 of the 206 men with favorable pathology (17%). Unfavorable pathology was associated with early ( 5 years) but not late treatment with ADT. CONCLUSIONSIn a large cohort of men with high-risk PC who were managed with RP, 39% had favorable pathology and superior oncologic outcomes. Cancer 2014;120:1656-1662. (c) 2014 American Cancer Society. C1 [Abern, Michael R.] Univ Illinois, Dept Urol, Chicago, IL 60612 USA. [Terris, Martha K.] Vet Affairs Med Ctr, Urol Sect, Augusta, GA USA. [Terris, Martha K.] Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. [Aronson, William J.] Vet Affairs Greater Los Angeles Healthcare Syst, Urol Sect, Dept Surg, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Kane, Christopher J.] Univ Calif San Diego, Div Urol, San Diego, CA 92103 USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR USA. [Cooperberg, Matthew R.] Univ Calif San Francisco, Ctr Comprehens Canc, Dept Urol, San Francisco, CA 94143 USA. [Cooperberg, Matthew R.] Vet Affairs Med Ctr, Dept Surg, Urol Sect, San Francisco, CA 94121 USA. [Freedland, Stephen J.] Vet Affairs Med Ctr, Urol Sect, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Sch Med, Dept Surg, Div Urol Surg, Durham, NC USA. RP Abern, MR (reprint author), Univ Illinois, Dept Urol, 820 S Wood St,Suite 515, Chicago, IL 60612 USA. EM mabern1@uic.edu OI Terris, Martha/0000-0002-3843-7270 NR 23 TC 10 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2014 VL 120 IS 11 BP 1656 EP 1662 DI 10.1002/cncr.28647 PG 7 WC Oncology SC Oncology GA AI1OE UT WOS:000336619700014 PM 24647966 ER PT J AU Steensma, DP Komrokji, RS Stone, RM List, AF Garcia-Manero, G Huber, JM Dennison, B Sekeres, MA AF Steensma, David P. Komrokji, Rami S. Stone, Richard M. List, Alan F. Garcia-Manero, Guillermo Huber, John M. Dennison, Betsy Sekeres, Mikkael A. TI Disparity in Perceptions of Disease Characteristics, Treatment Effectiveness, and Factors Influencing Treatment Adherence Between Physicians and Patients With Myelodysplastic Syndromes SO CANCER LA English DT Article DE myelodysplastic syndromes; therapy adherence; azacitidine; decitabine; lenalidomide; communication ID INTERNET-BASED SURVEY; CELL TRANSPLANTATION; AZACITIDINE; CANCER; IMPACT; DIAGNOSIS; SURVIVAL; LEUKEMIA; OUTCOMES; QUALITY AB BACKGROUNDPrevious studies have suggested that many patients with myelodysplastic syndromes (MDS) have an incomplete understanding of their disease, which may influence adherence to prescribed regimens and outcomes. METHODSTo better understand physician and patient perceptions about MDS and MDS therapy, the authors conducted 2 surveys in February 2012: 1 for patients with MDS and 1 for health care professionals (HCPs) who cared for patients with MDS. Patient and HCP surveys consisted of 57 and 49 questions, respectively, assessing understanding of MDS, perceptions of specific treatments, barriers to treatment adherence, and treatment experience. RESULTSIn total, 477 complete patient responses and 120 complete HCP responses were received. Among patient responders, 63% were aged 60 years, and 42% had received at least 1 disease-modifying therapy. Of the 61 physician responders, 57% practiced in an academic setting, and 43% practiced in the community; 71% of the 59 nonphysician HCPs worked in the community setting. Only 10% of patients agreed that MDS represented cancer compared with 59% of physicians and 46% of nonphysician HCPs (P<.001). Only 29% of patients reported that MDS was ever curable compared with 52% of physicians (P<.001). Physicians viewed the potential benefits of active therapy as greater than patients, but patients perceived the actual treatment experience more positively than physicians and differed from physicians in perceived reasons for stopping therapy. CONCLUSIONSPhysicians, nonphysician HCPs, and patients with MDS have disparate views of MDS characteristics and the value and limitations of treatments for MDS. Improved communication and education may increase understanding and achieve better treatment adherence and patient outcomes. Cancer 2014;120:1670-1676. (c) 2014 American Cancer Society. C1 [Steensma, David P.; Stone, Richard M.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02215 USA. [Komrokji, Rami S.; List, Alan F.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Med Oncol, Tampa, FL 33612 USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Huber, John M.] Aplast Anemia & Myelodysplast Syndromes Int Fdn, Rockville, MD USA. [Dennison, Betsy] Clar Commun, Pompton Lakes, NJ USA. [Sekeres, Mikkael A.] Cleveland Clin, Taussig Canc Inst, Dept Hematol Oncol & Blood Disorders, Cleveland, OH 44106 USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Adult Leukemia Program, 450 Brookline Ave,D2037, Boston, MA 02215 USA. EM david_steensma@dfci.harvard.edu OI Steensma, David/0000-0001-5130-9284 FU Celgene Corporation; Edward P. Evans Foundation FX This study was funded in part by an unrestricted educational grant to the Aplastic Anemia & Myelodysplastic Syndromes International Foundation from Celgene Corporation and by the Edward P. Evans Foundation. The authors designed and conducted the study and wrote the article without influence from the sponsor. NR 23 TC 12 Z9 12 U1 0 U2 0 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 JUN 1 PY 2014 VL 120 IS 11 BP 1670 EP 1676 DI 10.1002/cncr.28631 PG 7 WC Oncology SC Oncology GA AI1OE UT WOS:000336619700016 PM 24577838 ER PT J AU Ackerman, A Klein, O McDermott, DF Wang, W Ibrahim, N Lawrence, DP Gunturi, A Flaherty, KT Hodi, FS Kefford, R Menzies, AM Atkins, MB Long, GV Sullivan, RJ AF Ackerman, Allison Klein, Oliver McDermott, David F. Wang, Wei Ibrahim, Nageatte Lawrence, Donald P. Gunturi, Anasuya Flaherty, Keith T. Hodi, F. Stephen Kefford, Richard Menzies, Alexander M. Atkins, Michael B. Long, Georgina V. Sullivan, Ryan J. TI Outcomes of Patients With Metastatic Melanoma Treated With Immunotherapy Prior to or After BRAF Inhibitors SO CANCER LA English DT Article DE vemurafenib; sequencing; ipilimumab; melanoma; BRAF ID IMPROVED SURVIVAL; MEK INHIBITION; OPEN-LABEL; IPILIMUMAB; SAFETY; MULTICENTER; VEMURAFENIB; DABRAFENIB; RESPONSES; ANTI-PD-1 AB BACKGROUNDThe immunotherapy (IT) agents ipilimumab and interleukin-2 as well as BRAF inhibitors (BRAFi) vemurafenib and dabrafenib, with or without trametinib (MEK inhibitors), are all FDA-approved treatments for BRAF metastatic melanoma, but there are few studies to guide optimal sequencing. This retrospective analysis describes the outcomes of patients treated with either BRAFi before IT or IT before BRAFi. METHODSA cohort of patients treated with BRAFi alone or with MEK inhibitor was retrospectively identified. Response rate (RR), overall survival (OS), and progression-free survival (PFS) were evaluated for the entire cohort, subdivided by BRAFi prior to or after IT. RESULTSRR and median PFS and OS calculated from commencement of BRAFi following IT (N=32) were 57%, 6.7 months (95% confidence interval [CI]=4.3-9.1 months), and 19.6 months (95% CI=10.0-undefined months), respectively; whereas for BRAFi initially (N=242) were 66%, 5.6 months (95% CI=4.7-6.8 months), and 13.4 months (95% CI=10.1-17.0 months). Results were similar when controlled for prognostic variables. A total of 193 patients discontinued BRAFi, with OS of 2.9 months (range of 1.8-4.4 months) from day of BRAFi discontinuation. Forty patients subsequently received IT with ipilimumab. Only half could complete 4 doses of ipilimumab; PFS with ipilimumab was 2.7 months (95% CI=1.8-3.1 months) and OS was 5.0 months (95% CI=3.0-8.8 months). CONCLUSIONSIn this retrospective analysis, prior treatment with IT does not appear to negatively influence response to BRAFi. Outcomes for IT with ipilimumab following BRAFi discontinuation are poor. Randomized controlled trials are needed to define if sequencing IT prior to BRAFi therapy is superior to sequencing BRAFi prior to IT. Cancer 2014;120:1695-1701. (c) 2014 American Cancer Society. C1 [Ackerman, Allison; McDermott, David F.; Gunturi, Anasuya] Beth Israel Deaconess Med Ctr, Dept Med, Div Oncol, Boston, MA 02215 USA. [Klein, Oliver; Kefford, Richard] Westmead Hosp, Sydney, NSW, Australia. [Wang, Wei] Brigham & Womens Hosp, Div Sleep Med, Dept Med, Boston, MA 02115 USA. [Ibrahim, Nageatte; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Melanoma Dis Ctr, Boston, MA 02115 USA. [Lawrence, Donald P.; Flaherty, Keith T.; Sullivan, Ryan J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA USA. [Kefford, Richard; Long, Georgina V.] Westmead Hosp, Westmead Millennium Inst, Westmead Inst Canc Res, Sydney, NSW, Australia. [Kefford, Richard; Menzies, Alexander M.; Long, Georgina V.] Univ Sydney, Discipline Med, Sydney, NSW 2006, Australia. [Kefford, Richard; Menzies, Alexander M.; Long, Georgina V.] Melanoma Inst Australia, Sydney, NSW, Australia. [Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Sullivan, RJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM rsullivan7@partners.org NR 18 TC 70 Z9 74 U1 3 U2 23 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 JUN 1 PY 2014 VL 120 IS 11 BP 1695 EP 1701 DI 10.1002/cncr.28620 PG 7 WC Oncology SC Oncology GA AI1OE UT WOS:000336619700019 PM 24577748 ER PT J AU Meza, R ten Haaf, K Kong, CY Erdogan, A Black, WC Tammemagi, MC Choi, SE Jeon, J Han, SS Munshi, V van Rosmalen, J Pinsky, P McMahon, PM de Koning, HJ Eric, J Hazelton, WD Plevritis, SK AF Meza, Rafael ten Haaf, Kevin Kong, Chung Yin Erdogan, Ayca Black, William C. Tammemagi, Martin C. Choi, Sung Eun Jeon, Jihyoun Han, Summer S. Munshi, Vidit van Rosmalen, Joost Pinsky, Paul McMahon, Pamela M. de Koning, Harry J. Feuer, Eric J. Hazelton, William D. Plevritis, Sylvia K. TI Comparative Analysis of 5 Lung Cancer Natural History and Screening Models That Reproduce Outcomes of the NLST and PLCO Trials SO CANCER LA English DT Article DE Cancer Intervention and Surveillance Modeling Network (CISNET); comparative modeling analyses; low-dose CT screening; lung cancer screening; cancer natural history models; smoking and lung cancer; simulation model ID MULTISTAGE CARCINOGENESIS; MICROSIMULATION MODELS; POTENTIAL BENEFITS; COLORECTAL-CANCER; UNITED-STATES; MORTALITY; SMOKING; PROSTATE; HEALTH; RISK AB BACKGROUNDThe National Lung Screening Trial (NLST) demonstrated that low-dose computed tomography screening is an effective way of reducing lung cancer (LC) mortality. However, optimal screening strategies have not been determined to date and it is uncertain whether lighter smokers than those examined in the NLST may also benefit from screening. To address these questions, it is necessary to first develop LC natural history models that can reproduce NLST outcomes and simulate screening programs at the population level. METHODSFive independent LC screening models were developed using common inputs and calibration targets derived from the NLST and the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). Imputation of missing information regarding smoking, histology, and stage of disease for a small percentage of individuals and diagnosed LCs in both trials was performed. Models were calibrated to LC incidence, mortality, or both outcomes simultaneously. RESULTSInitially, all models were calibrated to the NLST and validated against PLCO. Models were found to validate well against individuals in PLCO who would have been eligible for the NLST. However, all models required further calibration to PLCO to adequately capture LC outcomes in PLCO never-smokers and light smokers. Final versions of all models produced incidence and mortality outcomes in the presence and absence of screening that were consistent with both trials. CONCLUSIONSThe authors developed 5 distinct LC screening simulation models based on the evidence in the NLST and PLCO. The results of their analyses demonstrated that the NLST and PLCO have produced consistent results. The resulting models can be important tools to generate additional evidence to determine the effectiveness of lung cancer screening strategies using low-dose computed tomography. Cancer 2014;120:1713-1724. (c) 2014 American Cancer Society. C1 [Meza, Rafael] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. [ten Haaf, Kevin; van Rosmalen, Joost; de Koning, Harry J.] Erasmus Univ, Med Ctr, Dept Publ Hlth, Rotterdam, Netherlands. [Kong, Chung Yin; Choi, Sung Eun; Munshi, Vidit; McMahon, Pamela M.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Kong, Chung Yin; Choi, Sung Eun; Munshi, Vidit; McMahon, Pamela M.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Erdogan, Ayca; Han, Summer S.; Plevritis, Sylvia K.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Black, William C.] Dartmouth Coll, Dept Radiol, Geisel Sch Med Dartmouth, Hanover, NH 03755 USA. [Tammemagi, Martin C.] Brock Univ, Dept Community Hlth Sci, St Catharines, ON L2S 3A1, Canada. [Jeon, Jihyoun; Hazelton, William D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98104 USA. [van Rosmalen, Joost] Erasmus Univ, Med Ctr, Dept Biostat, Rotterdam, Netherlands. [Pinsky, Paul] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Meza, R (reprint author), Univ Michigan, Dept Epidemiol, 1415 Washington Hts, Ann Arbor, MI 48109 USA. EM rmeza@umich.edu OI van Rosmalen, Joost/0000-0002-9187-244X FU Agency for Healthcare Research and Quality (AHRQ) [U01-CA152956] FX This report is based on research conducted by the National Cancer Institutes (NCI)'s Cancer Intervention and Surveillance Modeling Network (CISNET) through support from an interagency agreement with the Agency for Healthcare Research and Quality (AHRQ) (administrative supplement to NCI grant U01-CA152956). NR 31 TC 17 Z9 17 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUN 1 PY 2014 VL 120 IS 11 BP 1713 EP 1724 DI 10.1002/cncr.28623 PG 12 WC Oncology SC Oncology GA AI1OE UT WOS:000336619700021 PM 24577803 ER PT J AU Slusarz, KM Merker, VL Muzikansky, A Francis, SA Plotkin, SR AF Slusarz, Katherine M. Merker, Vanessa L. Muzikansky, Alona Francis, Sanjeev A. Plotkin, Scott R. TI Long-term toxicity of bevacizumab therapy in neurofibromatosis 2 patients SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Bevacizumab; Neurofibromatosis 2; Toxicity; Hypertension; Proteinuria ID BLOOD-PRESSURE; PHASE-III; HYPERTENSION; CANCER; TYPE-2; INHIBITORS; SYSTEM; TRIAL; RISK AB Bevacizumab treatment is associated with tumor shrinkage and hearing improvement in about 50 % of neurofibromatosis 2 (NF2) patients with progressive vestibular schwannomas. Hypertension and proteinuria are common side effects of treatment. However, the long-term toxicity of bevacizumab in this population has not been reported. We reviewed the medical records of all NF2 patients treated with compassionate care bevacizumab at our institution. Hypertension was defined as a systolic blood pressure a parts per thousand yen140 or a diastolic blood pressure a parts per thousand yen90. Proteinuria was measured by urine dipstick. Time-to-event analyses were conducted for hypertension and proteinuria. The relationship of cumulative dose of bevacizumab to mean arterial pressure (MAP) was examined using mixed model analysis, while the relationship to urine protein was examined using generalized estimating equations. Thirty-three patients (median age 28 years) were included in the study, with a median treatment time of 34.1 months. 15/26 (58 %) patients became hypertensive and 18/29 (62 %) developed proteinuria during treatment. Median time to develop hypertension was 12.8 months. Median time to develop 1+ and 2+ proteinuria was 23.7 and 31.9 months, respectively. Eight patients required treatment holidays for proteinuria (median length 3.2 months). A significant positive relationship existed between cumulative bevacizumab dose and MAP (p < 0.0001) but not between cumulative dose and proteinuria (p > 0.30). In our cohort of NF2 patients, extended use of bevacizumab was associated with manageable toxicity. However, bevacizumab treatment still requires careful monitoring of blood pressure and proteinuria, and future studies should investigate optimal dosing schedules to minimize long-term toxicity. C1 [Slusarz, Katherine M.] Massachusetts Gen Hosp, Ctr Neurofibromatosis & Allied Disorders, Ctr Human Genet Res, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Francis, Sanjeev A.] Massachusetts Gen Hosp, Serv Cardiol, Boston, MA 02114 USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org OI Merker, Vanessa/0000-0002-4542-5227 NR 24 TC 13 Z9 15 U1 0 U2 0 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 JUN PY 2014 VL 73 IS 6 BP 1197 EP 1204 DI 10.1007/s00280-014-2456-2 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AH8NV UT WOS:000336395700012 PM 24710627 ER PT J AU Yurgelun, MB Hornick, JL Curry, VK Ukaegbu, CI Brown, EK Hiller, E Chittenden, A Goldberg, JE Syngal, S AF Yurgelun, Matthew B. Hornick, Jason L. Curry, Victoriana K. Ukaegbu, Chinedu I. Brown, Emily K. Hiller, Elaine Chittenden, Anu Goldberg, Joel E. Syngal, Sapna TI Therapy-Associated Polyposis as a Late Sequela of Cancer Treatment SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Polyps; Radiation; Adenomas; Chemotherapy ID CHILDHOOD-CANCER; HODGKINS-DISEASE; 2ND MALIGNANCY; SURVIVORS; RISK; ADENOMAS; COHORT AB Survivors of childhood cancers are at increased risk of developing secondary gastrointestinal cancers, including colorectal cancer, later in life, possibly from exposure to abdominopelvic radiotherapy and/or alkylating chemotherapy. Profuse gastrointestinal polyposis is associated with rare, inherited colorectal cancer predisposition syndromes, most commonly caused by mutations in the adenomatous polyposis coli (APC) or mutY homolog (MUTYH) genes. We describe 5 patients who developed gastrointestinal polyposis many years after radiotherapy and chemotherapy for a childhood cancer. Genetic analysis of all 5 subjects did not identify pathogenic germline mutations in APC or MUTYH. Chemotherapy and/or radiotherapy therefore might cause gastrointestinal polyposis in some patients by undiscovered mechanisms. C1 [Yurgelun, Matthew B.; Curry, Victoriana K.; Ukaegbu, Chinedu I.; Brown, Emily K.; Hiller, Elaine; Chittenden, Anu] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Yurgelun, Matthew B.; Syngal, Sapna] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Goldberg, Joel E.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Goldberg, Joel E.] Harvard Univ, Sch Med, Boston, MA USA. RP Yurgelun, MB (reprint author), Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Matthew_Yurgelun@DFCI.Harvard.edu FU National Institutes of Health (National Cancer Institute) [K24CA113433] FX Supported by the National Institutes of Health (National Cancer Institute) (K24CA113433 to S.S.). NR 15 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 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUN PY 2014 VL 12 IS 6 BP 1046 EP 1050 DI 10.1016/j.cgh.2013.11.040 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH9ZI UT WOS:000336504700027 PM 24362051 ER PT J AU Pinto, N Gamazon, ER Antao, N Myers, J Stark, AL Konkashbaev, A Im, HK Diskin, SJ London, WB Ludeman, SM Maris, JM Cox, NJ Cohn, SL Dolan, ME AF Pinto, N. Gamazon, E. R. Antao, N. Myers, J. Stark, A. L. Konkashbaev, A. Im, H. K. Diskin, S. J. London, W. B. Ludeman, S. M. Maris, J. M. Cox, N. J. Cohn, S. L. Dolan, M. E. TI Integrating Cell-Based and Clinical Genome-Wide Studies to Identify Genetic Variants Contributing to Treatment Failure in Neuroblastoma Patients SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HIGH-RISK NEUROBLASTOMA; PHARMACOGENOMIC DISCOVERY; CYCLOPHOSPHAMIDE; SUSCEPTIBILITY; IDENTIFICATION; ASSOCIATION; STRESS; TRIAL; CYTOTOXICITY; METABOLITES AB High-risk neuroblastoma is an aggressive malignancy, with high rates of treatment failure. We evaluated genetic variants associated with in vitro sensitivity to two derivatives of cyclophosphamide for association with clinical response in a separate replication cohort of neuroblastoma patients (n = 2,709). To determine sensitivity, lymphoblastoid cell lines (LCLs) were exposed to increasing concentrations of 4-hydroperoxycyclophosphamide (4HC; n = 422) and phosphoramide mustard (PM; n = 428). Genome-wide association studies were performed to identify single-nucleotide polymorphisms (SNPs) associated with sensitivity to 4HC and PM. SNPs consistently associated with LCL sensitivity were analyzed for associations with event-free survival (EFS) in patients. Two linked SNPs, rs9908694 and rs1453560, were found to be associated with (i) sensitivity to PM in LCLs across populations and (ii) EFS in all patients (P = 0.01) and within the high-risk subset (P = 0.05). Our study highlights the value of cell-based models to identify candidate variants that may predict response to treatment in patients with cancer. C1 [Pinto, N.] Univ Chicago, Dept Pediat, Sect Pediat Hematol Oncol, Chicago, IL 60637 USA. [Gamazon, E. R.; Konkashbaev, A.; Cox, N. J.] Univ Chicago, Med Genet Sect, Dept Med, Chicago, IL 60637 USA. [Antao, N.; Myers, J.; Stark, A. L.; Dolan, M. E.] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Im, H. K.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Diskin, S. J.; Maris, J. M.] Univ Penn, Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Diskin, S. J.; Maris, J. M.] Univ Penn, Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Diskin, S. J.; Maris, J. M.] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [London, W. B.] Harvard Univ, Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [London, W. B.] Stat & Data Ctr, Childrens Oncol Grp, Arcadia, CA USA. [Ludeman, S. M.] Albany Coll Pharm & Hlth Sci, Dept Basic & Social Sci, Albany, NY USA. RP Dolan, ME (reprint author), Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. EM edolan@medicine.bsd.uchicago.edu OI Cohn, Susan/0000-0001-5749-7650; Gamazon, Eric/0000-0003-4204-8734 FU National Center For Advancing Translational Sciences of the National Institutes of Health (NIH) [UL1TR000430]; NIH/National Institute of General Medical Sciences Pharmacogenomics of Anticancer Agents grant [U01GM61393]; University of Chicago Breast Cancer SPORE grants [NCI P50 CA125183, NIH/NCI RO1 CA136765, NIH/NCI R01 CA 016783]; St. Baldrick's Foundation; Cancer Research Foundation FX Research reported in this publication was supported by the National Center For Advancing Translational Sciences of the National Institutes of Health (NIH) under award UL1TR000430, NIH/National Institute of General Medical Sciences Pharmacogenomics of Anticancer Agents grant U01GM61393, and by the University of Chicago Breast Cancer SPORE grants NCI P50 CA125183, NIH/NCI RO1 CA136765, and NIH/NCI R01 CA 016783. In addition, this research was supported by the St. Baldrick's Foundation and the Cancer Research Foundation. The authors are grateful to the Pharmacogenomics of Anticancer Agents Cell Line Core at the University of Chicago for assistance in maintaining the cell lines. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors thank Shannon Delaney for her help in formatting the IKZF3 siRNA results. NR 47 TC 4 Z9 4 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 2014 VL 95 IS 6 BP 644 EP 652 DI 10.1038/clpt.2014.37 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH8VC UT WOS:000336415300028 PM 24549002 ER PT J AU Danilack, VA Weston, NA Richardson, CR Mori, DL Moy, ML AF Danilack, Valery A. Weston, Nicole A. Richardson, Caroline R. Mori, DeAnna L. Moy, Marilyn L. TI Reasons Persons with COPD Do Not Walk and Relationship with Daily Step Count SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE exercise; pulmonary disease; accelerometer; physical activity; step count ID OBSTRUCTIVE PULMONARY-DISEASE; PHYSICAL-ACTIVITY; OLDER-ADULTS; BARRIERS; EXERCISE; POPULATION; PARTICIPATION; COHORT; REHABILITATION; ACCELEROMETER AB Background: Physical activity (PA) is significantly reduced in persons with COPD. Assessing reasons why persons with COPD do not engage in PA can guide development of effective interventions to promote PA. Methods: We queried 102 participants with stable COPD about disease-related and general reasons why they do not walk more. The StepWatch Activity Monitor (Orthocare Innovations, Mountlake Terrace, WA, USA) assessed daily step count, a direct measure of PA. Regression models assessed daily step count by response categories, adjusting for age and FEV1 % predicted. Results: Subjects had mean age 72 +/- 8 years and mean FEV1 1.48 +/- 0.55 L (52 +/- 19% predicted). COPD-related worries of becoming short of breath (SOB), needing to use inhalers, or oxygen level becoming low were endorsed by 31, 14, and 12 subjects, respectively. Controlling for age and FEV1% predicted, those who worried about becoming SOB walked an average of 1,329 fewer steps per day than those who did not worry (p = 0.020). Those who worried about needing to use inhalers walked an average of 1,806 fewer steps per day than those who did not worry (p = 0.016). Subjects who were the most motivated and confident walked significantly more than those who were the least motivated and confident. Conclusions: Presence of COPD-related reasons and lower motivation and confidence are associated with lower daily step count. Management of dyspnea and education about medication use during exercise, and strategies to increase motivation and confidence could facilitate walking in COPD. C1 [Danilack, Valery A.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Danilack, Valery A.; Weston, Nicole A.; Moy, Marilyn L.] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, West Roxbury, MA 02132 USA. [Richardson, Caroline R.] Univ Michigan, Sch Med, Dept Family Med, Ann Arbor, MI USA. [Richardson, Caroline R.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. [Mori, DeAnna L.] VA Boston Healthcare Syst, Psychol Serv, West Roxbury, MA 02132 USA. [Mori, DeAnna L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Moy, Marilyn L.] Vet Hlth Adm, Dept Vet Affairs, Rehabil Res & Dev Serv, Washington, DC USA. [Moy, Marilyn L.] Harvard Univ, Sch Med, Boston, MA USA. RP Moy, ML (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Sect, 1400 VFW Pkwy,Mail Code 111PI, West Roxbury, MA 02132 USA. EM marilyn.moy@va.gov FU Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research and Development Service through a VA Career Development Award; CIMIT: Center for Integration of Medicine and Innovative Technology, Boston, MA FX The research reported here was supported by the Department of Veteran Affairs, Veterans Health Administration, Rehabilitation Research and Development Service through a VA Career Development Award to Dr. Moy. Dr. Moy was supported in part by CIMIT: Center for Integration of Medicine and Innovative Technology, Boston, MA. The authors report no conflicts of interest. NR 46 TC 4 Z9 4 U1 3 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 EI 1541-2563 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD JUN PY 2014 VL 11 IS 3 BP 290 EP 299 DI 10.3109/15412555.2013.841670 PG 10 WC Respiratory System SC Respiratory System GA AI0AI UT WOS:000336507800006 PM 24152213 ER PT J AU O'Horo, JC Maki, DG Krupp, AE Safdar, N AF O'Horo, John C. Maki, Dennis G. Krupp, Anna E. Safdar, Nasia TI Arterial Catheters as a Source of Bloodstream Infection: A Systematic Review and Meta-Analysis SO CRITICAL CARE MEDICINE LA English DT Article DE arterial catheterization; catheter-related infections; critical care; meta-analysis; nosocomial infections; peripheral; prevalence ID CRITICALLY-ILL PATIENTS; RANDOMIZED CONTROLLED-TRIAL; CENTRAL VENOUS CATHETERS; INTENSIVE-CARE UNITS; RADIAL-ARTERY; FEMORAL-ARTERY; CARDIAC-SURGERY; COLONIZATION; CANNULATION; SEPSIS AB Objective: Catheter-related bloodstream infections are associated with significant costs and adverse consequences. Arterial catheters are commonly used in the critical care setting and are among the most heavily manipulated vascular access devices. We sought to evaluate the prevalence of arterial catheter-related bloodstream infection. Data Sources: PubMed, CinAHL, EMBASE, and Web of Science. Study Selection: Included studies reported prevalence rate of catheter-related bloodstream infection for arterial catheters used for critical illness or postoperative monitoring. For the purposes of this study, catheter-related bloodstream infection was defined as positive blood culture collected from an arterial catheter and from the periphery with the same organism in a patient demonstrating systemic signs of sepsis. Data Extraction: The study population, site of insertion, antiseptic preparation, catheter days, and prevalence of catheter-related bloodstream infection were abstracted. When data were not available, authors were contacted for further information. Data Synthesis: Forty-nine studies met criteria including 222 cases of arterial catheter-related bloodstream infection in 30,841 catheters. Pooled incidence was 3.40/1,000 catheters or 0.96/1,000 catheter days. Prevalence was considerably higher in the subgroup of studies that cultured all catheters (1.26/1,000 catheter days) compared with those studies that cultured only when the arterial catheter was suspected as the source for the catheter-related bloodstream infection (0.70/1,000 catheter days). Pooled data also found a significantly increased risk of infection for femoral site of insertion compared with radial artery for arterial catheter placement (relative risk, 1.93; 95% CI, 1.32-2.84; p = 0.001) Conclusions: Arterial catheters are an underrecognized cause of catheter-related bloodstream infection. Pooled incidence when catheters were systematically cultured and correlated to blood culture results indicated a substantial burden of arterial catheter-related bloodstream infection. Selection of a radial site over a femoral site will help reduce the risk of arterial catheter-related bloodstream infection. Future studies should evaluate technologies applied to preventing central venous catheter-related bloodstream infection to arterial catheters as well. C1 [O'Horo, John C.] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA. [Maki, Dennis G.; Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Krupp, Anna E.; Safdar, Nasia] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Sect Infect Dis, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. RP Safdar, N (reprint author), UW Med Fdn Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu RI O'Horo, John/N-8681-2013 OI O'Horo, John/0000-0002-0880-4498 NR 62 TC 25 Z9 26 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2014 VL 42 IS 6 BP 1334 EP 1339 DI 10.1097/CCM.0000000000000166 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA AH6UM UT WOS:000336266900016 PM 24413576 ER PT J AU Quraishi, SA Bittner, EA Blum, L McCarthy, CM Bhan, I Camargo, CA AF Quraishi, Sadeq A. Bittner, Edward A. Blum, Livnat McCarthy, Caitlin M. Bhan, Ishir Camargo, Carlos A., Jr. TI Prospective Study of Vitamin D Status at Initiation of Care in Critically III Surgical Patients and Risk of 90-Day Mortality SO CRITICAL CARE MEDICINE LA English DT Article DE 25-hydroxyvitamin; bioavailable 25-hydroxyvitamin; intensive care unit; mortality; vitamin D ID D DEFICIENCY; ILL PATIENTS; HEMODIALYSIS-PATIENTS; MINERAL METABOLISM; CRITICAL ILLNESS; UNIT; OUTCOMES; CALCIUM; ICU AB Objectives: 1) To characterize vitamin D status at initiation of critical care in surgical ICU patients and 2) to determine whether this vitamin D status is associated with the risk of prolonged hospital length of stay, 90-day readmission, and 90-day mortality. Design: Prospective cohort study. Setting: A teaching hospital in Boston, MA. Patients: Hundred surgical ICU patients. Interventions: None. Measurements and Main Results: Mean ( sd) serum total 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were 17 +/- 8 ng/mL and 32 +/- 19 pg/mL, respectively. Mean calculated bioavailable 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were 2.5 +/- 2.0 ng/mL and 6.6 +/- 5.3 pg/mL, respectively. Receiver-operating characteristic curve analysis demonstrated that all of four vitamin D measures predicted the three clinical outcomes; total 25-hydroxyvitamin D was not inferior to the other measures. Median (interquartile range) hospital length of stay was 11 days (8-19 d). Poisson regression analysis, adjusted for biologically plausible covariates, demonstrated an association of total 25-hydroxyvitamin D with hospital length of stay (incident rate ratio per 1 ng/mL, 0.98; 95% CI, 0.97-0.98). The 90-day readmission and mortality rates were 24% and 22%, respectively. Even after adjustment for biologically plausible covariates, there remained significant associations of total 25-hydroxyvitamin D with readmission (odds ratio per 1 ng/mL, 0.84; 95% CI, 0.74-0.95) and mortality (odds ratio per 1 ng/mL, 0.84; 95% CI, 0.73-0.97). Conclusions: Serum 25-hydroxyvitamin D levels within 24 hours of ICU admission may identify patients at high risk for prolonged hospitalization, readmission, and mortality. Randomized trials are needed to assess whether vitamin D supplementation can improve these clinically relevant outcomes in surgical ICU patients. C1 [Quraishi, Sadeq A.; Bittner, Edward A.; Blum, Livnat; McCarthy, Caitlin M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Quraishi, Sadeq A.; Bittner, Edward A.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. [Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Bhan, Ishir; Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Quraishi, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM squraishi@partners.org FU National Institutes of Health (NIH) [5T32GM007592-33, UL1 RR025758]; Harvard Medical School; NIH [K23 DK081677, R01 AI093723, U01 AI087881]; Massachusetts General Hospital FX Dr. Quraishi received grant support from the National Institutes of Health (NIH) (5T32GM007592-33 and UL1 RR025758) and Harvard Medical School and received support for article research from NIH. His institution received grant support from the NIH, Massachusetts General Hospital, and Harvard Medical School. Dr. Bhan received support for article research from NIH (K23 DK081677). His institution received grant support from NIH. Dr. Camargo Jr received support for article research from NIH (grants R01 AI093723 and U01 AI087881). His institution received grant support from NIH. Dr. Bittner received support for article research from the NIH. Dr. Blum received support for article research from the NIH. Dr. McCarthy received support for article research from the NIH. NR 24 TC 25 Z9 31 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2014 VL 42 IS 6 BP 1365 EP 1371 DI 10.1097/CCM.0000000000000210 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA AH6UM UT WOS:000336266900020 PM 24557421 ER PT J AU Goverman, J AF Goverman, Jeremy TI Our Natural Defense: The Skin! SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE antimicrobial peptides; barrier function; burn; permeability barrier; stratum corneum ID BURNS; DEATH; PEPTIDES C1 Massachusetts Gen Hosp, Div Burns, Boston, MA 02114 USA. RP Goverman, J (reprint author), Massachusetts Gen Hosp, Div Burns, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2014 VL 42 IS 6 BP 1575 EP 1577 DI 10.1097/CCM.0000000000000356 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA AH6UM UT WOS:000336266900065 PM 24836807 ER PT J AU Saddawi-Konefka, D Alston, TA AF Saddawi-Konefka, Daniel Alston, Theodore A. TI Tracking the Wily Speckle in Darkest Sepsis SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE bacteremia; Escherichia coli; myocardial edema; sepsis; strain echocardiography ID ESCHERICHIA-COLI; LEAKAGE; EDEMA C1 [Saddawi-Konefka, Daniel; Alston, Theodore A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Saddawi-Konefka, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2014 VL 42 IS 6 BP 1577 EP 1579 DI 10.1097/CCM.0000000000000353 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA AH6UM UT WOS:000336266900066 PM 24836808 ER PT J AU Dimas, AS Lagou, V Barker, A Knowles, JW Magi, R Hivert, MF Benazzo, A Rybin, D Jackson, AU Stringham, HM Song, C Fischer-Rosinsky, A Boesgaard, TW Grarup, N Abbasi, FA Assimes, TL Hao, K Yang, X Lecoeur, C Barroso, I Bonnycastle, LL Bottcher, Y Bumpstead, S Chines, PS Erdos, MR Graessler, J Kovacs, P Morken, MA Narisu, N Payne, F Stancakova, A Swift, AJ Tonjes, A Bornstein, SR Cauchi, S Froguel, P Meyre, D Schwarz, PEH Haring, HU Smith, U Boehnke, M Bergman, RN Collins, FS Mohlke, KL Tuomilehto, J Quertemous, T Lind, L Hansen, T Pedersen, O Walker, M Pfeiffer, AFH Spranger, J Stumvoll, M Meigs, JB Wareham, NJ Kuusisto, J Laakso, M Langenberg, C Dupuis, J Watanabe, RM Florez, JC Ingelsson, E McCarthy, MI Prokopenko, I AF Dimas, Antigone S. Lagou, Vasiliki Barker, Adam Knowles, Joshua W. Maegi, Reedik Hivert, Marie-France Benazzo, Andrea Rybin, Denis Jackson, Anne U. Stringham, Heather M. Song, Ci Fischer-Rosinsky, Antje Boesgaard, Trine Wellov Grarup, Niels Abbasi, Fahim A. Assimes, Themistocles L. Hao, Ke Yang, Xia Lecoeur, Cecile Barroso, Ines Bonnycastle, Lori L. Boettcher, Yvonne Bumpstead, Suzannah Chines, Peter S. Erdos, Michael R. Graessler, Jurgen Kovacs, Peter Morken, Mario A. Narisu, Narisu Payne, Felicity Stancakova, Alena Swift, Amy J. Toenjes, Anke Bornstein, Stefan R. Cauchi, Stephane Froguel, Philippe Meyre, David Schwarz, Peter E. H. Haering, Hans-Ulrich Smith, Ulf Boehnke, Michael Bergman, Richard N. Collins, Francis S. Mohlke, Karen L. Tuomilehto, Jaakko Quertemous, Thomas Lind, Lars Hansen, Torben Pedersen, Oluf Walker, Mark Pfeiffer, Andreas F. H. Spranger, Joachim Stumvoll, Michael Meigs, James B. Wareham, Nicholas J. Kuusisto, Johanna Laakso, Markku Langenberg, Claudia Dupuis, Josee Watanabe, Richard M. Florez, Jose C. Ingelsson, Erik McCarthy, Mark I. Prokopenko, Inga CA MAGIC Investigators TI Impact of Type 2 Diabetes Susceptibility Variants on Quantitative Glycemic Traits Reveals Mechanistic Heterogeneity SO DIABETES LA English DT Article ID BETA-CELL FUNCTION; SCALE ASSOCIATION ANALYSIS; BODY-MASS INDEX; INSULIN SENSITIVITY; PROINSULIN LEVELS; COMMON VARIANT; TCF7L2 GENE; GLUCOSE; GENOME; LOCI AB Patients with established type 2 diabetes display both beta-cell dysfunction and insulin resistance. To define fundamental processes leading to the diabetic state, we examined the relationship between type 2 diabetes risk variants at 37 established susceptibility loci, and indices of proinsulin processing, insulin secretion, and insulin sensitivity. We included data from up to 58,614 nondiabetic subjects with basal measures and 17,327 with dynamic measures. We used additive genetic models with adjustment for sex, age, and BMI, followed by fixed-effects, inverse-variance meta-analyses. Cluster analyses grouped risk loci into five major categories based on their relationship to these continuous glycemic phenotypes. The first cluster (PPARG, KLF14, IRS1, GCKR) was characterized by primary effects on insulin sensitivity. The second cluster (MTNR1B, GCK) featured risk alleles associated with reduced insulin secretion and fasting hyperglycemia. ARAP1 constituted a third cluster characterized by defects in insulin processing. A fourth cluster (TCF712, SLC30A8, HHEX/IDE, CDKAL1, CDKN2A/2B) was defined by loci influencing insulin processing and secretion without a detectable change in fasting glucose levels. The final group contained 20 risk loci with no clear-cut associations to continuous glycemic traits. By assembling extensive data on continuous glycemic traits, we have exposed the diverse mechanisms whereby type 2 diabetes risk variants impact disease predisposition. C1 [Dimas, Antigone S.; Lagou, Vasiliki; Maegi, Reedik; Ingelsson, Erik; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Dimas, Antigone S.] Biomed Sci Res Ctr, Athens, Greece. [Lagou, Vasiliki; Maegi, Reedik; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Barker, Adam; Wareham, Nicholas J.; Langenberg, Claudia] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England. [Knowles, Joshua W.; Abbasi, Fahim A.; Assimes, Themistocles L.; Quertemous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Knowles, Joshua W.; Abbasi, Fahim A.; Assimes, Themistocles L.; Quertemous, Thomas] Stanford Univ, Sch Med, Cardiovasc Inst, Stanford, CA 94305 USA. [Maegi, Reedik] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, Marie-France; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Benazzo, Andrea] Univ Ferrara, Dept Biol & Evolut, I-44100 Ferrara, Italy. [Rybin, Denis] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA. [Jackson, Anne U.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Jackson, Anne U.; Stringham, Heather M.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Song, Ci; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden. [Song, Ci] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Fischer-Rosinsky, Antje; Pfeiffer, Andreas F. H.; Spranger, Joachim] Charite, Dept Endocrinol & Metab, D-13353 Berlin, Germany. [Boesgaard, Trine Wellov] Steno Diabet Ctr, DK-2820 Gentofte, Denmark. [Grarup, Niels; Hansen, Torben; Pedersen, Oluf] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark. [Hao, Ke] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY USA. [Yang, Xia] Univ Calif Los Angeles, Dept Integrat Biol & Physiol, Los Angeles, CA USA. [Lecoeur, Cecile; Cauchi, Stephane; Froguel, Philippe; Meyre, David] Univ Lille 2, Inst Pasteur, Inst Biol, CNRS,UMR8199, Lille, France. [Barroso, Ines; Bumpstead, Suzannah; Payne, Felicity] Wellcome Trust Sanger Inst, Hinxton, England. [Barroso, Ines] Univ Cambridge, Metab Res Labs, Cambridge, England. [Barroso, Ines] Addenbrookes Hosp, Natl Inst Hlth Res, Cambridge Biomed Res Ctr, Inst Metab Sci, Cambridge, England. [Bonnycastle, Lori L.; Chines, Peter S.; Erdos, Michael R.; Morken, Mario A.; Narisu, Narisu; Swift, Amy J.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Boettcher, Yvonne; Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Med Ctr, IFB AdiposityDis, D-04109 Leipzig, Germany. [Graessler, Jurgen; Bornstein, Stefan R.; Schwarz, Peter E. H.] Univ Dresden, Div Prevent & Care Diabet, Dept Med 3, Dresden, Germany. [Kovacs, Peter] Interdisciplinary Ctr Clin Res Leipzig, Leipzig, Germany. [Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Stancakova, Alena; Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Toenjes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, D-04109 Leipzig, Germany. [Froguel, Philippe; Prokopenko, Inga] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London, England. [Meyre, David] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Haering, Hans-Ulrich] Univ Tubingen, Dept Internal Med, Div Endocrinol Diabetol Vasc Med Nephrol & Clin C, Tubingen, Germany. [Smith, Ulf] Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Lundberg Lab Diabet Res,Ctr Excellence Metab & Ca, Gothenburg, Sweden. [Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland. [Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria. [Tuomilehto, Jaakko] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Lind, Lars] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden. [Hansen, Torben] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark. [Pedersen, Oluf] Hagedorn Res Inst, Copenhagen, Denmark. [Pedersen, Oluf] Univ Copenhagen, Fac Hlth Sci, Inst Biomed Sci, Copenhagen, Denmark. [Pedersen, Oluf] Univ Aarhus, Fac Hlth Sci, Aarhus, Denmark. [Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Pfeiffer, Andreas F. H.] German Inst Human Nutr, Dept Clin Nutr, Nuthetal, Germany. [Meigs, James B.; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Watanabe, Richard M.] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [McCarthy, Mark I.] Churchill Hosp, Biomed Res Ctr, Oxford Natl Inst Hlth Res, Oxford OX3 7LJ, England. RP Prokopenko, I (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. EM rwatanab@usc.edu; jcflorez@partners.org; erik.ingelsson@medsci.uu.se; mark.mccarthy@drl.ox.ac.uk; i.prokopenko@imperial.ac.uk RI Grarup, Niels/K-2807-2015; Prokopenko, Inga/H-3241-2014; Schwarz, Peter/B-5127-2013; OI Grarup, Niels/0000-0001-5526-1070; Prokopenko, Inga/0000-0003-1624-7457; Schwarz, Peter/0000-0001-6317-7880; Magi, Reedik/0000-0002-2964-6011; Song, Ci/0000-0002-0947-9068; Rybin, Denis/0000-0002-3657-4829; Assimes, Themistocles/0000-0003-2349-0009; Payne, Felicity/0000-0003-4228-581X FU European Community [HEALTH-F4-2007-201413, LSHM-CT-2004-512013]; Wellcome Trust [WT098051, 098381]; Cambridge Biomedical Research Centre of the U.K. National Institute for Health Research; Medical Research Council Centre for Obesity and Related Metabolic Diseases; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; Affymetrix Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01 DK-078616]; NIDDK [K24 DK-080140]; Doris Duke Charitable Foundation Clinical Scientist Development Award; NIH [DK-069922, U54 DA021519, DK-062370, DK-072193, RR01066]; National Human Genome Research Institute [1 Z01 HG000024]; Agence Nationale de la Recherche; Conseil Regional Nord-Pas de Calais/Fonds europeen de developpement economique et regional; Academy of Finland [124243]; Clinical Research Group [KFO218/1]; Deutsche Forschungsgemeinschaft (DFG) [SP716/2-1]; German Bundesministerium fur Bildung und Forschung (BMBF); Mallinckrodt General Clinical Research Program, National Center for Research Resources; Swedish Research Council; Swedish Heart-Lung Foundation; Swedish Foundation for Strategic Research; Royal Swedish Academy of Science; Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention; Care; Danish Diabetes Association; Danish Research Council; European Union [QLG1-CT-2001-01252]; AstraZeneca; German Research Council [SF8-1052]; German Diabetes Association; Diabetes Hi Ifs; Forschungsfonds Deutschland; Boehringer Ingelheim Foundation; BMBF [FKZ: 01E01001]; European Commission under the Marie Curie Intra-European Fellowship; European Foundation; National Center for Research Resources, NIH [2 M01 RR000070]; U.S. Public Health Service; American Heart Association Fellow [10FTF3360005] FX The major funding for this meta-analysis was provided through the Seventh Framework Programme of the European Community (FP7/2007-2013), the ENGAGE project, and grant agreement HEALTH-F4-2007-201413. As part of the Ely Study, I.B. was supported by Wellcome Trust grant WT098051, the Cambridge Biomedical Research Centre of the U.K. National Institute for Health Research, and the Medical Research Council Centre for Obesity and Related Metabolic Diseases. The EUGENE2 Study was supported by grant LSHM-CT-2004-512013 from the European Community FP6 EUGENE2. The Framingham Heart Study was conducted in part using data and resources from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource project. This work was partially supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195) and its contract with Affymetrix Inc. for genotyping services (contract no. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II), which is funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. The Framingham Heart Study was also supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R01 DK-078616 to J.B.M., J.D., and J.C.F.; NIDDK grant K24 DK-080140 to J.B.M.; and a Doris Duke Charitable Foundation Clinical Scientist Development Award to J.C.F. Support for the Finland-United States Investigation of NIDDM Genetics was provided by NIH grants DK-069922 (to R.M.W.), U54 DA021519 (to R.M.W.), DK-062370 (to M.B.), and DK-072193 (to K.L.M.). Additional support comes from the National Human Genome Research Institute intramural project number 1 Z01 HG000024 (to F.S.C.). The Metabolisches Syndrom Berlin Potsdam (MESYBEPO) Study was supported by grants from Agence Nationale de la Recherche and Conseil Regional Nord-Pas de Calais/Fonds europeen de developpement economique et regional. Support for the Metabolic Syndrome in Men Study was provided by grant 124243 from the Academy of Finland. In the MESYBEPO Study, J.S. was supported by Clinical Research Group grant KFO218/1, Heisenberg Professorship SP716/2-1 of the Deutsche Forschungsgemeinschaft (DFG), and a research group on molecular nutrition of the German Bundesministerium fur Bildung und Forschung (BMBF). The Partners/Roche Cohort was supported by the Mallinckrodt General Clinical Research Program, National Center for Research Resources, and NIH grant RR01066. In the Prospective Investigation of the Vasculature in Uppsala Seniors and the Uppsala Longitudinal Study of Adult Men, the SNP Technology Platform is supported by Uppsala University, Uppsala University Hospital, and the Swedish Research Council for Infrastructures. El. was supported by grants from the Swedish Research Council, the Swedish Heart-Lung Foundation, the Swedish Foundation for Strategic Research, and the Royal Swedish Academy of Science. The QTL families and UNG92 Study is supported by the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention, and Care, The Danish Diabetes Association, and The Danish Research Council.; The Relationship between Insulin Sensitivity and Cardiovascular Disease Study is supported by European Union grant QLG1-CT-2001-01252 and AstraZeneca. The Sorbs Study was supported by grants from the German Research Council (SF8-1052 "Obesity mechanisms") and the German Diabetes Association and the Diabetes Hi Ifs und Forschungsfonds Deutschland. P.K. is funded by the Boehringer Ingelheim Foundation. The Integrated Research and Treatment Center Adiposity Diseases is supported by BMBF grant FKZ: 01E01001. I.P. and V.L. were partially funded through the Seventh Framework Programme of the European Community (grant FP7/2007-2013) and the ENGAGE project grant agreement HEALTH-F4-2007-201413. R.M. is funded by the European Commission under the Marie Curie Intra-European Fellowship and a European Foundation for the Study of Diabetes New Horizons grant. M.I.M. is supported by Wellcome Trust grant 098381. Sample collection for the Stanford IST Cohort was carried out in part in the Clinical and Translational Research Unit, Stanford University, with funds provided by the National Center for Research Resources, NIH grant 2 M01 RR000070, and the U.S. Public Health Service. J.W.K. is supported by American Heart Association Fellow to Faculty Transition award 10FTF3360005. NR 44 TC 77 Z9 79 U1 4 U2 32 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 JUN PY 2014 VL 63 IS 6 BP 2158 EP 2171 DI 10.2337/db13-0949 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI1VS UT WOS:000336643900039 PM 24296717 ER PT J AU Vassy, JL Hivert, MF Porneala, B Dauriz, M Florez, JC Dupuis, J Siscovick, DS Fornage, M Rasmussen-Torvik, LJ Bouchard, C Meigs, JB AF Vassy, Jason L. Hivert, Marie-France Porneala, Bianca Dauriz, Marco Florez, Jose C. Dupuis, Josee Siscovick, David S. Fornage, Myriam Rasmussen-Torvik, Laura J. Bouchard, Claude Meigs, James B. TI Polygenic Type 2 Diabetes Prediction at the Limit of Common Variant Detection SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISMS; DENSITY-LIPOPROTEIN-CHOLESTEROL; LIFE-STYLE INTERVENTION; RISK-FACTORS; AFRICAN-AMERICANS; GLUCOSE-TOLERANCE; RECLASSIFICATION; POPULATION; MELLITUS AB Genome-wide association studies (GWAS) may have reached their limit of detecting common type 2 diabetes (T2D)-associated genetic variation. We evaluated the performance of current polygenic T2D prediction. Using data from the Framingham Offspring (FOS) and the Coronary Artery Risk Development in Young Adults (CARDIA) studies, we tested three hypotheses: 1) a 62-locus genotype risk score (GRS(t)) improves T2D prediction compared with previous less inclusive GRS(t); 2) separate GRS for beta-cell (GRS(beta)) and insulin resistance (GRS(IR)) independently predict T2D; and 3) the relationships between T2D and GRS(t), GRS(beta), or GRS(IR) do not differ between blacks and whites. Among 1,650 young white adults in CARDIA, 820 young black adults in CARDIA, and 3,471 white middle-aged adults in FOS, cumulative T2D incidence was 5.9%, 14.4%, and 12.9%, respectively, over 25 years. The 62-locus GRS(t) was significantly associated with incident T2D in all three groups. In FOS but not CARDIA, the 62-locus GRSt improved the model C statistic (0.698 and 0.726 for models without and with GRS(t), respectively; P < 0.001) but did not materially improve risk reclassification in either study. Results were similar among blacks compared with whites. The GRS(beta) but not GRS(IR) predicted incident T2D among FOS and CARDIA whites. At the end of the era of common variant discovery for T2D, polygenic scores can predict T2D in whites and blacks but do not outperform clinical models. Further optimization of polygenic prediction may require novel analytic methods, including less common as well as functional variants. C1 [Vassy, Jason L.; Hivert, Marie-France; Dauriz, Marco; Florez, Jose C.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Vassy, Jason L.] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA USA. [Vassy, Jason L.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Hivert, Marie-France] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada. [Porneala, Bianca; Dauriz, Marco; Meigs, James B.] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. [Dauriz, Marco] Univ Verona Med Sch & Hosp Trust Verona, Div Endocrinol & Metab Dis, Dept Med, Verona, Italy. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Dupuis, Josee] Boston Univ Sch Publ Hlth, Depat Biostat, Boston, MA USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA. [Rasmussen-Torvik, Laura J.] Northwestern Univ Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. [Bouchard, Claude] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA USA. RP Meigs, JB (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM jmeigs@partners.org RI Bouchard, Claude/A-7637-2009; Dauriz, Marco/S-5843-2016 OI Dauriz, Marco/0000-0002-5542-5941 FU National Institutes of Health [R01-DK-078616, K24-DK-080140, U01-HG-006500, L30-DK089597]; National Heart, Lung, and Blood Institute (NHLBI); University of Alabama at Birmingham [HHSN268201300025C, HHSN268201300026C]; Northwestern University [HHSN268201300027C]; University of Minnesota [HHSN268201300028C]; Kaiser Foundation Research Institute [HHSN268201300029C]; Johns Hopkins University School of Medicine [HHSN268200900041C]; Intramural Research Program of the National Institute on Aging; NHLBI [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278] FX This work was supported by National Institutes of Health grants (R01-DK-078616 and K24-DK-080140 to J.B.M. and U01-HG-006500 and L30-DK089597 to J.L.V.). The CARDIA Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201300025C and HHSN268201300026C), Northwestern University (HHSN268201300027C), University of Minnesota (HHSN268201300028C), Kaiser Foundation Research Institute (HHSN268201300029C), and Johns Hopkins University School of Medicine (HHSN268200900041C). CARDIA is also partially supported by the Intramural Research Program of the National Institute on Aging. This manuscript was reviewed by CARDIA personnel for scientific content. The Framingham Heart Study was supported by the NHLBI (contract number N01-HC-25195) and its contract with Affymetrix, Inc., for genotyping services (contract number N02-HL-6-4278). A portion of this research was conducted using the Linux Clusters for Genetic Analysis (LinGA) computing resources at the Boston University Medical Campus. NR 44 TC 44 Z9 44 U1 0 U2 18 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 JUN PY 2014 VL 63 IS 6 BP 2172 EP 2182 DI 10.2337/db13-1663 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI1VS UT WOS:000336643900040 PM 24520119 ER PT J AU Inoue, T Higashiyama, M Kaji, I Rudenkyy, S Higuchi, K Guth, PH Engel, E Kaunitz, JD Akiba, Y AF Inoue, Takuya Higashiyama, Masaaki Kaji, Izumi Rudenkyy, Sergiy Higuchi, Kazuhide Guth, Paul H. Engel, Eli Kaunitz, Jonathan D. Akiba, Yasutada TI Dipeptidyl Peptidase IV Inhibition Prevents the Formation and Promotes the Healing of Indomethacin-Induced Intestinal Ulcers in Rats SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Glucagon-like peptide-2; NSAIDs; Taste receptor ID GLUCAGON-LIKE PEPTIDE-2; SHORT-BOWEL SYNDROME; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GROWTH-FACTOR-I; INDUCED ENTEROPATHY; ENTERAL NUTRIENTS; BICARBONATE SECRETION; AMINO-ACID; BLOOD-LOSS; GLP-2 AB We studied the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) as a possible therapy for non-steroidal anti-inflammatory drug (NSAID)-induced intestinal ulcers. Luminal nutrients release endogenous GLP-2 from enteroendocrine L cells. Since GLP-2 is degraded by dipeptidyl peptidase IV (DPPIV), we hypothesized that DPPIV inhibition combined with luminal administration of nutrients potentiates the effects of endogenous GLP-2 on intestinal injury. Intestinal injury was induced by indomethacin (10 mg/kg, sc) in fed rats. The long-acting DPPIV inhibitor K579 was given intragastrically (ig) or intraperitoneally (ip) before or after indomethacin treatment. l-Alanine (l-Ala) and inosine 5'-monophosphate (IMP) were co-administered ig after the treatment. Indomethacin treatment induced intestinal ulcers that gradually healed after treatment. Pretreatment with ig or ip K579 given at 1 mg/kg reduced total ulcer length, whereas K579 at 3 mg/kg had no effect. Exogenous GLP-2 also reduced intestinal ulcers. The preventive effect of K579 was dose-dependently inhibited by a GLP-2 receptor antagonist. Daily treatment with K579 (1 mg/kg), GLP-2, or l-Ala + IMP after indomethacin treatment reduced total ulcer length. Co-administration (ig) of K579 and l-Ala + IMP further accelerated intestinal ulcer healing. DPPIV inhibition and exogenous GLP-2 prevented the formation and promoted the healing of indomethacin-induced intestinal ulcers, although high-dose DPPIV inhibition reversed the preventive effect. Umami receptor agonists also enhanced the healing effects of the DPPIV inhibitor. The combination of DPPIV inhibition and luminal nutrient-induced GLP-2 release may be a useful therapeutic tool for the treatment of NSAIDs-induced intestinal ulcers. C1 [Inoue, Takuya; Higashiyama, Masaaki; Kaji, Izumi; Kaunitz, Jonathan D.; Akiba, Yasutada] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Inoue, Takuya; Higuchi, Kazuhide] Osaka Med Coll, Dept Internal Med 2, Osaka, Japan. [Rudenkyy, Sergiy; Guth, Paul H.; Kaunitz, Jonathan D.; Akiba, Yasutada] Greater Los Angles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Engel, Eli] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA. [Kaunitz, Jonathan D.; Akiba, Yasutada] Brentwood Biomed Res Inst, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] West Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), West Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU Department of Veterans Affairs Merit Review Award, NIH-NIDDK [R01 DK54221]; NIH-NIDDK [P30 DK0413] FX We thank Coleen and Bea Palileo for their assistance with manuscript preparation. Supported by the Department of Veterans Affairs Merit Review Award, NIH-NIDDK R01 DK54221 (J. Kaunitz), and the animal core of NIH-NIDDK P30 DK0413 (J.E. Rozengurt). NR 53 TC 12 Z9 12 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 2014 VL 59 IS 6 BP 1286 EP 1295 DI 10.1007/s10620-013-3001-6 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH8KF UT WOS:000336386000031 PM 24379150 ER PT J AU Hildebrandt, T Shope, S Varangis, E Klein, D Pfaff, DW Yehuda, R AF Hildebrandt, Tom Shope, Sydney Varangis, Eleanna Klein, Diane Pfaff, Donald W. Yehuda, Rachel TI Exercise reinforcement, stress, and beta-endorphins: An initial examination of exercise in anabolic-androgenic steroid dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Anabolic androgenic steroids; beta-endorphin; Cortisol; ACTH; Compulsive exercise; Drug dependence ID HEAVY-RESISTANCE EXERCISE; HEALTHY-YOUNG MEN; ACUTE HORMONAL RESPONSES; GROWTH-FACTOR RESPONSES; RAT-BRAIN; NANDROLONE DECANOATE; ANOREXIA-NERVOSA; PLASMA-CORTISOL; DOSE-RESPONSE; MALE HAMSTERS AB Background: Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. Method: Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity x frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, beta-endorphin samples, and measures of mood, compulsive exercise, and body image. Results: Between group differences indicated that on-cycle AAS users had the highest beta-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest beta-endorphin levels. Exercise value was positively correlated with beta-endorphin and symptoms of AAS dependence. Conclusion: The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Hildebrandt, Tom; Shope, Sydney; Varangis, Eleanna; Yehuda, Rachel] Ichan Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Klein, Diane] NYU, Dept Psychiat, New York, NY 10016 USA. [Pfaff, Donald W.] Rockefeller Univ, New York, NY 10021 USA. [Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Hildebrandt, T (reprint author), Ichan Sch Med Mt Sinai, Eating & Weight Disorders Program, Dept Psychiat, One Gustave Levy Pl,Box 1230, New York, NY 10029 USA. EM hildebtb@hotmail.com OI Hildebrandt, Thomas/0000-0001-7054-9590 FU NIDA K23 grant [DA024043] FX Funds for this study were provided by NIDA K23 grant DA024043 awarded to Dr. Hildebrandt. NIDA had no influence over the study design, execution of the project, interpretation or results, or manuscript preparation. NR 58 TC 1 Z9 1 U1 2 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 1 PY 2014 VL 139 BP 86 EP 92 DI 10.1016/j.drugalcdep.2014.03.008 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA AI2SI UT WOS:000336708000012 PM 24690349 ER PT J AU Rautiainen, S Wang, L Gaziano, JM Sesso, HD AF Rautiainen, Susanne Wang, Lu Gaziano, J. Michael Sesso, Howard D. TI Who uses multivitamins? A cross-sectional study in the Physicians' Health Study SO EUROPEAN JOURNAL OF NUTRITION LA English DT Article DE Multivitamin; Cross-sectional; Cohort; Diet ID FOOD FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY; RANDOMIZED CONTROLLED-TRIAL; DIETARY-SUPPLEMENT USERS; CARDIOVASCULAR-DISEASE; NATIONAL-HEALTH; BETA-CAROTENE; CANCER; ADULTS; PREVENTION AB The aim of this study was to examine the prevalence of self-reported multivitamin use in the Physicians' Health Study (PHS) cohort and its association with various lifestyle, clinical, and dietary factors to improve our understanding of who tends to use multivitamins. Among 18,040 middle-aged and older men, information on lifestyle and clinical factors was collected from a baseline enrollment questionnaire, and supplement use and dietary factors were assessed through a food-frequency questionnaire. Four categories of multivitamin use were considered: (1) no supplement use, (2) use of multivitamins only, (3) use of multivitamins with other individual vitamin/mineral supplements, and (4) use of other supplements only. We used logistic regression to calculate multivariate odds ratios and 95 % confidence intervals of taking multivitamin supplements for various lifestyle, clinical and dietary factors. Overall, 36 % of men reported current multivitamin use. Men who were older, current smokers, and currently using aspirin were 143, 43, and 74 % more likely to use multivitamins only. Men having a history of hypercholesterolemia were 16 % more likely to use multivitamins only. A 14, 24, and 26 % greater likelihood of using multivitamins was also observed among men consuming more fruits and vegetables, whole grains, and tea, respectively. Similar associations were observed for the likelihood of using multivitamins with other supplements; however, men with higher physical activity, history of cancer, hypertension, higher consumption of nuts, and lower consumption of red meat and coffee were also more likely to use multivitamins with other supplements (all P < 0.05). Self-reported multivitamin use associated with lifestyle, clinical and dietary factors may be an indicator of healthy behaviors. These results provide important information for the interpretation of the recent findings from the PHS II trial and consideration of results from observational studies of multivitamin use and chronic disease. C1 [Rautiainen, Susanne; Wang, Lu; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. [Rautiainen, Susanne; Wang, Lu; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Rautiainen, Susanne] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. [Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Rautiainen, S (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave,3rd Floor, Boston, MA 02215 USA. EM susanne.rautiainen@ki.se FU National Institutes of Health (Bethesda, MD, USA) [CA 097193, CA 34944, CA 40360, HL 26490, HL 34595]; Swedish Research Council for Health, Working Life, and Welfare (FORTE) Fellowship FX This work is supported by CA 097193, CA 34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of Health (Bethesda, MD, USA) as well as a Swedish Research Council for Health, Working Life, and Welfare (FORTE) Fellowship. NR 24 TC 4 Z9 4 U1 3 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1436-6207 EI 1436-6215 J9 EUR J NUTR JI Eur. J. Nutr. PD JUN PY 2014 VL 53 IS 4 BP 1065 EP 1072 DI 10.1007/s00394-013-0608-5 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AI3YL UT WOS:000336801700006 PM 24170064 ER PT J AU Hoganson, DM Bassett, EK Vacanti, JP AF Hoganson, David M. Bassett, Erik K. Vacanti, Joseph P. TI Lung tissue engineering SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Article DE Tissue Engineering; Scaffold; Decellularize; Biomimetic; Vascular Network; Trachea; Review ID ERYTHROCYTE/HEMOGLOBIN SOLUTION MIXTURES; MICROCHANNEL TECHNOLOGIES; ARTIFICIAL LUNGS; OXYGEN-TRANSPORT; RECTANGULAR CHANNELS; INITIAL-EXPERIENCE; BLOOD-VESSELS; STEM-CELLS; TRANSPLANTATION; DESIGN AB Lung tissue engineering is an emerging field focused on the development of lung replacement devices and tissue to treat patients with end stage lung disease. Microfluidic based lung assist devices have been developed that have biomimetically designed vascular networks that achieve physiologic blood flow. Gas exchange in these devices occurs across a thin respiratory membrane. Designed for intrathoracic implantation as a bridge to transplant or destination therapy, these lung assist devices will allow ambulation and hospital discharge for patients with end stage lung disease. Decellularized lungs subsequently recellularized with epithelial and endothelial cells have been implanted in small animal models with demonstration of initial gas exchange. Further development of these tissues and scaling to large animal models will validate this approach and may be an organ source for lung transplantation. Initial clinical success has been achieved with decellularized tracheal implants using autologous stem cells. Development of microfluidic lung models using similar architecture to the lung assist device technology allows study of lung biology and diseases with manipulation of lung cells and respiratory membrane strain. C1 [Hoganson, David M.; Bassett, Erik K.; Vacanti, Joseph P.] Massachusetts Gen Hosp, Dept Surg, Ctr Regenerat Med, Boston, MA 02114 USA. [Hoganson, David M.] Washington Univ, Dept Surg, St Louis, MO USA. RP Vacanti, JP (reprint author), Dept Pediat Surg, 55 Fruit St,Warren 1151, Boston, MA 02114 USA. EM jvacanti@partners.org FU NIH [F32 DK076349-01] FX The authors gratefully acknowledge support from the NIH (F32 DK076349-01, DMH). NR 43 TC 3 Z9 4 U1 2 U2 15 PU FRONTIERS IN BIOSCIENCE INC PI IRVINE PA 16471 SCIENTIFIC WAY, IRVINE, CA 92618 USA SN 1093-9946 EI 1093-4715 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD JUN 1 PY 2014 VL 19 BP 1227 EP 1239 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AI0WA UT WOS:000336569800003 PM 24896347 ER PT J AU Suter, MJ Gora, MJ Lauwers, GY Arnason, T Sauk, J Gallagher, KA Kava, L Tan, KM Soomro, AR Gallagher, TP Gardecki, JA Bouma, BE Rosenberg, M Nishioka, NS Tearney, GJ AF Suter, Melissa J. Gora, Michalina J. Lauwers, Gregory Y. Arnason, Thomas Sauk, Jenny Gallagher, Kevin A. Kava, Lauren Tan, Khay M. Soomro, Amna R. Gallagher, Timothy P. Gardecki, Joseph A. Bouma, Brett E. Rosenberg, Mireille Nishioka, Norman S. Tearney, Guillermo J. TI Esophageal-guided biopsy with volumetric laser endomicroscopy and laser cautery marking: a pilot clinical study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; BARRETTS-ESOPHAGUS; IN-VIVO; INTESTINAL METAPLASIA; SURVEILLANCE; MICROSCOPY; ENDOSCOPY; DYSPLASIA; CANCER AB Background: Biopsy surveillance protocols for the assessment of Barrett's esophagus can be subject to sampling errors, resulting in diagnostic uncertainty. Optical coherence tomography is a cross-sectional imaging technique that can be used to conduct volumetric laser endomicroscopy (VLE) of the entire distal esophagus. We have developed a biopsy guidance platform that places endoscopically visible marks at VLE-determined biopsy sites. Objective: The objective of this study was to demonstrate in human participants the safety and feasibility of VLE-guided biopsy in vivo. Design: A pilot feasibility study. Setting: Massachusetts General Hospital. Patients: A total of 22 participants were enrolled from January 2011 to June 2012 with a prior diagnosis of Barrett's esophagus. Twelve participants were used to optimize the laser marking parameters and the system platform. A total of 30 target sites were selected and marked in real-time by using the VLE-guided biopsy platform in the remaining 10 participants. Intervention: Volumetric laser endomicroscopy. Main Outcome Measurements: Endoscopic and VLE visibility, and accuracy of VLE diagnosis of the tissue between the laser cautery marks. Results: There were no adverse events of VLE and laser marking. The optimal laser marking parameters were determined to be 2 seconds at 410 mW, with a mark separation of 6 mm. All marks made with these parameters were visible on endoscopy and VLE. The accuracies for diagnosing tissue in between the laser cautery marks by independent blinded readers for endoscopy were 67% (95% confidence interval [CI], 47%-83%), for VLE intent-to-biopsy images 93% (95% CI, 78%-99%), and for corrected VLE post-marking images 100% when compared with histopathology interpretations. Limitations: This is a single-center feasibility study with a limited number of patients. Conclusion: Our results demonstrate that VLE-guided biopsy of the esophagus is safe and can be used to guide biopsy site selection based on the acquired volumetric optical coherence tomography imaging data. (Clinical trial registration number: NCT01439633.) C1 [Suter, Melissa J.; Tan, Khay M.] Massachusetts Gen Hosp, Pulmonol & Crit Care Unit, Boston, MA 02114 USA. [Suter, Melissa J.; Gora, Michalina J.; Gallagher, Kevin A.; Kava, Lauren; Soomro, Amna R.; Gallagher, Timothy P.; Gardecki, Joseph A.; Bouma, Brett E.; Rosenberg, Mireille; Nishioka, Norman S.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lauwers, Gregory Y.; Arnason, Thomas; Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Sauk, Jenny; Nishioka, Norman S.] Massachusetts Gen Hosp, Gastrointestinal Endoscopy Unit, Boston, MA 02114 USA. [Bouma, Brett E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bouma, Brett E.; Tearney, Guillermo J.] Harvard MIT Hlth Sci & Technol, Cambridge, MA USA. RP Tearney, GJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Fruit St,BHX604A, Boston, MA 02114 USA. EM gtearney@partners.org FU National Institutes of Health [R01DK091923, R01CA103769, R21CA141884, R00CA134920]; NinePoint Medical FX Study data were collected and managed with REDCap electronic data capture tools hosted at Massachusetts General Hospital. Funding was provided by grants from the National Institutes of Health R01DK091923 (G.K.T.), R01CA103769 (G.J.T.), R21CA141884 (G.J.T.), and R00CA134920 (M.J.S.). Massachusetts General Hospital has a licensing arrangement with NinePoint Medical. M. Suter, B. Bouma, N. Nishioka, and G. Tearney have the rights to receive royalties from this licensing arrangement. G. Tearney, N. Nishioka, and B. Bouma consult for NinePoint Medical, and M. Suter, B. Bouma, and G. Tearney receive sponsored research funding from NinePoint Medical. All other authors disclosed no financial relationships relevant to this publication. NR 22 TC 27 Z9 28 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUN PY 2014 VL 79 IS 6 BP 886 EP 896 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH9XD UT WOS:000336497700002 PM 24462171 ER PT J AU Attanasio, C Nord, AS Zhu, YW Blow, MJ Biddie, SC Mendenhall, EM Dixon, J Wright, C Hosseini, R Akiyama, JA Holt, A Plajzer-Frick, I Shoukry, M Afzal, V Ren, B Bernstein, BE Rubin, EM Visel, A Pennacchio, LA AF Attanasio, Catia Nord, Alex S. Zhu, Yiwen Blow, Matthew J. Biddie, Simon C. Mendenhall, Eric M. Dixon, Jesse Wright, Crystal Hosseini, Roya Akiyama, Jennifer A. Holt, Amy Plajzer-Frick, Ingrid Shoukry, Malak Afzal, Veena Ren, Bing Bernstein, Bradley E. Rubin, Edward M. Visel, Axel Pennacchio, Len A. TI Tissue-specific SMARCA4 binding at active and repressed regulatory elements during embryogenesis SO GENOME RESEARCH LA English DT Article ID CHROMATIN-REMODELING COMPLEX; EMBRYONIC STEM-CELLS; MUSCLE DEVELOPMENT; SWI/SNF COMPLEXES; SELF-RENEWAL; BRG1; ENHANCERS; GENOME; TRANSCRIPTION; EXPRESSION AB The SMARCA4 (also known as BRG1 in humans) chromatin remodeling factor is critical for establishing lineage-specific chromatin states during early mammalian development. However, the role of SMARCA4 in tissue-specific gene regulation during embryogenesis remains poorly defined. To investigate the genome-wide binding landscape of SMARCA4 in differentiating tissues, we engineered a Smarca4 FLAG knock-in mouse line. Using ChIP-seq, we identified similar to 51,000 SMARCA4associated regions across six embryonic mouse tissues (forebrain, hindbrain, neural tube, heart, limb, and face) at midgestation (E11.5). The majority of these regions was distal from promoters and showed dynamic occupancy, with most distal SMARCA4 sites (73%) confined to a single or limited subset of tissues. To further characterize these regions, we profiled active and repressive histone marks in the same tissues and examined the intersection of informative chromatin states and SMARCA4 binding. This revealed distinct classes of distal SMARCA4-associated elements characterized by activating and repressive chromatin signatures that were associated with tissue-specific up-or down-regulation of gene expression and relevant active/repressed biological pathways. We further demonstrate the predicted active regulatory properties of SMARCA4associated elements by retrospective analysis of tissue-specific enhancers and direct testing of SMARCA4-bound regions in transgenic mouse assays. Our results indicate a dual active/repressive function of SMARCA4 at distal regulatory sequences in vivo and support its role in tissue-specific gene regulation during embryonic development. C1 [Attanasio, Catia; Nord, Alex S.; Zhu, Yiwen; Hosseini, Roya; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Afzal, Veena; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA. [Blow, Matthew J.; Biddie, Simon C.; Wright, Crystal; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA. [Biddie, Simon C.] Cambridge Univ NHS Trust, Addenbrookes Hosp, Cambridge CB2 0QQ, England. [Mendenhall, Eric M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, HHMI, Boston, MA 02114 USA. [Mendenhall, Eric M.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mendenhall, Eric M.; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Dixon, Jesse; Ren, Bing] UCSD Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. RP Pennacchio, LA (reprint author), Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Genom Div, Berkeley, CA 94720 USA. EM lapennacchio@lbl.gov RI Blow, Matthew/G-6369-2012; Visel, Axel/A-9398-2009; attanasio, catia/D-5042-2017; OI Blow, Matthew/0000-0002-8844-9149; Visel, Axel/0000-0002-4130-7784; Biddie, Simon/0000-0002-8253-0253; Mendenhall, Eric/0000-0002-7395-6295 FU National Human Genome Research Institute [HG003988, U54HG006997]; Swiss National Science Foundation (SNSF) Advanced Researcher fellowship; NIH/NIGMS NRSA F32 [GM105202]; University of California [DE-AC02-05CH11231] FX L.A.P. and A.V. were supported by grants HG003988 and U54HG006997 funded by the National Human Genome Research Institute. C.A. was supported by the Swiss National Science Foundation (SNSF) Advanced Researcher fellowship. A.S.N. was supported by NIH/NIGMS NRSA F32 fellowship GM105202. Research was conducted at the E.O. Lawrence Berkeley National Laboratory and performed under Department of Energy Contract DE-AC02-05CH11231, University of California. NR 52 TC 19 Z9 19 U1 0 U2 10 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 JUN PY 2014 VL 24 IS 6 BP 920 EP 929 DI 10.1101/gr.168930.113 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA AI2BQ UT WOS:000336662200004 PM 24752179 ER PT J AU Steinberg, BA Hellkamp, AS Lokhnygina, Y Halperin, JL Breithardt, G Passman, R Hankey, GJ Patel, MR Becker, RC Singer, DE Hacke, W Berkowitz, SD Nessel, CC Mahaffey, KW Fox, KAA Califf, RM Piccini, JP AF Steinberg, Benjamin A. Hellkamp, Anne S. Lokhnygina, Yuliya Halperin, Jonathan L. Breithardt, Gunter Passman, Rod Hankey, Graeme J. Patel, Manesh R. Becker, Richard C. Singer, Daniel E. Hacke, Werner Berkowitz, Scott D. Nessel, Christopher C. Mahaffey, Kenneth W. Fox, Keith A. A. Califf, Robert M. Piccini, Jonathan P. CA ROCKET AF Steering Comm & Investig TI Use and outcomes of antiarrhythmic therapy in patients with atrial fibrillation receiving oral anticoagulation: Results from the ROCKET AF trial SO HEART RHYTHM LA English DT Article DE Atrial fibrillation; Antiarrhythmic drugs; Rivaroxaban; Warfarin; Outcomes ID WARFARIN; RIVAROXABAN; PREDICTION; AMIODARONE; EVENTS AB BACKGROUND Antiarrhythmic drugs (AADs) and anticoagulation are mainstays of atrial fibrillation (AF) treatment. OBJECTIVE To study the use and outcomes of AAD therapy in anticoagulated patients with AF. METHODS Patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial (N = 14,264) were stratified by AAD use at baseline: amiodarone, other AAD, or no AAD. Multivariable adjustment was performed to compare stroke, bleeding, and death across AAD groups as well as across treatment assignment (rivaroxaban or warfarin). RESULTS Of 14,264 patients randomized, 1681 (11.8%) were treated with an AAD (1144 [8%] with amiodarone and 537 [3.8%] with other AADs). Amiodarone-treated patients were Less often female (38% vs 48%), had more persistent AF (64% vs 40%), and more concomitant heart failure (71% vs 41%) than were patients receiving other AADs. Patients receiving no AAD more closely resembled amiodarone-treated patients. Time in therapeutic range was significantly Lower in warfarin-treated patients receiving amiodarone than in those receiving no AAD (50% vs 58%; P < .0001). Compared with no AAD, neither amiodarone (adjusted hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.74-1.31; P = .9) nor other AADs (adjusted HR 0.66; 95% CI 0.37-1.17; P = .15) were associated with increased mortality. Similar results were observed for embolic and bleeding outcomes. Treatment effects of rivaroxaban vs warfarin in patients receiving no AAD were consistent with results from the overall trial (primary end point: adjusted HR 0.82; 95% CI 0.68-0.98; P-interaction = .06; safety end point: adjusted HR 1.12; 95% CI 0.90-1.24; P-inteiaction = .33). CONCLUSION Treatment with AADs was not associated with increased morbidity or mortality in anticoagulated patients with AF. The effect of amiodarone on outcomes in patients receiving rivaroxaban requires further investigation. C1 [Steinberg, Benjamin A.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27715 USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. [Breithardt, Gunter] Hosp Univ Munster, Dept Cardiovasc Med, Munster, Germany. [Passman, Rod] Northwestern Univ Feinberg, Sch Med, Chicago, IL USA. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia. [Becker, Richard C.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Montville, NJ USA. [Nessel, Christopher C.] Janssen Res & Development LLC, Raritan, NJ USA. [Mahaffey, Kenneth W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Medi Inst, Durham, NC USA. RP Steinberg, BA (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM benjamin.steinberg@dm.duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Janssen Research & Development LLC, Raritan, NJ; Bayer Health Care AG, Leverkusen, Germany; NTH T-32 training grant [5 T32 HL 7101-38, R34 HL113404-01]; Boehringer Ingelheim; Bristol-Myers Squibb; Pfizer; Sanofi-Aventis; Johnson Johnson; Medtronic; Ortho-McNeil-Janssen Pharmaceuticals; Bayer Health Care; Genzyme; Bayer; AstraZeneca; Daiichi Sankyo; Eli Lilly; GlaxoSmithKline; Merck; Momenta Pharmaceuticals; Novartis; Porto la; Pozen; Regado Biotechnologies; Medicines Company; Ortho/McNeill; Polymedix; ARCA Biopharma; Boston Scientific; GE Healthcare; ResMed; BMS/Pfizer; Forest Laboratories; Spectranetics FX This work was supported by Janssen Research & Development LLC, Raritan, NJ, and Bayer Health Care AG, Leverkusen, Germany.; Dr Steinberg was funded by NTH T-32 training grant #5 T32 HL 7101-38 However, no relationships exist related to the analysis presented. Dr Halperin has received honoraria and served as a consultant and is on an advisory board for Bayer and Johnson & Johnson. Dr Brcithardt has received honoraria from Johnson & Johnson and Bayer and advisory board fees from Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis. Dr Passman has received speaker's bureau fees from Boehringer ingelheim, Johnson & Johnson, and Medtronic and research support from Medtronic; he is also funded by the NIH R34 HL113404-01. Dr Hankcy has received honoraria for serving on executive committees for Johnson & Johnson and Bayer. Dr Patel has received honoraria from Johnson & Johnson and Bayer Health Care for serving on the executive committee of the ROCKET AF trial; consulting fees from Ortho-McNeil-Janssen Pharmaceuticals and Bayer Health Care; and advisory board fees from Genzyme. Dr Becker has received research support from Bayer and Johnson & johnson. Dr Singer is a consultant and member of a scientific advisory hoard for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson &. Johnson, and Pfizer; has an institutional research support contract with Johnson & Johnson; and served as an unpaid ROCKET AF executive committee member. Dr Hacke has received honoraria for serving on executive committees for Johnson & Johnson and Bayer. Dr Berkowitz is a full-time employee of Bayer Health Care Pharmaceuticals. Dr Nessel is a full-time employee of Janssen Research & Development LLC. Dr Mahaffey has received grant support (significant) from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck, Momenta Pharmaceuticals, Novartis, Porto la, Pozen, Regado Biotechnologies, Sanofi-Aventis, Schering-Plough (now Merck), and The Medicines Company; he has also received consulting fees (significant) from AstraZeneca and Johnson & Johnson, (modest) Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Ortho/McNeill, Pfizer, Polymedix, Sanofi-Aventis, and Schering-Plough (now Merck). Dr Fox has received grant funding and honoraria from Bayer and Johnson & Johnson. Dr Califf has received consulting fees and research funding from Johnson & Johnson; all other industry interactions are listed at www.dcri.org/about-us/conflict-of-interest. Dr Piccini has received grants for clinical research from ARCA Biopharma, Boston Scientific, GE Healthcare, Johnson & Johnson, and ResMed; he has also received consulting fees from BMS/Pfizer, Johnson & Johnson, Forest Laboratories, Medtronic, and Spectranetics. NR 15 TC 12 Z9 13 U1 1 U2 4 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 JUN PY 2014 VL 11 IS 6 BP 925 EP 932 DI 10.1016/j.hrthm.2014.03.006 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH8NU UT WOS:000336395600003 PM 24833235 ER PT J AU Macri, V Mahida, SN Zhang, ML Sinner, MF Dolmatova, EV Tucker, NR McLellan, M Shea, MA Milan, DJ Lunetta, KL Benjamin, EJ Ellinor, PT AF Macri, Vincenzo Mahida, Saagar N. Zhang, Michael L. Sinner, Moritz F. Dolmatova, Elena V. Tucker, Nathan R. McLellan, Micheal Shea, Marisa A. Milan, David J. Lunetta, Kathryn L. Benjamin, Emelia J. Ellinor, Patrick T. TI A novel trafficking-defective HCN4 mutation is associated with early-onset atrial fibrillation SO HEART RHYTHM LA English DT Article DE HCN4; Mutation; Atrial fibrillation; Electrophysiology ID FUNCTIONAL EXPRESSION; SINUS BRADYCARDIA; PACEMAKER CHANNEL; DOMAIN; HAPLOINSUFFICIENCY; DYSFUNCTION; TERMINUS; GENES AB BACKGROUND Atrial fibrillation (AF) is the most common arrhythmia, and a recent genome-wide association study identified the hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) as a novel AF susceptibility locus. HCN4 encodes for the cardiac pacemaker channel, and HCN4 mutations are associated with familial sinus bradycardia and AF. OBJECTIVE The purpose of this study was to determine whether novel variants in the coding region of HCN4 contribute to the susceptibility for AF. METHODS We sequenced the coding region of HCN4 for novel variants from 527 cases with early-onset AF from the Massachusetts General Hospital AF Study and 443 referents from the Framingham Heart Study. We used site-directed mutagenesis, cellular electrophysiology, immunocytochemistry, and confocal microscopy to functionally characterize novel variants. RESULTS We found the frequency of novel coding HCN4 variants was 2-fold greater for individuals with AF (7 variants) compared to the referents (3 variants). We determined that of the 7 novel HCN4 variants in our AF cases, 1 (p.Pro257Ser, located in the amino-terminus adjacent to the first transmembrane spanning domain) did not traffic to cell membrane, whereas the remaining 6 were not functionally different from wild type. In addition, the 3 novel variants in our referents did not alter function compared to wild-type. Coexpression studies showed that the p.Pro257Ser mutant channel failed to colocalize with the wild-type HCN4 channel on the cell membrane. CONCLUSION Our findings are consistent with HCN4 haploinsufficiency as the likely mechanism for early-onset AF in the p. Pro257Ser carrier. C1 [Macri, Vincenzo; Mahida, Saagar N.; Zhang, Michael L.; Sinner, Moritz F.; Dolmatova, Elena V.; Tucker, Nathan R.; McLellan, Micheal; Milan, David J.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Macri, Vincenzo; Mahida, Saagar N.; Dolmatova, Elena V.; Tucker, Nathan R.; Milan, David J.; Ellinor, Patrick T.] Harvard Univ, Sch Med, Boston, MA USA. [Sinner, Moritz F.] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Sinner, Moritz F.; Lunetta, Kathryn L.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Shea, Marisa A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. RP Ellinor, PT (reprint author), Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM ellinor@mgh.harvard.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health [1RO1HL104156, 1K2411L105780, 1RO1HL092577]; Established Investigator Award from the American Heart Association [13EIA14220013]; National Heart, Lung, and Blood Institute [T32HL007208]; Heart Rhythm Society (The Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology) FX Drs. Macri and Mahida contributed equally to this manuscript. The current work was funded by National Institutes of Health Grants 1RO1HL104156 and 1K2411L105780 to Dr. Elinor and Grant 1RO1HL092577 to Drs. Benjamin and Elinor. Dr. Ellinor is supported by an Established Investigator Award from the American Heart Association (13EIA14220013). Dr. Tucker was supported by award number T32HL007208 from the National Heart, Lung, and Blood Institute. Dr. Macri is supported by the Heart Rhythm Society (The Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology). NR 25 TC 9 Z9 9 U1 0 U2 7 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 JUN PY 2014 VL 11 IS 6 BP 1055 EP 1062 DI 10.1016/j.hrthm.2014.03.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH8NU UT WOS:000336395600021 PM 24607718 ER PT J AU Tsunemi, T Krainc, D AF Tsunemi, Taiji Krainc, Dimitri TI Zn2+ dyshomeostasis caused by loss of ATP13A2/PARK9 leads to lysosomal dysfunction and alpha-synuclein accumulation SO HUMAN MOLECULAR GENETICS LA English DT Article ID P-TYPE ATPASE; MAMMALIAN ZINC TRANSPORTERS; KUFOR-RAKEB SYNDROME; PARKINSONS-DISEASE; NEURODEGENERATIVE DISEASES; CONFERS RESISTANCE; INTESTINAL-CELLS; HOMEOSTASIS; EXPRESSION; PROTEINS AB Mutations in ATP13A2 (PARK9) cause Kufor-Rakeb syndrome (KRS) characterized by juvenile-onset parkinsonism, pyramidal signs and dementia. PARK9 belongs to type 5 P-type ATPase with its putative function as a cation transporter. Loss of PARK9 leads to lysosomal dysfunction and subsequent alpha-synuclein (alpha-Syn) accumulation. However, the mechanistic link between PARK9 and lysosomal dysfunction remains unclear. Here, we found that patient fibroblasts expressing mutant PARK9 or primary neurons with silenced PARK9 exhibited increased sensitivity to extracellular zinc (Zn2+). This effect was rescued with the Zn2+ chelators clioquinol or TPEN. PARK9-deficient cells showed decreased lysosomal sequestration of Zn2+ and increased expression of zinc transporters. Importantly, increased concentrations of Zn2+ (Zn2+ stress) resulted in lysosomal dysfunction that was partially restored by expression of wild-type PARK9. Zn2+ stress also caused increased expression of alpha-Syn and consequently decreased activity of the lysosomal enzyme glucocerebrosidase. Together, these data suggest that PARK9 loss of function leads to dyshomeostasis of intracellular Zn2+ that in turn contributes to lysosomal dysfunction and accumulation of alpha-Syn. It will be of interest to examine whether therapeutic lowering of zinc may prove beneficial for patients with KRS. C1 [Tsunemi, Taiji; Krainc, Dimitri] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA. RP Krainc, D (reprint author), MassGen Inst Neurodegenerat Dis, 114 16th St,Room 2008, Charlestown, MA 02129 USA. EM krainc@helix.mgh.harvard.edu FU National Institute of Health [R01NS076054] FX This work was supported by National Institute of Health (R01NS076054 to D.K.). NR 57 TC 39 Z9 41 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2014 VL 23 IS 11 BP 2791 EP 2801 DI 10.1093/hmg/ddt572 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AH9ST UT WOS:000336483200001 PM 24334770 ER PT J AU Moayyeri, A Hsu, YH Karasik, D Estrada, K Xiao, SM Nielson, C Srikanth, P Giroux, S Wilson, SG Zheng, HF Smith, AV Pye, SR Leo, PJ Teumer, A Hwang, JY Ohlsson, C McGuigan, F Minster, RL Hayward, C Olmos, JM Lyytikainen, LP Lewis, JR Swart, KMA Masi, L Oldmeadow, C Holliday, EG Cheng, SL van Schoor, NM Harvey, NC Kruk, M Fabiola Del Greco, M Igl, W Trummer, O Grigoriou, E Luben, R Liu, CT Zhou, YH Oei, L Medina-Gomez, C Zmuda, J Tranah, G Brown, SJ Williams, FM Soranzo, N Jakobsdottir, J Siggeirsdottir, K Holliday, KL Hannemann, A Go, MJ Garcia, M Polasek, O Laaksonen, M Zhu, K Enneman, AW McEvoy, M Peel, R Sham, PC Jaworski, M Johansson, A Hicks, AA Pludowski, P Scott, R Dhonukshe-Rutten, RAM van der Velde, N Kahonen, M Viikari, JS Sievanen, H Raitakari, OT Gonzalez-Macias, J Hernandez, JL Mellstroom, D Ljunggren, O Cho, YS Volker, U Nauck, M Homuth, G Volzke, H Haring, R Brown, MA McCloskey, E Nicholson, GC Eastell, R Eisman, JA Jones, G Reid, IR Dennison, EM Wark, J Boonen, S Vanderschueren, D Wu, FCW Aspelund, T Richards, JB Bauer, D Hofman, A Khaw, KT Dedoussis, G Obermayer-Pietsch, B Gyllensten, U Pramstaller, PP Lorenc, RS Cooper, C Kung, AWC Lips, P Alen, M Attia, J Brandi, ML de Groot, LCPGM Lehtimaki, T Riancho, JA Campbell, H Liu, YM Harris, TB Akesson, K Karlsson, M Lee, JY Wallaschofski, H Duncan, EL O'Neill, TW Gudnason, V Spector, TD Rousseau, F Orwoll, E Cummings, SR Wareham, NJ Rivadeneira, F Uitterlinden, AG Prince, RL Kiel, DP Reeve, J Kaptoge, SK AF Moayyeri, Alireza Hsu, Yi-Hsiang Karasik, David Estrada, Karol Xiao, Su-Mei Nielson, Carrie Srikanth, Priya Giroux, Sylvie Wilson, Scott G. Zheng, Hou-Feng Smith, Albert V. Pye, Stephen R. Leo, Paul J. Teumer, Alexander Hwang, Joo-Yeon Ohlsson, Claes McGuigan, Fiona Minster, Ryan L. Hayward, Caroline Olmos, Jose M. Lyytikaeinen, Leo-Pekka Lewis, Joshua R. Swart, Karin M. A. Masi, Laura Oldmeadow, Chris Holliday, Elizabeth G. Cheng, Sulin van Schoor, Natasja M. Harvey, Nicholas C. Kruk, Marcin Fabiola Del Greco, M. Igl, Wilmar Trummer, Olivia Grigoriou, Efi Luben, Robert Liu, Ching-Ti Zhou, Yanhua Oei, Ling Medina-Gomez, Carolina Zmuda, Joseph Tranah, Greg Brown, Suzanne J. Williams, Frances M. Soranzo, Nicole Jakobsdottir, Johanna Siggeirsdottir, Kristin Holliday, Kate L. Hannemann, Anke Go, Min Jin Garcia, Melissa Polasek, Ozren Laaksonen, Marika Zhu, Kun Enneman, Anke W. McEvoy, Mark Peel, Roseanne Sham, Pak Chung Jaworski, Maciej Johansson, Asa Hicks, Andrew A. Pludowski, Pawel Scott, Rodney Dhonukshe-Rutten, Rosalie A. M. van der Velde, Nathalie Kaehoenen, Mika Viikari, Jorma S. Sievaenen, Harri Raitakari, Olli T. Gonzalez-Macias, Jesus Hernandez, Jose L. Mellstroem, Dan Ljunggren, Oesten Cho, Yoon Shin Voelker, Uwe Nauck, Matthias Homuth, Georg Voelzke, Henry Haring, Robin Brown, Matthew A. McCloskey, Eugene Nicholson, Geoffrey C. Eastell, Richard Eisman, John A. Jones, Graeme Reid, Ian R. Dennison, Elaine M. Wark, John Boonen, Steven Vanderschueren, Dirk Wu, Frederick C. W. Aspelund, Thor Richards, J. Brent Bauer, Doug Hofman, Albert Khaw, Kay-Tee Dedoussis, George Obermayer-Pietsch, Barbara Gyllensten, Ulf Pramstaller, Peter P. Lorenc, Roman S. Cooper, Cyrus Kung, Annie Wai Chee Lips, Paul Alen, Markku Attia, John Luisa Brandi, Maria de Groot, Lisette C. P. G. M. Lehtimaeki, Terho Riancho, Jose A. Campbell, Harry Liu, Yongmei Harris, Tamara B. Akesson, Kristina Karlsson, Magnus Lee, Jong-Young Wallaschofski, Henri Duncan, Emma L. O'Neill, Terence W. Gudnason, Vilmundur Spector, Timothy D. Rousseau, Francois Orwoll, Eric Cummings, Steven R. Wareham, Nick J. Rivadeneira, Fernando Uitterlinden, Andre G. Prince, Richard L. Kiel, Douglas P. Reeve, Jonathan Kaptoge, Stephen K. TI Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium SO HUMAN MOLECULAR GENETICS LA English DT Article ID X-RAY ABSORPTIOMETRY; QUANTITATIVE ULTRASOUND; MINERAL DENSITY; OSTEOPOROSIS; FRACTURE; RISK; DENSITOMETRY; PHENOTYPES; CALCANEUS; WOMEN AB Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology. C1 [Moayyeri, Alireza; Luben, Robert; Khaw, Kay-Tee; Reeve, Jonathan; Kaptoge, Stephen K.] Univ Cambridge, Dept Publ Hlth Primary Care, Cambridge CB1 8RN, England. [Moayyeri, Alireza; Wilson, Scott G.; Williams, Frances M.; Richards, J. Brent; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Hebrew SeniorLife, Inst Aging Res, Boston, MA USA. [Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Hsu, Yi-Hsiang; Karasik, David; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA. [Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Enneman, Anke W.; van der Velde, Nathalie; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Estrada, Karol] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Analyt & Translat Genet Unit,Dept Med, Boston, MA USA. [Estrada, Karol] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Estrada, Karol; Oei, Ling; Medina-Gomez, Carolina; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Netherlands Consortium Healthy Aging NCHA, Netherlands Genom Initiat NGI, Leiden, Netherlands. [Xiao, Su-Mei; Kung, Annie Wai Chee] Univ Hong Kong, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Xiao, Su-Mei; Kung, Annie Wai Chee] Univ Hong Kong, Res Ctr Heart Brain Hormone & Healthy Aging, Hong Kong, Hong Kong, Peoples R China. [Sham, Pak Chung] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Sham, Pak Chung] Univ Hong Kong, Ctr Reprod Dev & Growth, Hong Kong, Hong Kong, Peoples R China. [Nielson, Carrie; Srikanth, Priya] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Orwoll, Eric] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. [Giroux, Sylvie; Rousseau, Francois] HSFA, Ctr Rech CHU Quebec, Quebec City, PQ, Canada. [Wilson, Scott G.; Lewis, Joshua R.; Zhu, Kun; Prince, Richard L.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Wilson, Scott G.; Lewis, Joshua R.; Brown, Suzanne J.; Zhu, Kun; Prince, Richard L.] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA 6000, Australia. [Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Med, Montreal, PQ, Canada. [Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Human Genet, Montreal, PQ, Canada. [Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Epidemiol, Montreal, PQ, Canada. [Zheng, Hou-Feng; Richards, J. Brent] McGill Univ, Lady Davis Inst, Dept Biostat, Montreal, PQ, Canada. [Smith, Albert V.; Jakobsdottir, Johanna; Siggeirsdottir, Kristin; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Siggeirsdottir, Kristin; Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Pye, Stephen R.; Holliday, Kate L.; O'Neill, Terence W.] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester M13 9WL, Lancs, England. [Wu, Frederick C. W.] Univ Manchester, Manchester Royal Infirm, Manchester Acad Hlth Sci Ctr, Androl Res Unit,Dev & Regenerat Biomed Res Grp, Manchester M13 9WL, Lancs, England. [Leo, Paul J.; Brown, Matthew A.; Duncan, Emma L.] Univ Queensland, Diamantina Inst, Human Genet Grp, Brisbane, Qld, Australia. [Teumer, Alexander; Voelker, Uwe; Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany. [Hannemann, Anke; Nauck, Matthias; Haring, Robin; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Clin Chem, Greifswald, Germany. [Hannemann, Anke; Nauck, Matthias; Haring, Robin; Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Lab Med, Greifswald, Germany. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Hwang, Joo-Yeon; Go, Min Jin; Lee, Jong-Young] NIH, Ctr Genome Sci, Chungcheongbuk, South Korea. [Ohlsson, Claes; Mellstroem, Dan] Univ Gothenburg, Ctr Bone & Arthrit Res, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden. [McGuigan, Fiona; Akesson, Kristina; Karlsson, Magnus] Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci, Malmo, Sweden. [Karlsson, Magnus] Lund Univ, Dept Orthopaed, Malmo, Sweden. [Minster, Ryan L.] Univ Pittsburgh, Dept Human Genet, Pitsburgh, PA USA. [Zmuda, Joseph] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pitsburgh, PA USA. [Hayward, Caroline] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Univ Cantabria, Dept Med, E-39005 Santander, Spain. [Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Hosp Univ Marques Valdecilla, Dept Internal Med, Santander, Spain. [Olmos, Jose M.; Gonzalez-Macias, Jesus; Hernandez, Jose L.; Riancho, Jose A.] Inst Formac & Invest Marques Valdecilla IFIMAV, Santander, Spain. [Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Fimlab Labs, Dept Clin Chem, Tampere, Finland. [Lyytikaeinen, Leo-Pekka; Lehtimaeki, Terho] Univ Tampere, Dept Clin Chem, Sch Med, FIN-33101 Tampere, Finland. [Kaehoenen, Mika] Univ Tampere, Dept Clin Physiol, Sch Med, FIN-33101 Tampere, Finland. [Swart, Karin M. A.; van Schoor, Natasja M.] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Lips, Paul] Vrije Univ Amsterdam, Med Ctr, Dept Endocrinol, Amsterdam, Netherlands. [Lips, Paul] Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Masi, Laura] Univ Florence, Metab Bone Dis Unit AOUC, Florence, Italy. [Luisa Brandi, Maria] Univ Florence, Dept Surg & Translat Med, Florence, Italy. [Oldmeadow, Chris; Holliday, Elizabeth G.; McEvoy, Mark; Peel, Roseanne; Scott, Rodney; Attia, John] Univ Newcastle, John Hunter Hosp, Newcastle, NSW 2300, Australia. [Oldmeadow, Chris; Holliday, Elizabeth G.; McEvoy, Mark; Peel, Roseanne; Scott, Rodney; Attia, John] Hunter Med Res Inst, Newcastle, NSW, Australia. [Cheng, Sulin] Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla, Finland. [Harvey, Nicholas C.; Dennison, Elaine M.; Cooper, Cyrus] Univ Southampton, MRC Lifecourse Epidemiol Unit, Southampton, Hants, England. [Kruk, Marcin; Jaworski, Maciej; Pludowski, Pawel; Lorenc, Roman S.] Childrens Mem Hlth Inst, Dept Biochem Radioimmunol & Expt Med, Warsaw, Poland. [Fabiola Del Greco, M.; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy. [Fabiola Del Greco, M.; Hicks, Andrew A.; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany. [Igl, Wilmar; Johansson, Asa; Gyllensten, Ulf] SciLifeLab, Rudbeck Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Ljunggren, Oesten] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Trummer, Olivia; Obermayer-Pietsch, Barbara] Med Univ Graz, Div Endocrinol & Metab, Dept Internal Med, Graz, Austria. [Grigoriou, Efi; Dedoussis, George] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece. [Liu, Ching-Ti; Zhou, Yanhua] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Tranah, Greg; Bauer, Doug; Cummings, Steven R.] Univ Calif San Francisco, San Francisco Coordinating Ctr, Calif Pacif Med Ctr Res Inst, San Francisco, CA 94143 USA. [Tranah, Greg; Bauer, Doug; Cummings, Steven R.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Soranzo, Nicole] Wellcome Trust Res Labs, Sanger Inst, Cambridge, England. [Garcia, Melissa; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA. [Polasek, Ozren] Univ Split, Sch Med, Dept Publ Hlth, Split, Croatia. [Laaksonen, Marika] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland. [Dhonukshe-Rutten, Rosalie A. M.; de Groot, Lisette C. P. G. M.] Wageningen Univ, Dept Human Nutr, NL-6700 AP Wageningen, Netherlands. [van der Velde, Nathalie] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Sect Geriatr, NL-1105 AZ Amsterdam, Netherlands. [Kaehoenen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Viikari, Jorma S.] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland. [Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland. [Viikari, Jorma S.] Univ Turku, Dept Med, Turku, Finland. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Sievaenen, Harri] UKK Inst Hlth Promot Res, Tampere, Finland. [Cho, Yoon Shin] Hallym Univ, Dept Biomed Sci, Chunchon, South Korea. [McCloskey, Eugene] Univ Sheffield, Natl Inst Hlth & Res NIHR, Musculoskeletal Biomed Res Unit, Sheffield, S Yorkshire, England. [McCloskey, Eugene; Eastell, Richard] Univ Sheffield, Acad Unit Bone Metab, Metab Bone Ctr, Sheffield, S Yorkshire, England. [Nicholson, Geoffrey C.] Univ Queensland, Rural Clin Sch, Toowoomba, Qld, Australia. [Eisman, John A.] Garvan Inst Med Res, Clin Translat & Adv Educ & Osteoporosis & Bone Bi, Sydney, NSW, Australia. [Eisman, John A.] Univ New S Wales, Dept ofMedicine, Kensington, NSW 2033, Australia. [Eisman, John A.] Univ Notre Dame, Sch Med Sydney, Sydney, NSW, Australia. [Eisman, John A.] St Vincents Hosp, Dept Endocrinol, Sydney, NSW 2010, Australia. [Jones, Graeme] Univ Tasmania, Menzies Res Inst, Hobart, Tas, Australia. [Reid, Ian R.] Univ Auckland, Auckland 1, New Zealand. [Wark, John] Royal Melbourne Hosp, Dept Clin Sci, Melbourne, Vic, Australia. [Boonen, Steven] Katholieke Univ Leuven, Div Geriatr Med, Leuven, Belgium. [Boonen, Steven] Katholieke Univ Leuven, Ctr Metab Bone Dis, Leuven, Belgium. [Vanderschueren, Dirk] Katholieke Univ Leuven, Dept Androl & Endocrinol, Leuven, Belgium. [Cooper, Cyrus; Reeve, Jonathan] Univ Oxford, NIHR Musculoskeletal Biomed Res Unit, Inst Musculoskeletal Sci, Oxford, England. [Alen, Markku] Oulu Univ Hosp, Dept Rehabil Med, Oulu, Finland. [Alen, Markku] Inst Hlth Sci, Oulu, Finland. [Campbell, Harry] Ctr Populat Hlth Sci, Sch Med, Edinburgh, Midlothian, Scotland. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC USA. [Duncan, Emma L.] Royal Brisbane & Womens Hosp, Dept Endocrinol, Brisbane, Qld, Australia. [Rousseau, Francois] Univ Laval, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ, Canada. [Rousseau, Francois] Univ Laval, APOGEE Net, CanGeneTest Network Genet Hlth Serv & Policy, Quebec City, PQ, Canada. [Wareham, Nick J.] Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Reeve, Jonathan; Kaptoge, Stephen K.] Strangeways Res Lab, Cambridge CB1 4RN, England. RP Kaptoge, SK (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge CB1 8RN, England. EM stephen@srl.cam.ac.uk RI Lyytikainen, Leo-Pekka/C-8544-2016; Oei, Ling/E-8163-2013; Smith, Albert/K-5150-2015; Pye, Stephen/D-9236-2011; Hayward, Caroline/M-8818-2016; Hicks, Andrew/E-9518-2017; Polasek, Ozren/B-6002-2011; Rivadeneira, Fernando/O-5385-2015; Duncan, Emma/L-1224-2013; Aspelund, Thor/C-5983-2008; Pramstaller, Peter/C-2357-2008; Nicholson, Geoffrey/F-1901-2010; Leo, Paul/B-3470-2011; Lewis, Joshua/D-5077-2013; Moayyeri, Alireza/N-3332-2014; Reeve, Jonathan/C-7551-2012; Gudnason, Vilmundur/K-6885-2015 OI Johansson, Asa/0000-0002-2915-4498; Brown, Matthew A/0000-0003-0538-8211; de Groot, Lisette /0000-0003-2778-2789; Luben, Robert/0000-0002-5088-6343; Soranzo, Nicole/0000-0003-1095-3852; Karasik, David/0000-0002-8826-0530; Medina-Gomez, Carolina/0000-0001-7999-5538; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Oei, Ling/0000-0003-3523-458X; Smith, Albert/0000-0003-1942-5845; Pye, Stephen/0000-0002-7263-2897; Hayward, Caroline/0000-0002-9405-9550; Hicks, Andrew/0000-0001-6320-0411; van der Velde, Nathalie/0000-0002-6477-6209; Kiel, Douglas/0000-0001-8474-0310; Williams, Frances/0000-0002-2998-2744; Polasek, Ozren/0000-0002-5765-1862; Rivadeneira, Fernando/0000-0001-9435-9441; Duncan, Emma/0000-0002-8143-4403; Aspelund, Thor/0000-0002-7998-5433; Nicholson, Geoffrey/0000-0002-0152-1153; Leo, Paul/0000-0001-8325-4134; Lewis, Joshua/0000-0003-1003-8443; Moayyeri, Alireza/0000-0002-9143-2161; Reeve, Jonathan/0000-0002-4364-2682; Gudnason, Vilmundur/0000-0001-5696-0084 FU European Commission [HEALTH-F2-2008-201865-GEFOS] FX This research and the Genetic Factors for Osteoporosis (GEFOS) consortium have been funded by the European Commission (HEALTH-F2-2008-201865-GEFOS). Several other sources of funding and people have supported work in the contributing cohorts as acknowledged in Supplementary Material, Table S2. NR 43 TC 27 Z9 28 U1 2 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 1 PY 2014 VL 23 IS 11 BP 3054 EP 3068 DI 10.1093/hmg/ddt675 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AH9ST UT WOS:000336483200021 PM 24430505 ER PT J AU Kamihara, J Rana, HQ Garber, JE AF Kamihara, Junne Rana, Huma Q. Garber, Judy E. TI Germline TP53 Mutations and the Changing Landscape of Li-Fraumeni Syndrome SO HUMAN MUTATION LA English DT Review DE TP53; p53; cancer; Li-Fraumeni syndrome; germline; screening; management; genetic counseling ID ADRENAL-CORTICAL CARCINOMA; ONSET BREAST-CANCER; SOFT-TISSUE-SARCOMA; P53 GENE; SOUTHERN BRAZIL; RELATIVE FREQUENCY; COLORECTAL-CANCER; FAMILIAL SYNDROME; PEDIATRIC CANCER; R337H MUTATION AB Since its description by Li and Fraumeni over 40 years ago, Li-Fraumeni syndrome (LFS) remains one of the most striking familial cancer predisposition syndromes. Children and adults are affected by a wide array of cancers that occur predominantly at younger ages. This review discusses LFS, describes its association with TP53, and examines the classic and evolving definitions of the syndrome. The potential implications of multigene assessments of individuals at increased cancer risk, which have already begun to identify those with very little personal or family cancer history carrying germline TP53 mutations, are considered. Newer options in the management of individuals with LFS are also discussed, highlighting the importance of further clinical trials for cancer detection, prevention, and management. Finally, we observe how the clinical criteria for TP53 mutation screening appear to be evolving as our understanding of the impact of germline TP53 mutations continues to expand. C1 [Kamihara, Junne] Harvard Univ, Sch Med, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA USA. [Kamihara, Junne] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA USA. [Rana, Huma Q.; Garber, Judy E.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM Judy_Garber@dfci.harvard.edu OI Rana, Huma/0000-0002-1598-6752 FU NCI NIH HHS [T32 CA136432] NR 85 TC 30 Z9 31 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD JUN PY 2014 VL 35 IS 6 SI SI BP 654 EP 662 DI 10.1002/humu.22559 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA AI1NX UT WOS:000336618900003 PM 24706533 ER PT J AU Cornejo, KM Hutchinson, L Deng, A Tomaszewicz, K Welch, M Lyle, S Dresser, K Cosar, EF AF Cornejo, Kristine M. Hutchinson, Lloyd Deng, April Tomaszewicz, Keith Welch, Matthew Lyle, Stephen Dresser, Karen Cosar, Ediz F. TI BRAF/KRAS gene sequencing of sebaceous neoplasms after mismatch repair protein analysis SO HUMAN PATHOLOGY LA English DT Article DE Muir-Torre syndrome; Lynch syndrome; Sebaceous neoplasms; Mismatch repair genes; KRAS; BRAF; Microsatellite instability ID MUIR-TORRE-SYNDROME; NONPOLYPOSIS COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; LYNCH-SYNDROME; ENDOMETRIAL CANCER; KRAS MUTATIONS; BRAF MUTATION; GLAND TUMORS; CARCINOMAS; IMMUNOHISTOCHEMISTRY AB Sebaceous neoplasms are cutaneous markers for the autosomal-dominant Muir-Tone syndrome (MTS). This phenotypic variant of Lynch syndrome (LS) is caused by germline mutations in DNA mismatch repair (MMR) genes. Microsatellite instability or loss of protein expression suggests a mutation or promoter hypermethylation in 1 of the MMR. genes. BRAF gene sequencing may help to distinguish between patients with sporadic and LS-associated colorectal carcinomas with loss of MLH1 expression. LS-associated carcinomas are virtually negative for BRAF mutations, but a subset harbors KRAS mutations. The aim of our study was to test sebaceous neoplasms for V600E BRAF or KRAS mutations to determine if these mutations are associated with somatic or germline MMR defects, analogous to colorectal carcinomas. Over a 4-year period, 32 cases comprising 21 sebaceous adenomas, 3 sebaceomas, and 8 sebaceous carcinomas with sufficient material for testing were collected. MMR immunohistochemistry showed that 7 neoplasms had combined loss of MLH1-PMS2, 16 neoplasms had combined loss of MSH2-MSH6, 2 neoplasms had solitary loss of MSH6, and 7 sebaceous neoplasms had intact protein expression. BRAF/KRAS testing revealed all sebaceous neoplasms contained a wild-type BRAF gene. Two (15%) of 13 patients with MTS were found to harbor a KRAS mutation and loss of MLH1 expression. We conclude that a V600E BRAF mutation may not be helpful in distinguishing sporadic from MTS-associated sebaceous neoplasms. Further studies are needed to determine if KRAS mutations are restricted to patients with MTS or are also present in sporadic sebaceous neoplasms. (C) 2014 Elsevier Inc. All rights reserved. C1 [Cornejo, Kristine M.; Hutchinson, Lloyd; Deng, April; Tomaszewicz, Keith; Welch, Matthew; Lyle, Stephen; Dresser, Karen; Cosar, Ediz F.] Univ Massachusetts, Sch Med, UMass Mem Med Ctr, Dept Pathol, Worcester, MA 01605 USA. RP Cornejo, KM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren Bldg 225,55 Fruit St, Boston, MA 02114 USA. EM kcornejo@partners.org NR 33 TC 6 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD JUN PY 2014 VL 45 IS 6 BP 1213 EP 1220 DI 10.1016/j.humpath.2014.02.001 PG 8 WC Pathology SC Pathology GA AI1UG UT WOS:000336640000013 PM 24767862 ER PT J AU Kubiak, DW Gilmore, ET Buckley, MW Lynch, R Marty, FM Koo, S AF Kubiak, David W. Gilmore, Erin T. Buckley, Mary W. Lynch, Robert Marty, Francisco M. Koo, Sophia TI Adjunctive management of central line-associated bloodstream infections with 70% ethanol-lock therapy SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE catheter-related infections; biofilms; salvage therapy ID IN-VITRO EFFICACIES; INTRAVASCULAR DEVICES; CANDIDA-ALBICANS; CATHETER; BIOFILMS; METAANALYSIS AB Ethanol is bactericidal against most pathogens implicated in central line-associated bloodstream infections (CLABSIs) and biofilms. Current Infectious Diseases Society of America guidelines cite insufficient evidence to support adjunctive ethanol-lock therapy (ELT) for central venous catheter (CVC) salvage in patients with CLABSI in combination with systemic antimicrobial treatment. We evaluated the safety and potential efficacy of 70% ELT for CLABSI at our institution after implementation of a hospital ELT protocol. We collected data on all patients treated with adjunctive 70% ELT for catheter salvage from September 2009 to September 2011 and assessed clinical outcomes and adverse events associated with ELT. Sixty-eight hospitalized patients received 70% ELT for CVC salvage: 45 (66%) met the criteria for CLABSI. Five (11%) had persistent or recurrent bacteraemia triggering CVC removal; 28 (62%) preserved their CVC long term. There were no documented adverse events associated with ELT. Adjunctive 70% ELT is an inexpensive, well-tolerated option for CVC salvage in patients with CLABSI and warrants further investigation. C1 [Kubiak, David W.; Gilmore, Erin T.; Buckley, Mary W.; Lynch, Robert; Marty, Francisco M.; Koo, Sophia] Brigham & Womens Hosp, Boston, MA 02115 USA. [Marty, Francisco M.; Koo, Sophia] Dana Farber Canc Inst, Boston, MA 02215 USA. [Marty, Francisco M.; Koo, Sophia] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kubiak, DW (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM dwkubiak@partners.org OI Koo, Sophia/0000-0002-4973-7439 FU National Institutes of Health [AI097225] FX The work was carried out in part with support from the National Institutes of Health (AI097225 to S. K.). NR 17 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2014 VL 69 IS 6 BP 1665 EP 1668 DI 10.1093/jac/dku017 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA AH9ZU UT WOS:000336506300035 PM 24526514 ER PT J AU Hwang, TJ Hooper, DC AF Hwang, Thomas J. Hooper, David C. TI Association between fluoroquinolone resistance and resistance to other antimicrobial agents among Escherichia coli urinary isolates in the outpatient setting: a national cross-sectional study SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Letter DE urinary tract infections; ambulatory care; antimicrobial resistance; E. coli; evidence-based prescribing; public health; surveillance ID QUINOLONE RESISTANCE; SURVEILLANCE; PLASMID; WOMEN C1 [Hwang, Thomas J.] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA. [Hwang, Thomas J.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Program Regulat Therapeut & Law, Boston, MA 02115 USA. [Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Hooper, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Hwang, TJ (reprint author), Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA. EM tjhwang@fas.harvard.edu NR 10 TC 5 Z9 5 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 EI 1460-2091 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUN PY 2014 VL 69 IS 6 BP 1720 EP 1722 DI 10.1093/jac/dku029 PG 3 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA AH9ZU UT WOS:000336506300048 PM 24521853 ER PT J AU Grannan, BL Yanamadala, V Walcott, BP Stapleton, CJ Ogilvy, CS AF Grannan, Benjamin L. Yanamadala, Vijay Walcott, Brian P. Stapleton, Christopher J. Ogilvy, Christopher S. TI Repeated neurovascular imaging in subarachnoid hemorrhage when initial studies are negative SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Angiography; Cerebral angiography; Intracranial aneurysm; Subarachnoid hemorrhage ID CATHETER ANGIOGRAPHY; CEREBRAL ANEURYSMS; CLINICAL-COURSE; CT AB Approximately 15% of patients with non-traumatic subarachnoid hemorrhage have no causative lesion identified on their initial angiogram. We present two patients with non-traumatic subarachnoid hemorrhage with negative initial angiograms who were subsequently found to have small basilar perforator aneurysms on delayed neurovascular imaging. We discuss the possible mechanisms for false negative diagnostic cerebral angiograms. These patients support the current standard of care with repeat angiography in cases of subarachnoid hemorrhage when no causative lesion can be identified on initial neurovascular imaging. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St,White Bldg Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU Brain Aneurysm Foundation FX Grant support for this work was provided to B.P.W. by the Brain Aneurysm Foundation. The funders had no role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. NR 14 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JUN PY 2014 VL 21 IS 6 BP 993 EP 996 DI 10.1016/j.jocn.2013.11.002 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AI2QT UT WOS:000336703800019 PM 24398343 ER PT J AU Simon, MV Sheth, SA Eckhardt, CA Kilbride, RD Braver, D Williams, Z Curry, W Cahill, D Eskandar, EN AF Simon, Mirela V. Sheth, Sameer A. Eckhardt, Christine A. Kilbride, Ronan D. Braver, Diana Williams, Ziv Curry, William Cahill, Dan Eskandar, Emad N. TI Phase reversal technique decreases cortical stimulation time during motor mapping SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Cortical stimulation; Motor mapping; Phase reversal technique ID BRAIN-TUMORS; EPILEPSY SURGERY; INTRAOPERATIVE STIMULATION; STIMULUS THRESHOLDS; SENSORIMOTOR CORTEX; SURGICAL RESECTION; PROGNOSTIC-FACTORS; EVOKED-POTENTIALS; CENTRAL REGION; LOW-GRADE AB Neurophysiologic mapping of the primary motor cortex (PMC) is commonly used in supratentorial surgery. Electrical cortical stimulation is guided by anatomic landmarks towards the precentral gyms, with recording of the triggered primary motor responses (TPMR) in the contralateral hemibody. Thus, factors such as distortion of the pericentral anatomy, small surgical fields, brain shifts and miscalibrated neuro-navigational systems may lengthen the process and result in unnecessary stimulations, increasing the probability of triggering seizures. We hypothesized that central sulcus localization via the median somatosensory evoked potentials phase reversal technique (MSSEP PRT) accurately guides the surgeon, resulting in prompt identification of the PMC with minimal electrical stimulation. Multivariate Cox regression was used to study the impact of MSSEP PRT on time spent performing electrical cortical stimulation to TPMR. The analysis was adjusted for presence of increased cortical excitability, high motor thresholds, lesions close to PMC and fMRI data, in 100 consecutive standardized motor mapping procedures for brain tumor resection and epilepsy surgery. Phase reversal and change morphology of the recorded somatosensory evoked potentials quadrupled (hazard ratio [HR] 4.13, p < 0.0001) and doubled (HR 2.14, p = 0.02) the rate of obtaining TPMR, respectively. A 1 mA increase in motor threshold decreased the rate by 9% (HR 0.91, p = 0.0002). Afterdischarges triggered before TPMR and lesions in close proximity to PMC decreased the rate of TPMR by 76% (HR 0.23, p <0.0001) and 48% (HR 0.52, p = 0.04), respectively. Informative PRT decreases stimulation time. Afterdischarges triggered before TPMR, high motor thresholds and lesions close to the PMC increase it. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Simon, Mirela V.; Kilbride, Ronan D.; Braver, Diana] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Simon, Mirela V.; Sheth, Sameer A.; Eckhardt, Christine A.; Kilbride, Ronan D.; Braver, Diana; Williams, Ziv; Curry, William; Cahill, Dan; Eskandar, Emad N.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Sheth, Sameer A.; Eckhardt, Christine A.; Williams, Ziv; Curry, William; Cahill, Dan; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Sheth, Sameer A.] Columbia Univ, Dept Neurol Surg, New York, NY USA. [Kilbride, Ronan D.] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. RP Simon, MV (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM MVSIMON@mgh.harvard.edu NR 39 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JUN PY 2014 VL 21 IS 6 BP 1011 EP 1017 DI 10.1016/j.jocn.2013.12.015 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AI2QT UT WOS:000336703800023 PM 24679940 ER PT J AU Mizutani, K Park, K Mima, A Katagiri, S King, GL AF Mizutani, K. Park, K. Mima, A. Katagiri, S. King, G. L. TI Obesity-associated Gingival Vascular Inflammation and Insulin Resistance SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE periodontitis; protein kinase C; oxidative stress; endothelial nitric oxide synthase; periodontal bone loss; NF-kappa B ID PROTEIN-KINASE-C; PERIODONTAL-DISEASE; NITRIC-OXIDE; RATS; MECHANISMS; ACTIVATION; BONE; PHOSPHORYLATION; DYSFUNCTION; EXPRESSION AB Obesity is a risk factor for periodontitis, but the pathogenic mechanism involved is unclear. We studied the effects of insulin in periodontal tissues during the state of obesity-induced insulin resistance. Gingival samples were collected from fatty (ZF) and lean (ZL, control) Zucker rats. Endothelial nitric oxide synthase (eNOS) expression was decreased, and activities of protein kinase C (PKC) alpha, beta 2, delta, and epsilon isoforms were significantly increased in the gingiva from ZF rats compared with those from ZL rats. Expression of oxidative stress markers (mRNA) and the p65 subunit of NF-kappa B was significantly increased in ZF rats. Immunohistochemistry revealed that NF-kappa B activation was also increased in the gingival endothelial cells from transgenic mice overexpressing NF-kappa B-dependent enhanced green fluorescent protein (GFP) and on a high-fat vs. normal chow diet. Analysis of the gingiva showed that insulin-induced phosphorylation of IRS-1, Akt, and eNOS was significantly decreased in ZF rats, but Erk1/2 activation was not affected. General PKC inhibitor and an anti-oxidant normalized the action of insulin on Akt and eNOS activation in the gingiva from ZF rats. This provided the first documentation of obesity-induced insulin resistance in the gingiva. Analysis of our data suggested that PKC activation and oxidative stress may selectively inhibit insulin-induced Akt and eNOS activation, causing endothelial dysfunction and inflammation. C1 [Mizutani, K.; Park, K.; Mima, A.; Katagiri, S.; King, G. L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02163 USA. [Mizutani, K.] Tokyo Med & Dent Univ, Dept Periodontol, Grad Sch Med & Dent Sci, Tokyo, Japan. [Mima, A.] Kinki Univ, Nara Hosp, Fac Med, Dept Nephrol & Hematol, Osaka, Japan. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02163 USA. EM George.King@joslin.harvard.edu FU National Institutes of Health/NIDDK [RO1 DK053105-13, 5P30 DK 36836]; Hiroo Kaneda Scholarship, Sunstar Foundation, Japan; Japan Society for the Promotion of Science [25862043, 24890148]; Takeda Science Foundation FX This work was supported by a National Institutes of Health/NIDDK RO1 DK053105-13 grant to G. L. K. K. M. is the recipient of a Research Fellowship (Hiroo Kaneda Scholarship, Sunstar Foundation, Japan) and a Grant-in-Aid for Young Scientists(B) 25862043 from the Japan Society for the Promotion of Science. A. M. is the recipient of a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (24890148) and the Takeda Science Foundation. This project was also supported by a National Institutes of Health/NIDDK 5P30 DK 36836 grant to the Specialized Assay Core of the Joslin Diabetes Center. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 25 TC 4 Z9 4 U1 0 U2 3 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 JUN PY 2014 VL 93 IS 6 BP 596 EP 601 DI 10.1177/0022034514532102 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AH9WP UT WOS:000336496100011 PM 24744283 ER PT J AU Joseph, J AF Joseph, Jacob TI Needling the heart to rejuvenate: The promise of intramyocardial injection of bone marrow stem cells SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Editorial Material ID DISEASE; METALLOPROTEINASES; INHIBITORS; LEUKEMIA C1 [Joseph, Jacob] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Boston, MA 02115 USA. [Joseph, Jacob] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Joseph, J (reprint author), Harvard Univ, VA Boston Healthcare Syst, Sch Med, Boston, MA 02115 USA. NR 7 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 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JUN PY 2014 VL 33 IS 6 BP 565 EP 566 DI 10.1016/j.healun.2014.02.029 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA AI1TG UT WOS:000336637100002 PM 24726425 ER PT J AU Schwabl, P Payer, BA Grahovac, J Klein, S Horvatits, T Mitterhauser, M Stift, J Boucher, Y Trebicka, J Trauner, M Angermayr, B Fuhrmann, V Reiberger, T Peck-Radosavljevic, M AF Schwabl, Philipp Payer, Berit A. Grahovac, Jelena Klein, Sabine Horvatits, Thomas Mitterhauser, Markus Stift, Judith Boucher, Yves Trebicka, Jonel Trauner, Michael Angermayr, Bernhard Fuhrmann, Valentin Reiberger, Thomas Peck-Radosavljevic, Markus TI Pioglitazone decreases portosystemic shunting by modulating inflammation and angiogenesis in cirrhotic and non-cirrhotic portal hypertensive rats SO JOURNAL OF HEPATOLOGY LA English DT Article DE Angiogenesis; Inflammation; Portal hypertension; BDL; PPVL; Pioglitazone; Portosystemic shunting; PPAR gamma ID ACTIVATED RECEPTOR-GAMMA; HYPERDYNAMIC SPLANCHNIC CIRCULATION; NITRIC-OXIDE SYNTHASE; NONALCOHOLIC STEATOHEPATITIS; GROWTH-FACTOR; PRESSURE; ROSIGLITAZONE; INHIBITION; PLACEBO; KINASE AB Background & Aims: Development of the portal-hypertensive syndrome is mediated by splanchnic inflammation and neoangiogenesis. Since peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists like pioglitazone (PIO) regulate inflammatory response and inhibit angiogenesis in endothelial cells, we evaluated PIO as treatment for experimental portal hypertension. Methods: PIO (10 mg/kg) or vehicle (VEH) was administered from day 21-28 after bile duct ligation (BDL), from day 0-7 after partial portal vein ligation (PPVL) or sham-operation (SO), respectively. After treatment, systemic hemodynamics, splanchnic blood flow (SMABF), portal pressure (PP), and portosystemic shunting (PSS) were assessed. Splanchnic and hepatic tissues were analyzed for angiogenic and inflammatory markers. Results: BDL and PPVL showed significantly increased PP, SMABF, and PSS compared to SO-VEH rats. While PIO treatment did not decrease PP or SMABF, PSS was significantly reduced both in cirrhotic (BDL-VEH: 71% to BDL-PIO: 41%; p < 0.001) and non-cirrhotic (PPVL-VEH: 62% to PPVL-PIO: 40%; p = 0.041) rats. PIO (10 mu M, in vitro) inhibited endothelial cell migration and significantly increased PPAR gamma activity in vivo. In BDL rats, PIO decreased hepatic mRNA levels of PPAR gamma (p = 0.01) and PlGF (p = 0.071), and splanchnic mRNA expression of PPAR gamma (p = 0.017), PDGF beta (p = 0.053) and TNF alpha (p = 0.075). Accordingly, splanchnic protein expression of PPAR gamma (p = 0.032), VEGFR2 (p = 0.035), CD31 (p = 0.060) and PDGF beta (p = 0.066) were lower in BDL-PIO vs. BDL-VEH animals. In PPVL rats, PIO treatment decreased splanchnic gene expression of Ang2 (-12.4 fold), eNOS (-9.3 fold), PDGF (-7.0 fold), PlGF (-11.9 fold), TGFb (-8.3 fold), VEGF-A (-11.3 fold), VEGFR1 (-5.9 fold), IL1b (-14.4 fold), and IL6 (-9.6 fold). Conclusions: Pioglitazone treatment decreases portosystemic shunting via modulation of splanchnic inflammation and neoangiogenesis. Pioglitazone should be assessed for potential beneficial effects in patients with portosystemic collaterals due to portal hypertension. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved. C1 [Schwabl, Philipp; Payer, Berit A.; Horvatits, Thomas; Trauner, Michael; Angermayr, Bernhard; Fuhrmann, Valentin; Reiberger, Thomas; Peck-Radosavljevic, Markus] Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, A-1090 Vienna, Austria. [Schwabl, Philipp; Payer, Berit A.; Angermayr, Bernhard; Reiberger, Thomas; Peck-Radosavljevic, Markus] Vienna Hepat Hemodynam Lab, Vienna, Austria. [Grahovac, Jelena; Boucher, Yves; Reiberger, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Grahovac, Jelena; Boucher, Yves; Reiberger, Thomas] Harvard Univ, Sch Med, Boston, MA USA. [Klein, Sabine; Trebicka, Jonel] Univ Bonn, Dept Internal Med 1, Div Gastroenterol & Hepatol, Bonn, Germany. [Mitterhauser, Markus] Med Univ Vienna, Dept Nucl Med, A-1090 Vienna, Austria. [Stift, Judith] Med Univ Vienna, Dept Pathol, A-1090 Vienna, Austria. RP Peck-Radosavljevic, M (reprint author), Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM markus.peck@meduniwien.ac.at OI Grahovac, Jelena/0000-0003-1430-8682; Trebicka, Jonel/0000-0002-7028-3881 FU Joseph-Skoda-Forschungsforderungspreis of the Austrian Society of Internal Medicine (OEGIM); Max-Kade Fellowship; Deutsche Forschungsgemeinschaft [SFB TRR57 P18]; HW & J Hector Stiftung FX This study and the work of PS were supported by Joseph-Skoda-Forschungsforderungspreis of the Austrian Society of Internal Medicine (OEGIM) to VF and TR. The work of TR was partly funded by a Max-Kade Fellowship. This is study was partly supported by grants from Deutsche Forschungsgemeinschaft (SFB TRR57 P18 to JT.) and by grants of the HW & J Hector Stiftung (to JT). NR 39 TC 7 Z9 8 U1 0 U2 3 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 JUN PY 2014 VL 60 IS 6 BP 1135 EP 1142 DI 10.1016/j.jhep.2014.01.025 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH9BO UT WOS:000336434300007 PM 24530596 ER PT J AU Op den Dries, S Westerkamp, AC Karimian, N Gouw, ASH Bruinsma, BG Markmann, JF Lisman, T Yeh, H Uygun, K Martins, PN Porte, RJ AF Op den Dries, Sanna Westerkamp, Andrie C. Karimian, Negin Gouw, Annette S. H. Bruinsma, Bote G. Markmann, James F. Lisman, Ton Yeh, Heidi Uygun, Korkut Martins, Paulo N. Porte, Robert J. TI Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures SO JOURNAL OF HEPATOLOGY LA English DT Article DE Bile duct injury; Donation after cardiac death; Non-anastomotic biliary strictures; Biliary complications; Ischemic cholangiopathy; Regeneration; Ischemic type biliary injury; Liver transplantation ID BILE-DUCTS; MACHINE PERFUSION; CARDIAC DEATH; COLD-STORAGE; DONOR LIVERS; CELLS; COMPLICATIONS; CONSEQUENCES; REGENERATION; ISCHEMIA AB Background & Aims: The peribiliary glands of large bile ducts have been identified as a niche of progenitor cells that contribute to regeneration of biliary epithelium after injury. We aimed to determine whether injury to the peribiliary glands of donor livers is a risk factor for development of non-anastomotic biliary strictures (NAS) after liver transplantation. Methods: In 128 liver transplant procedures, biopsies were taken from the donor bile duct and injury was assessed using an established histological grading system. Histological severity of injury was subsequently compared in liver grafts that later developed biliary structures vs. uncomplicated liver grafts. Results: Luminal biliary epithelial loss >50% was observed in 91.8% of the grafts before transplantation, yet NAS occurred in only 16.4%. Periluminal peribiliary glands were more severely injured than deep peribiliary glands located near the fibromuscular layer (>50% loss in 56.9% vs. 17.5%, respectively; p <0.001). Injury of deep peribiliary glands was more prevalent and more severe in livers that later developed NAS, compared to grafts without NAS (>50% loss in 50.0% vs. 9.8%, respectively; p = 0.004). In parallel, injury of the peribiliary vascular plexus was more severe in livers that developed NAS, compared to grafts without NAS (>50% vascular changes in 57.1% vs. 20.3%; p = 0.006). Conclusion: Injury of peribiliary glands and vascular plexus before transplantation is strongly associated with the occurrence of biliary strictures after transplantation. This suggests that insufficient regeneration due to loss of peribiliary glands or impaired blood supply may explain the development of biliary strictures. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved. C1 [Op den Dries, Sanna; Westerkamp, Andrie C.; Karimian, Negin; Lisman, Ton; Porte, Robert J.] Univ Groningen, Univ Med Ctr Groningen, Dept Surg, Sect Hepatobiliary Surg & Liver Transplantat, Groningen, Netherlands. [Op den Dries, Sanna; Markmann, James F.; Yeh, Heidi; Martins, Paulo N.] Harvard Univ, Sch Med, Dept Surg, Div Transplantat,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gouw, Annette S. H.] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands. [Bruinsma, Bote G.; Uygun, Korkut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA USA. [Bruinsma, Bote G.; Uygun, Korkut] Shriners Burns Hosp, Boston, MA USA. RP Porte, RJ (reprint author), Univ Med Ctr Groningen, Dept Surg, Sect Hepatobiliary Surg & Liver Transplantat, POB 30-001, NL-9700 RB Groningen, Netherlands. EM r.j.porte@umcg.nl OI Lisman, Ton/0000-0002-3503-7140 FU Netherlands Digestive Diseases Foundation (Maag Lever Darm Stichting); European Society for Organ Transplantation; Ubbo Emmius Foundation in Groningen; National Institutes of Health [R01DK096075, R01EB008678]; Shriners Hospitals for Children FX This research work was financially supported by grants provided by The Netherlands Digestive Diseases Foundation (Maag Lever Darm Stichting), the European Society for Organ Transplantation and the Ubbo Emmius Foundation in Groningen (all to SODD). For US studies, funding from the National Institutes of Health (R01DK096075, R01EB008678), and the Shriners Hospitals for Children are gratefully acknowledged. NR 30 TC 32 Z9 32 U1 0 U2 1 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 JUN PY 2014 VL 60 IS 6 BP 1172 EP 1179 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AH9BO UT WOS:000336434300012 PM 24560661 ER PT J AU Markowitz, JT Volkening, LK Laffel, LMB AF Markowitz, Jessica T. Volkening, Lisa K. Laffel, Lori M. B. TI Care Utilization in a Pediatric Diabetes Clinic: Cancellations, Parental Attendance, and Mental Health Appointments SO JOURNAL OF PEDIATRICS LA English DT Article ID GLYCEMIC CONTROL; METABOLIC-CONTROL; YOUNG-ADULTS; PATERNAL INVOLVEMENT; DEPRESSIVE SYMPTOMS; FAMILY CONFLICT; TYPE-1; ADOLESCENTS; YOUTH; MANAGEMENT AB Objective To examine care utilization, family attendance, and hemoglobin A1c levels in a multidisciplinary pediatric diabetes clinic. Study design This retrospective electronic record review of deidentified data included patients (99% with type 1 diabetes) with established diabetes care, aged <30 years (mean age, 15 +/- 5.2 years), and duration of diabetes >1 year (mean 8.5 +/- 5.1 years) at first visit during a 2-year period. Outcomes included care utilization, family attendance, and glycemic control, as indicated by hemoglobin A1c level. Analyses included t tests, ANOVA, chi(2) tests, ORs and 95% CIs, and multivariate analyses. Results The study cohort comprised 1771 patients, with a mean of 5.8 +/- 2.8 visits per patient. Roughly 15% of the scheduled appointments resulted in a cancellation or no-show; 61% of patients missed >= 1 visit. Patients with >= 2 missed appointments had higher A1c values and were older than those with <2 missed visits. Almost one-half of visits were attended by mothers alone; fathers attended 22% of visits. Patients whose fathers attended >= 1 visit had lower A1c values than patients whose fathers never attended. Eighteen percent of patients had onsite mental health visits. Patients with >= 1 mental health visit had higher mean A1c values, shorter duration of diabetes, and were younger compared with those with no mental health visits. Conclusion Our observations suggest the need to encourage attendance at diabetes visits and to include fathers to improve A1c values. The high rate of missed visits, especially in patients with poor glycemic control, identifies wasted provider effort when late cancellations/no-shows result in vacant clinic time. It is important to explore reasons for missed visits and to identify approaches to maximizing attendance, such as extended evening/weekend clinic hours and virtual visits. C1 [Markowitz, Jessica T.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. RP Markowitz, JT (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM jessica.markowitz@joslin.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [K23DK092335, P30DK036836]; Eleanor Chesterman Beatson Fund; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund FX Funded by the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK092335 and P30DK036836), the Eleanor Chesterman Beatson Fund, the Katherine Adler Astrove Youth Education Fund, and the Maria Griffin Drury Pediatric Fund. The authors declare no conflicts of interest. NR 45 TC 5 Z9 5 U1 5 U2 7 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 JUN PY 2014 VL 164 IS 6 BP 1384 EP 1389 DI 10.1016/j.jpeds.2014.01.045 PG 6 WC Pediatrics SC Pediatrics GA AH9YX UT WOS:000336503200031 PM 24612905 ER PT J AU Landsman-Blumberg, PB Wei, WH Douglas, D Smith, DM Clark, S Camargo, CA AF Landsman-Blumberg, Pamela B. Wei, Wenhui Douglas, Damon Smith, David M. Clark, Sunday Camargo, Carlos A., Jr. TI Concordance with Recommended Postdischarge Care Guidelines among Children with Food-Induced Anaphylaxis SO JOURNAL OF PEDIATRICS LA English DT Article ID LONG-TERM MANAGEMENT; ALLERGY AB Objective To describe patient characteristics, concordance with recommended postdischarge care, and risk of repeat events within a cohort of children discharged from an emergency department (ED) or hospital for food-induced anaphylaxis in the US. Study design Children (aged <18 years) with an ED visit/hospitalization for food-induced anaphylaxis were identified from the 2002-2008 Truven Health MarketScan databases using an expanded International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code algorithm. The initial identified ED visit/hospitalization was the index event. Claims data for the children with continuous medical and prescription coverage for >= 1 year before and after the index event were evaluated. Analyses included the rates of 1-year postdischarge epinephrine autoinjector (EAI) prescription fills, allergist/immunologist visits, and repeat events. Results The study cohort comprised 1009 patients with an average age of 7 years, including 58% males, 27% with a history of asthma, and 90% discharged from an ED. Within 1 year postdischarge, 83% had an EAI prescription fill (69% within 1 week postdischarge), 43% had a specialist visit (51% within 4 weeks postdischarge), and 6.4% had evidence of another anaphylaxis-related ED visit/hospitalization. Conclusion Among children with food-induced anaphylaxis, within 1 year postdischarge from the ED or hospital, concordance was higher for EAI prescription fills than for allergist/immunologist visits. Subsequent ED visits/hospital stays for anaphylactic events were low. More research is needed to identify barriers between recommendations and physician/patient behaviors, as well as the impact of not following the recommendations on patient outcomes and healthcare costs. C1 [Landsman-Blumberg, Pamela B.; Smith, David M.] Truven Hlth Analyt, Bethesda, MD USA. [Wei, Wenhui] Sanofi US, Bridgewater, NJ USA. [Douglas, Damon] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org FU Sanofi US FX Funded by Sanofi US. P.L.-B. and D. S. are employees of Truven Health Analytics (formerly the Healthcare Division of Thomson Reuters). W. W. is an employee of Sanofi US. D. D. was a Rutgers Fellow on assignment at Sanofi US until 2011. C. C. is a consultant for Sanofi US and Dey Pharma. NR 20 TC 1 Z9 1 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2014 VL 164 IS 6 BP 1444 EP + DI 10.1016/j.jpeds.2014.02.022 PG 6 WC Pediatrics SC Pediatrics GA AH9YX UT WOS:000336503200041 PM 24661339 ER PT J AU Vergamini, LB Frazier, AL Abrantes, FL Ribeiro, KB Rodriguez-Galindo, C AF Vergamini, Lucas Bonachi Frazier, A. Lindsay Abrantes, Fernanda Laurinavicius Ribeiro, Karina Braga Rodriguez-Galindo, Carlos TI Increase in the Incidence of Differentiated Thyroid Carcinoma in Children, Adolescents, and Young Adults: A Population-Based Study SO JOURNAL OF PEDIATRICS LA English DT Article ID HIGH-INCIDENCE AREA; UNITED-STATES; CANCER INCIDENCE; NEW-CALEDONIA; TRENDS; RISK; SMOKING; ENGLAND; PEOPLE; IODINE AB Objective To investigate trends in incidence of differentiated thyroid carcinomas among children and adolescents and young adults. Study design In this ecological time-trends study, we selected cases of differentiated thyroid carcinomas (19842010) in patients <30 years from Surveillance, Epidemiology, and End Results 9 cancer registries by using International Classification of Diseases for Oncology, 3rd edition, codes for papillary and follicular cancers. Patients with multiple other primary diseases before differentiated thyroid carcinomas were excluded. SEER*Stat software, version 8.0.4 (National Cancer Institute, Bethesda, Maryland) was used to calculate age-standardized rates (estimated per 1 000 000/persons) and annual percentage changes (APCs) were calculated by the Joinpoint model (Joinpoint software, version 4.0.4; National Cancer Institute). Results Rates ranged from 2.77 (1990) to 9.63 (2009) and from 18.35 (1987) to 50.99 (2009), for male and female subjects, respectively. A significant increasing trend in incidence was observed for both male (APC 3.44; 95% CI 2.60-4.28) and female (APC 3.81; 95% CI 3.38-4.24) patients. When a stratified analysis on the basis of tumor size was performed, significant increasing trends were noted for the following categories: <0.5 cm (females: APC 5.09, 95% CI 3.54-6.65), 0.5-0.9 cm (females: APC 8.45, 95% CI 7.09-9.82), 1.0-1.9 cm (males: APC 5.09, 95% CI 3.20-7.01; females: APC 3.42, 95% CI 2.78-4.07), and >= 2 cm(males: APC 2.62, 95% CI 1.64-3.60; females: APC 2.96, 95% CI 2.34-3.59). Conclusions Incidence rates for differentiated thyroid carcinomas are increasing among children and adolescents and young adults in the US. The increasing trends for larger tumors rules out diagnostic scrutiny as the only explanation for the observed results. Environmental, dietary, and genetic influences should be investigated. C1 [Vergamini, Lucas Bonachi; Abrantes, Fernanda Laurinavicius; Ribeiro, Karina Braga] Santa Casa Sao Paulo, Fac Med Sci, Sao Paulo, Brazil. [Frazier, A. Lindsay; Rodriguez-Galindo, Carlos] Dana Farber Boston Childrens Ctr Canc & Blood Dis, Boston, MA USA. [Frazier, A. Lindsay; Rodriguez-Galindo, Carlos] Harvard Univ, Sch Med, Boston, MA USA. RP Rodriguez-Galindo, C (reprint author), Dana Farber Canc Inst, 450 Brookline Ave D3-313, Boston, MA 02215 USA. EM carlos_rodriguez-galindo@dfci.harvard.edu FU program "Pesquisadores do Futuro"- Faculty of Medicine Sciences of Santa Casa of Sao Paulo, Brazil FX L.V. was recipient of a scholarship from the program "Pesquisadores do Futuro"- Faculty of Medicine Sciences of Santa Casa of Sao Paulo, Brazil. The authors declare no conflicts of interest. NR 34 TC 31 Z9 38 U1 0 U2 4 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 JUN PY 2014 VL 164 IS 6 BP 1481 EP 1485 DI 10.1016/j.jpeds.2014.01.059 PG 5 WC Pediatrics SC Pediatrics GA AH9YX UT WOS:000336503200047 PM 24630354 ER PT J AU Lin, F Roiland, R Heffner, K Johnson, M Chen, DG Mapstone, M AF Lin, Feng Roiland, Rachel Heffner, Kathi Johnson, Melissa Chen, Ding-Geng (Din) Mapstone, Mark TI Evaluation of objective and perceived mental fatigability in older adults with vascular risk SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Mental fatigability; Executive control; History of mental activities; Reaction time ID COGNITIVE FATIGUE; SUBSEQUENT SYMPTOMS; MULTIPLE-SCLEROSIS; SUBJECTIVE FATIGUE; NORMATIVE DATA; HEART-FAILURE; AGE; EDUCATION; SAMPLE; MEMORY AB Objectives: Mental fatigability refers to the failure to sustain participation in tasks requiring mental effort Older adults with vascular risk are at particular risk for experiencing mental fatigability. The present study (1) tested a new way of measuring objective mental fatigability by examining its association with perceived mental fatigability; and (2) identified associated psychological, physiological, and situational predictors. Methods: A cross-sectional study was conducted with 49 community-dwelling participants aged 75 + years with vascular risk. A 20-minute fatigability-manipulation task was used to induce mental fatigability and develop objective and perceived mental fatigability measures. Objective fatigability was calculated by the change of reaction time over the course of the task. Perceived fatigability was calculated by the change of fatigue self-reported before and after the task. A set of potential psychological, physiological, and situational predictors were measured. Results: There was a significant increase in reaction time and self-reported fatigue to the fatigability manipulation task, indicating occurrence of objective and perceived mental fatigability. Reaction time and self-reported fatigue were moderately, but significantly correlated. Higher levels of executive control and having a history of more frequently engaging in mental activities were associated with lower objective mental fatigability. None of the examined factors were associated with perceived mental fatigability. Conclusion: Objective and perceived mental fatigability were sensitive to our fatigability-manipulation task. While these two measures were correlated, they were not associated with the same factors. These findings need to be validated in studies with a more heterogeneous sample and a greater variety of fatigability-manipulation tasks. (C) 2014 Elsevier Inc. All rights reserved. C1 [Lin, Feng; Johnson, Melissa; Chen, Ding-Geng (Din)] Univ Rochester, Sch Nursing, Rochester, NY 14642 USA. [Lin, Feng; Heffner, Kathi] Univ Rochester, Dept Psychiat, Sch Med & Dent, 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 Biol, Rochester, NY 14642 USA. [Mapstone, Mark] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. RP Lin, F (reprint author), Univ Rochester, Med Ctr, HWH 2w128,601 Elmwood Ave, Rochester, NY 14642 USA. EM vankee_lin@urmc.rochester.edu OI Heffner, Kathi/0000-0003-1095-1873 FU University of Rochester CTSA from the National Center for Advancing Translational Sciences of the National Institutes of Health [KL2 TR000095]; Sigma Theta Tau International Small Grants FX Data collection of the present project was supported by Sigma Theta Tau International Small Grants to F. Lin. The manuscript preparation 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 52 TC 0 Z9 0 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUN PY 2014 VL 76 IS 6 BP 458 EP 464 DI 10.1016/j.jpsychores.2014.04.001 PG 7 WC Psychiatry SC Psychiatry GA AI1UA UT WOS:000336639300004 PM 24840140 ER PT J AU Cox, K McAdams, DP AF Cox, Keith McAdams, Dan P. TI Meaning making during high and low point life story episodes predicts emotion regulation two years later: How the past informs the future SO JOURNAL OF RESEARCH IN PERSONALITY LA English DT Article DE Narrative identity; Emotion regulation; Emotional memory ID AUTOBIOGRAPHICAL MEMORIES; ADOLESCENCE AB Memory processes are commonly thought to relate to a host of personality systems. The current study specifies a particular way that memory relates to personality. Highly-valenced, identity-rich memories - high and low point episodes in the life story - were analyzed to see if aspects of these memories predicted self-reports of emotion regulation two years later. Meaning making in high and low points predicted emotion regulation. Moreover, valence mattered. Positive meaning making in high and low point stories predicted positive emotion regulation while negative meaning making in low point stories predicted negative emotion regulation. These relationships held while controlling for baseline extraversion, neuroticism, and memory word count. Limitations due to study design are discussed. Published by Elsevier Inc. C1 [Cox, Keith] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Cox, Keith] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [McAdams, Dan P.] Northwestern Univ, Dept Psychol, Evanston, IL 60208 USA. [McAdams, Dan P.] Sch Educ & Social Policy, Evanston, IL USA. RP Cox, K (reprint author), Ralph H Johnson VA Med Ctr, Charleston, SC USA. EM keith.cox@va.gov NR 14 TC 9 Z9 9 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0092-6566 EI 1095-7251 J9 J RES PERS JI J. Res. Pers. PD JUN PY 2014 VL 50 BP 66 EP 70 DI 10.1016/j.jrp.2014.03.004 PG 5 WC Psychology, Social SC Psychology GA AI2TA UT WOS:000336709800009 ER PT J AU Bent, S Hendren, RL Zandi, T Law, K Choi, JE Widjaja, F Kalb, L Nestle, J Law, P AF Bent, Stephen Hendren, Robert L. Zandi, Tara Law, Kiely Choi, Jae-Eun Widjaja, Felicia Kalb, Luther Nestle, Jay Law, Paul TI Internet-Based, Randomized, Controlled Trial of Omega-3 Fatty Acids for Hyperactivity in Autism SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE autism; nutritional supplement; alternative medicine; hyperactivity ID PERVASIVE DEVELOPMENTAL DISORDERS; PLACEBO-CONTROLLED-TRIAL; SPECTRUM DISORDERS; PARENT REPORT; CHILDREN; METHYLPHENIDATE; SUPPLEMENTATION; IRRITABILITY; ARIPIPRAZOLE; RISPERIDONE AB Objective: Preliminary evidence suggests that omega-3 fatty acids may reduce hyperactivity in children with autism spectrum disorder (ASD). We sought to examine the feasibility of a novel, Internet-based clinical trial design to evaluate the efficacy of this supplement. Method: E-mail invitations were sent to parents of children aged 5 to 8 years enrolled in the Interactive Autism Network. All study procedures, including screening, informed consent, and collection of outcome measures took place over the Internet. The primary Outcome measures were parent- and teacher-rated changes in hyperactivity on the Aberrant Behavior Checklist (ABC-H). Results: During the 6-week recruitment period, 57 children from 28 states satisfied all eligibility criteria and were randomly assigned to 1.3 grams of omega-3 fatty acids or an identical placebo daily for 6 weeks. Outcome assessments were obtained from all 57 participants and 57 teachers, and the study was completed in 3 months. Children in the omega-3 fatty acid group had a greater reduction in hyperactivity (-5.3 points) compared to the placebo group (-2.6 points), but the difference was not statistically significant (1.9-point greater improvement in the omega-3 group, 95% CI = -2.2 to 5.2). Adverse events were rare and not associated with omega-3 fatty acids. Participant feedback was positive. Conclusion: Internet-based, randomized controlled trials of therapies in children with ASD are feasible and may lead to marked reductions in the time and cost of completing trials. A larger sample size is required to definitively determine the efficacy of omega-3 fatty acids. Clinical trial registration information-Omega-3 Fatty Acids for Hyperactivity Treatment in Autism Spectrum Disorder; http://clinicaltrials.gov; NCT 01694667. C1 [Bent, Stephen; Hendren, Robert L.; Choi, Jae-Eun; Widjaja, Felicia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Zandi, Tara; Law, Kiely; Kalb, Luther; Nestle, Jay; Law, Paul] Kennedy Krieger Inst, Baltimore, MD USA. RP Bent, S (reprint author), San Francisco VA Med Ctr, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. EM Stephen.Bent@ucsf.edu FU Simons Foundation [SFARI 206484]; National Center for Research Resources; National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 RR024131] FX This work was supported by a grant from the Simons Foundation (SFARI 206484, S.B.) and 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. NR 25 TC 9 Z9 10 U1 2 U2 25 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 JUN PY 2014 VL 53 IS 6 BP 658 EP 666 DI 10.1016/j.jaac.2014.01.018 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA AI0SO UT WOS:000336560400009 PM 24839884 ER PT J AU Kohn, R Kratz, JR Markmann, JF Vagefi, PA AF Kohn, Rachel Kratz, Johannes R. Markmann, James F. Vagefi, Parsia A. TI The Migrated Liver Transplantation Candidate: Insight into Geographic Disparities in Liver Distribution SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the New-England-Surgical-Society CY SEP, 2013 CL Hartford, CT SP New England Surg Soc ID KIDNEY AB BACKGROUND: A minority of liver transplantation (LT) candidates pursue listing at multiple centers to achieve transplantation. The purpose of this study was to assess the characteristics and outcomes of the migrated LT candidates, that is, those who travel to secondary centers seeking LT. STUDY DESIGN: Single-center retrospective study from January 1, 2005 to January 1, 2013 at a tertiary care center within United Network for Organ Sharing Region 1. Adult recipients who were listed at the primary center of interest, but subsequently achieved transplantation at a secondary center (Massachusetts General Hospital [MGH]-migrated; n = 44) were compared with recipients who achieved LT at the primary center (MGH-transplanted; n = 279). RESULTS: The MGH-migrated recipients most frequently traveled to United Network for Organ Sharing Region 3 (70.5%), with a mean (+/- SD) distance traveled of 1,134 (+/- 392) miles. The MGH-migrated patients, when compared with MGH-transplanted recipients, spent more time on the waitlist (907.6 +/- 930.1 days vs 354.9 +/- 533.2 days; p < 0.00001), were more likely to have cholestatic liver disease (22.7% vs 6.8%; p = 0.0006) and private insurance (80.0% vs 51.6%; p = 0.0005), but were less likely to have alcoholic liver disease (2.3% vs 18.6%; p = 0.006) and Model for End-Stage Liver Disease exception points (6.8% vs 50.9%; p < 0.00001). On multivariable analysis, candidates with private insurance who lacked both alcoholic liver disease and Model for End-Stage Liver Disease exception point listing were significantly associated with the odds of pursuing migration. Despite achieving LT, MGH-migrated patients had inferior 5-year patient survival rates (63% vs 80%; p = 0.03). CONCLUSIONS: A small and distinctive cohort of LT recipients pursue migration to achieve transplantation. Travel patterns of migrated LT recipients appear to reflect the ongoing geographic disparities in liver distribution and underscore the need for alterations in policy to allow for equitable distribution. (C) 2014 by the American College of Surgeons C1 [Kohn, Rachel] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kratz, Johannes R.; Markmann, James F.; Vagefi, Parsia A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Kratz, Johannes R.; Markmann, James F.; Vagefi, Parsia A.] Harvard Univ, Sch Med, Boston, MA USA. RP Vagefi, PA (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, 55 Fruit St,White 544b, Boston, MA 02114 USA. EM pvagefi@partners.org NR 7 TC 7 Z9 7 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2014 VL 218 IS 6 BP 1113 EP 1118 DI 10.1016/j.jamcollsurg.2013.12.056 PG 6 WC Surgery SC Surgery GA AH9JK UT WOS:000336458000006 PM 24680570 ER PT J AU Kaafarani, HMA Mavros, MN Hwabejire, J Fagenholz, P Yeh, DD Demoya, M King, DR Alam, HB Chang, YC Hutter, M Antonelli, D Gervasini, A Velmahos, GC AF Kaafarani, Haytham M. A. Mavros, Michael N. Hwabejire, John Fagenholz, Peter Yeh, Daniel D. Demoya, Marc King, David R. Alam, Hasan B. Chang, Yuchiao Hutter, Matthew Antonelli, Donna Gervasini, Alice Velmahos, George C. TI Derivation and Validation of a Novel Severity Classification for Intraoperative Adverse Events SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the New-England-Surgical-Society CY SEP, 2013 CL Hartford, CT SP New England Surg Soc ID PATIENT SAFETY INDICATORS; CLAVIEN-DINDO CLASSIFICATION; ABDOMINAL-WALL REPAIR; SURGICAL COMPLICATIONS; POSTOPERATIVE COMPLICATIONS; GRADING SYSTEM; ENTEROTOMY; MORBIDITY; SURGERY; UTILITY AB BACKGROUND: There is currently no systematic approach to evaluating the severity of intraoperative adverse events (iAEs). STUDY DESIGN: A 3-phase project was designed to develop and validate a novel severity classification scheme for iAEs. Phase 1 created the severity classification using a modified Delphi process. Phase 2 measured the classification's internal consistency by calculating inter-rater reliability among 91 surgeons using standardized iAEs scenarios. Phase 3 measured the classification's construct validity by testing whether major iAEs (severity class >= 3) correlated with worse 30-day postoperative outcomes compared with minor iAEs (severity class <3). This was achieved by creating a matched database using American College of Surgeons NSQIP and administrative data, querying for iAEs using the Patient Safety Indicator #15 (Accidental Puncture/ Laceration), and iAE confirmation by chart review. RESULTS: Phase 1 resulted in a 6-point severity classification scheme. Phase 2 revealed an inter-rater reliability of 0.882. Of 9,292 patients, phase 3 included 181 confirmed with iAEs. All preoperative/intraoperative variables, including demographics, comorbidities, type of surgery performed, and operative length, were similar between patients with minor (n = 110) vs major iAEs (n = 71). In multivariable logistic analysis, severe iAEs correlated with higher risks of any postoperative complication (odds ratio [OR] 3.8; 95% CI, 1.9-7.4; p < 0.001), surgical site infections (OR 3.7; 95% CI, 1.7-8.2; p 0.001), systemic sepsis (OR 6.0; 95% CI, 2.1-17.2; p 0.001), failure to wean off the ventilator (OR 3.2; 95% CI, 1.2-8.9; p = 0.022), and postoperative length of stay >= 7 days (OR 3.0; 95% CI, 1.5-5.9; p = 0.002). Thirty-day mortalities were similar (4.5% vs 7.1%; p = 0.46). CONCLUSIONS: We propose a novel iAE severity classification system with high internal consistency and solid construct validity. Our classification scheme might prove essential for benchmarking quality of intraoperative care across hospitals and/or individual surgeons. (C) 2014 by the American College of Surgeons C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kaafarani, HMA (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hkaafarani@partners.org OI King, David/0000-0003-1028-1478 NR 32 TC 11 Z9 12 U1 1 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 JUN PY 2014 VL 218 IS 6 BP 1120 EP 1128 DI 10.1016/j.jamcollsurg.2013.12.060 PG 9 WC Surgery SC Surgery GA AH9JK UT WOS:000336458000008 PM 24702887 ER PT J AU Tapias, LF Morse, CR AF Tapias, Luis F. Morse, Christopher R. TI Minimally Invasive Ivor Lewis Esophagectomy: Description of a Learning Curve SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the New-England-Surgical-Society CY SEP, 2013 CL Hartford, CT SP New England Surg Soc ID CANCER; OUTCOMES; SURGERY; VOLUME; LYMPHADENECTOMY; MORTALITY AB BACKGROUND: Minimally invasive Ivor Lewis esophagectomy (MIE) is gaining popularity for the treatment of esophageal cancer. However, as it is a technically demanding operation, a learning curve should be defined to guide training and allow implementation at institutions not currently using this technique. STUDY DESIGN: Our study included a retrospective series of the first 80 consecutive patients undergoing MIE by a single surgeon with advanced training in minimally invasive esophageal surgery in independent practice at a high-volume tertiary center. Patients were stratified into 2 groups of 40 patients, with chronological order defining early and late experiences. Primary end points included conversion to open procedure, surgical time, blood loss, chest drainage duration, time to oral intake, hospital stay, postoperative morbidity, and mortality. The cumulative sum methodology was used and analyzed by visually inspecting the plots. RESULTS: Conversion to open procedure occurred in 2 (5%) patients in the early group and none in the late group (p = 0.49). Comparing early vs late experience, mean surgical time was 364 vs 316 minutes (p < 0.01), estimated blood loss was 205 vs 176 mL (p = 0.14), median hospital stay was 7 vs 6 days (p < 0.01), and morbidity was observed in 16 (40%) and 14 (35%) patients (p = 0.82), respectively. There were no anastomotic leaks or 30-day mortality. Cumulative sum plots showed decreasing surgical time after patient 54 (plateau after patient 31), decreasing chest tube duration after patients 38 and 33, sooner oral intake after patient 35, and decreased hospital stay after patient 33. CONCLUSIONS: Improved operative and perioperative parameters for MIE were observed in the last 40 patients when compared with the first 40 patients. A reasonable learning curve for MIE would require the operation and perioperative care of 35 to 40 patients. (C) 2014 by the American College of Surgeons C1 [Tapias, Luis F.; Morse, Christopher R.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Morse, CR (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM crmorse@partners.org NR 21 TC 22 Z9 23 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2014 VL 218 IS 6 BP 1130 EP 1140 DI 10.1016/j.jamcollsurg.2014.02.014 PG 11 WC Surgery SC Surgery GA AH9JK UT WOS:000336458000010 PM 24698488 ER PT J AU Ahmad, R Schmidt, BH Rattner, DW Mullen, JT AF Ahmad, Rima Schmidt, Benjamin H. Rattner, David W. Mullen, John T. TI Factors Influencing Readmission after Curative Gastrectomy for Gastric Cancer SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the New-England-Surgical-Society CY SEP, 2013 CL Hartford, CT SP New England Surg Soc ID LENGTH-OF-STAY; FEEDING JEJUNOSTOMY; PATIENT READMISSION; SURGERY; PLACEMENT; MORTALITY; RESECTION; RATES; TIME AB BACKGROUND: The incidence of, and associated risk factors for, readmission after potentially curative gastrectomy for patients with gastric cancer has not been well studied. We sought to determine the 30-day readmission rate as well as the potential risk factors for readmission at our institution in patients undergoing gastrectomy for gastric cancer with curative intent. STUDY DESIGN: We performed a retrospective analysis of all patients undergoing potentially curative gastrectomy for gastric cancer from 1995 to 2011. The 30-day hospital readmission rate was determined, and potential clinicopathologic risk factors for readmission were examined. RESULTS: Readmission to the hospital within 30 days occurred in 14.6% (61 of 418) of patients, including 6 patients who were readmitted more than once. The most common reasons for readmission included nutritional difficulties (n = 12, 20%), intra-abdominal fluid collections (n = 11, 18%), and small bowel obstruction (n = 6, 10%). Factors associated with a higher 30-day readmission rate included type of resection (total gastrectomy, 23% vs subtotal gastrectomy, 13% vs esophagogastrectomy, 9%, p = 0.016), pre-existing cardiovascular disease (17%, p = 0.05), and history of a major postoperative complication (24%, p < 0.001). Factors not associated with a higher readmission rate included advanced age, preexisting pulmonary disease, T or N stage, extent of lymph node dissection, receipt of neoadjuvant chemotherapy or radiotherapy, length of stay of the index hospitalization, and destination and level of support on discharge. CONCLUSIONS: Readmission after potentially curative gastrectomy for gastric cancer is common. Patients with pre-existing cardiovascular disease, those who suffer major postoperative complications, and those undergoing total gastric resections are at especially high risk for readmission, and strategies designed to support these high-risk patients on discharge are warranted. (C) 2014 by the American College of Surgeons C1 [Ahmad, Rima; Schmidt, Benjamin H.; Rattner, David W.; Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA. EM jmullen@partners.org NR 11 TC 9 Z9 9 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2014 VL 218 IS 6 BP 1215 EP 1222 DI 10.1016/j.jamcollsurg.2014.02.015 PG 8 WC Surgery SC Surgery GA AH9JK UT WOS:000336458000030 PM 24680567 ER PT J AU Jesinkey, SR Funk, JA Stallons, LJ Wills, LP Megyesi, JK Beeson, CC Schnellmann, RG AF Jesinkey, Sean R. Funk, Jason A. Stallons, L. Jay Wills, Lauren P. Megyesi, Judit K. Beeson, Craig C. Schnellmann, Rick G. TI Formoterol Restores Mitochondrial and Renal Function after Ischemia-Reperfusion Injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; OXIDANT INJURY; TRANSCRIPTIONAL COACTIVATOR; PROMOTES RECOVERY; PROXIMAL TUBULES; BIOGENESIS; PGC-1-ALPHA; DISEASE; EXPRESSION; REGULATOR AB Mitochondrial biogenesis may be an adaptive response necessary for meeting the increased metabolic and energy demands during organ recovery after acute injury, and renal mitochondrial dysfunction has been implicated in the pathogenesis of AKI. We proposed that stimulation of mitochondria! biogenesis 24 hours after ischemia/reperfusion (I/R)-induced AKI, when renal dysfunction is maximal, would accelerate recovery of mitochondrial and renal function in mice. We recently showed that formoterol, a potent, highly specific, and long-acting beta(2)-adrenergic agonist, induces renal mitochondrial biogenesis in naive mice. Animals were subjected to sham or I/R-induced AKI, followed by once-daily intraperitoneal injection with vehicle or formoterol beginning 24 hours after surgery and continuing through 144 hours after surgery. Treatment with formoterol restored renal function, rescued renal tubules from injury, and diminished necrosis after I/R-induced AKI. Concomitantly, formoterol stimulated mitochondrial biogenesis and restored the expression and function of mitochondrial proteins. Taken together, these results provide proof of principle that a novel drug therapy to treat AKI, and potentially other acute organ failures, works by restoring mitochondrial function and accelerating the recovery of renal function after injury has occurred. C1 [Jesinkey, Sean R.; Funk, Jason A.; Stallons, L. Jay; Wills, Lauren P.; Beeson, Craig C.; Schnellmann, Rick G.] Med Univ S Carolina, Ctr Cell Death Injury & Regenerat, Dept Drug Discovery & Biomed Sci, Charleston, SC 29425 USA. [Megyesi, Judit K.] Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA. [Schnellmann, Rick G.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), MUSC MSC 140,280 Calhoun St, Charleston, SC 29425 USA. EM schnell@musc.edu FU National Institutes of Health [R01 GM084147, T32 HL007260-35, F32DK098053, C06 RR015455, P20 GM103542-02, UL1 RR029882]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs [BX-000851]; South Carolina Clinical and Translational Research Institute FX This study was supported by the National Institutes of Health (R01 GM084147 to R.G.S., T32 HL007260-35 to S.R.J and L.J.S., F32DK098053 to L.J.S., C06 RR015455 and SC COBRE in Oxidants, Redox Balance and Stress Signaling P20 GM103542-02), and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs (BX-000851). This publication was supported, in part, by the South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina CTSA, and funded by the National Institutes of Health (UL1 RR029882). NR 30 TC 20 Z9 20 U1 0 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2014 VL 25 IS 6 BP 1157 EP 1162 DI 10.1681/ASN.2013090952 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AI0RS UT WOS:000336558100007 PM 24511124 ER PT J AU Funk, JA Janech, MG Dillon, JC Bissler, JJ Siroky, BJ Bell, PD AF Funk, Jason A. Janech, Michael G. Dillon, Joshua C. Bissler, John J. Siroky, Brian J. Bell, P. Darwin TI Characterization of Renal Toxicity in Mice Administered the Marine Biotoxin Domoic Acid SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; LIONS ZALOPHUS-CALIFORNIANUS; SEA LIONS; C-FOS; RECEPTOR ANTAGONIST; TISSUE DISTRIBUTION; SUBCLINICAL AKI; GENE-EXPRESSION; NMDA RECEPTORS; SHELLFISH AB Domoic acid (DA), an excitatory amino acid produced by diatoms belonging to the genus Pseudo-nitzschia, is a glutamate analog responsible for the neurologic condition referred to as amnesic shellfish poisoning. To date, the renal effects of DA have been underappreciated, although renal filtration is the primary route of systemic elimination and the kidney expresses ionotropic glutamate receptors. To characterize the renal effects of DA, we administered either a neurotoxic dose of DA or doses below the recognized limit of toxicity to adult Sv128/Black Swiss mice. DA preferentially accumulated in the kidney and elicited marked renal vascular and tubular damage consistent with acute tubular necrosis, apoptosis, and renal tubular cell desquamation, with toxic vacuolization and mitochondrial swelling as hallmarks of the cellular damage. Doses >= 0.1 mg/kg DA elevated the renal injury biomarkers kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, and doses >= 0.005 mg/kg induced the early response genes c-fos and junb. Coadministration of DA with the broad spectrum excitatory amino acid antagonist kynurenic acid inhibited induction of c-fos, junb, and neutrophil gelatinase-associated lipocalin. These findings suggest that the kidney may be susceptible to excitotoxic agonists, and renal effects should be considered when examining glutamate receptor activation. Additionally, these results indicate that DA is a potent nephrotoxicant, and potential renal toxicity may require consideration when determining safe levels for human exposure. C1 [Funk, Jason A.; Janech, Michael G.; Dillon, Joshua C.; Bell, P. Darwin] Med Univ S Carolina, Div Nephrol, Dept Med, Charleston, SC 29425 USA. [Bissler, John J.; Siroky, Brian J.] Cincinnati Childrens Hosp Med Ctr, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA. [Bell, P. Darwin] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Bell, PD (reprint author), Med Univ S Carolina, 70 President St,DDB 514,MSC 629, Charleston, SC 29425 USA. EM bellpd@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [T32DK007752]; Office of Naval Research [N000140810341]; Veterans Affairs Merit Grant [P30 DK074038]; Dialysis Clinic FX J.A.F. was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Training Grant T32DK007752 in Renal Function and Disease. M.G.J. was supported by Office of Naval Research Award N000140810341. This study was supported by Veterans Affairs Merit Grant P30 DK074038 and funds from Dialysis Clinic (to P.D.B.). NR 58 TC 7 Z9 7 U1 0 U2 14 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2014 VL 25 IS 6 BP 1187 EP 1197 DI 10.1681/ASN.2013080836 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA AI0RS UT WOS:000336558100010 PM 24511141 ER PT J AU Meehan, T Stecker, MS Kalva, SP Oklu, R Walker, TG Ganguli, S AF Meehan, Timothy Stecker, Michael S. Kalva, Sanjeeva P. Oklu, Rahmi Walker, T. Gregory Ganguli, Suvranu TI Outcomes of Transcatheter Arterial Embolization for Acute Hemorrhage Originating from Gastric Adenocarcinoma SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID UPPER GASTROINTESTINAL HEMORRHAGE; CANCER; MANAGEMENT; SURGERY; ENDOSCOPY; EMBOLOTHERAPY; MALIGNANCY; SURVIVAL AB Purpose: To evaluate the indications, complications, and clinical outcomes of transcatheter embolization for acute hemorrhage associated with gastric adenocarcinoma. Materials and Methods: Ten patients underwent catheter-directed arterial embolization at two institutions for acute gastrointestinal hemorrhage related to pathology-proven gastric adenocarcinoma from March 2002 to March 2012. The electronic medical record for each patient was reviewed for clinical presentation, endoscopy history, procedural complications, and long-term follow-up results. Results: Between March 2002 and March 2012, 10 patients (eight men; mean age, 61.1 y +/- 15.3) underwent transcatheter arterial embolization for gastrointestinal hemorrhage caused by gastric adenocarcinoma. Endoscopic therapy had failed in all patients before embolization. Embolization involving branches of the left gastric artery was performed in all patients. No deaths or complications related to the procedure were identified. Mean survival was 301 days, but with a wide range, from 1 day to 1,852 days and counting. Those with unresectable disease (n = 7; 70%) had a median survival time of 9 days, significantly worse (P < .01) than those with resectable disease (n = 3; 30%), who had a median survival of 792 days. Six patients, all with unresectable disease, did not live beyond 30 days. Two of the three patients with resectable disease had subsequent curative resection. conclusions: Transcatheter arterial embolization can be considered for cases of acute hemorrhagic gastric adenocarcinoma, with improved outcomes in patients with localized disease compared with nonresectable gastric adenocarcinoma. C1 [Meehan, Timothy] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Oklu, Rahmi; Walker, T. Gregory; Ganguli, Suvranu] Massachusetts Gen Hosp, Div Intervent Radiol, Boston, MA 02114 USA. [Stecker, Michael S.] Div Angiog & Intervent Radiol, Boston, MA USA. [Meehan, Timothy; Stecker, Michael S.; Oklu, Rahmi; Walker, T. Gregory; Ganguli, Suvranu] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kalva, Sanjeeva P.] Univ Texas SW Med Ctr Dallas, Dept Intervent Radiol, Dallas, TX 75390 USA. RP Ganguli, S (reprint author), Massachusetts Gen Hosp, Div Intervent Radiol, 55 Fruit St, Boston, MA 02114 USA. EM sganguli@partners.org NR 27 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUN PY 2014 VL 25 IS 6 BP 847 EP 851 DI 10.1016/j.jvir.2014.02.005 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA AI1TY UT WOS:000336639100004 PM 24657087 ER PT J AU Chao, TE Sharma, K Mandigo, M Hagander, L Resch, SC Weiser, TG Meara, JG AF Chao, Tiffany E. Sharma, Ketan Mandigo, Morgan Hagander, Lars Resch, Stephen C. Weiser, Thomas G. Meara, John G. TI Cost-effectiveness of surgery and its policy implications for global health: a systematic review and analysis SO LANCET GLOBAL HEALTH LA English DT Review ID ADJUSTED LIFE YEARS; SUB-SAHARAN AFRICA; ADULT MALE CIRCUMCISION; SIERRA-LEONE; ANESTHESIA INFRASTRUCTURE; INCOME COUNTRIES; CATARACT-SURGERY; TRACHOMA CONTROL; HERNIA SURGERY; 21 REGIONS AB Background The perception of surgery as expensive and complex might be a barrier to its widespread acceptance in global health efforts. We did a systematic review and analysis of cost-effectiveness studies that assess surgical interventions in low-income and middle-income countries to help quantify the potential value of surgery. Methods We searched Medline for all relevant articles published between Jan 1, 1996 and Jan 31, 2013, and searched the reference lists of retrieved articles. We converted all results to 2012 US$. We extracted cost-effectiveness ratios (CERs) and appraised economic assessments for their methodological quality using the 10-point Drummond checklist. Findings Of the 584 identified studies, 26 met full inclusion criteria. Together, these studies gave 121 independent CERs in seven categories of surgical interventions. The median CER of circumcision ($13.78 per disability-adjusted life year [DALY]) was similar to that of standard vaccinations ($12.96-25.93 per DALY) and bednets for malaria prevention ($6.48-22.04 per DALY). Median CERs of cleft lip or palate repair ($47.74 per DALY), general surgery ($82.32 per DALY), hydrocephalus surgery ($108.74 per DALY), and ophthalmic surgery ($136 per DALY) were similar to that of the BCG vaccine ($51.86-220.39 per DALY). Median CERs of caesarean sections ($315.12 per DALY) and orthopaedic surgery ($381.15 per DALY) are more favourable than those of medical treatment for ischaemic heart disease ($500.41-706.54 per DALY) and HIV treatment with multidrug antiretroviral therapy ($453.74-648.20 per DALY). Interpretation Our findings suggest that many essential surgical interventions are cost-effective or very cost-effective in resource-poor countries. Quantification of the economic value of surgery provides a strong argument for the expansion of global surgery's role in the global health movement. However, economic value should not be the only argument for resource allocation-other organisational, ethical, and political arguments can also be made for its inclusion. Funding Massachusetts General Hospital Department of Surgery, Boston Children's Hospital, and Stanford University Department of Surgery. Copyright (C) Chao et al. Open Access article distributed under the terms of CC BY. C1 [Chao, Tiffany E.; Sharma, Ketan; Mandigo, Morgan; Hagander, Lars; Meara, John G.] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA USA. [Chao, Tiffany E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sharma, Ketan; Meara, John G.] Washington Univ, Sch Med, Div Plast & Reconstruct Surg, St Louis, MO USA. [Mandigo, Morgan; Meara, John G.] Boston Childrens Hosp, Dept Plast & Oral Surg, Boston, MA USA. [Mandigo, Morgan] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Hagander, Lars] Lund Univ, Dept Pediat Surg, Childrens Hosp, Lund, Sweden. [Hagander, Lars] Lund Univ, Dept Clin Sci Lund, Fac Med, Lund, Sweden. [Resch, Stephen C.] Harvard Univ, Sch Publ Hlth, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Weiser, Thomas G.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. RP Chao, TE (reprint author), 300 Longwood Ave,Enders 1, Boston, MA 02115 USA. EM tchao@partners.org FU Massachusetts General Hospital Department of Surgery FX Research support was provided to TEC by Massachusetts General Hospital Department of Surgery, to TEC, KS, MM, LH, amd JGM by Boston Children's Hospital, and to TGW by Stanford University Department of Surgery. This study forms part of the work for the forthcoming Lancet Commission on Surgery. NR 67 TC 54 Z9 55 U1 8 U2 29 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-109X J9 LANCET GLOB HEALTH JI Lancet Glob. Health PD JUN PY 2014 VL 2 IS 6 BP E334 EP E345 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AH8YW UT WOS:000336425200017 PM 25103302 ER PT J AU Krop, IE Kim, SB Gonzalez-Martin, A LoRusso, PM Ferrero, JM Smitt, M Yu, R Leung, ACF Wildiers, H AF Krop, Ian E. Kim, Sung-Bae Gonzalez-Martin, Antonio LoRusso, Patricia M. Ferrero, Jean-Marc Smitt, Melanie Yu, Ron Leung, Abraham C. F. Wildiers, Hans CA TH3RESA Study Collaborators TI Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID CLINICAL-TRIALS; PI3K PATHWAY; LAPATINIB; PROGRESSION; CAPECITABINE; COMBINATION; RESISTANCE; SURVIVAL; EFFICACY; ANTIBODY AB Background Patients with progressive disease after two or more HER2-directed regimens for recurrent or metastatic breast cancer have few effective therapeutic options. We aimed to compare trastuzumab emtansine, an antibody-drug conjugate comprising the cytotoxic agent DM1 linked to trastuzumab, with treatment of physician's choice in this population of patients. Methods This randomised, open-label, phase 3 trial took place in medical centres in 22 countries across Europe, North America, South America, and Asia-Pacific. Eligible patients (>= 18 years, left ventricular ejection fraction >= 50%, Eastern Cooperative Oncology Group performance status 0-2) with progressive HER2-positive advanced breast cancer who had received two or more HER2-directed regimens in the advanced setting, including trastuzumab and lapatinib, and previous taxane therapy in any setting, were randomly assigned (in a 2: 1 ratio) to trastuzumab emtansine (3.6 mg/kg intravenously every 21 days) or physician's choice using a permuted block randomisation scheme by an interactive voice and web response system. Patients were stratified according to world region (USA vs western Europe vs other), number of previous regimens (excluding single-agent hormonal therapy) for the treatment of advanced disease (two to three vs more than three), and presence of visceral disease (any vs none). Coprimary endpoints were investigator-assessed progression-free survival (PFS) and overall survival in the intention-to-treat population. We report the final PFS analysis and the first interim overall survival analysis. This study is registered with ClinicalTrials. gov, number NCT01419197. Findings From Sept 14, 2011, to Nov 19, 2012, 602 patients were randomly assigned (404 to trastuzumab emtansine and 198 to physician's choice). At data cutoff (Feb 11, 2013), 44 patients assigned to physician's choice had crossed over to trastuzumab emtansine. After a median follow-up of 7.2 months (IQR 5.0-10.1 months) in the trastuzumab emtansine group and 6.5 months (IQR 4.1-9.7) in the physician's choice group, 219 (54%) patients in the trastuzumab emtansine group and 129 (65%) of patients in the physician's choice group had PFS events. PFS was significantly improved with trastuzumab emtansine compared with physician's choice (median 6.2 months [95% CI 5.59-6.87] vs 3.3 months [2.89-4.14]; stratified hazard ratio [HR] 0.528 [0.422-0.661]; p<0.0001). Interim overall survival analysis showed a trend favouring trastuzumab emtansine (stratified HR 0.552 [95% CI 0.369-0.826]; p= 0.0034), but the stopping boundary was not crossed. A lower incidence of grade 3 or worse adverse events was reported with trastuzumab emtansine than with physician's choice (130 events [32%] in 403 patients vs 80 events [43%] in 184 patients). Neutropenia (ten [2%] vs 29 [16%]), diarrhoea (three [<1%] vs eight [4%]), and febrile neutropenia (one [<1%] vs seven [4%]) were grade 3 or worse adverse events that were more common in the physician's choice group than in the trastuzumab emtansine group. Thrombocytopenia (19 [5%] vs three [2%]) was the grade 3 or worse adverse event that was more common in the trastuzumab emtansine group. 74 (18%) patients in the trastuzumab emtansine group and 38 (21%) in the physician's choice group reported a serious adverse event. Interpretation Trastuzumab emtansine should be considered as a new standard for patients with HER2-positive advanced breast cancer who have previously received trastuzumab and lapatinib. C1 [Krop, Ian E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Sung-Bae] Univ Ulsan, Asan Med Ctr, Coll Med, Seoul, South Korea. [Gonzalez-Martin, Antonio] MD Anderson Canc Ctr, Madrid, Spain. [LoRusso, Patricia M.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Ferrero, Jean-Marc] Ctr Antoine Lacassagne, Dept Med Oncol, F-06054 Nice, France. [Smitt, Melanie; Yu, Ron; Leung, Abraham C. F.] Genentech Inc, San Francisco, CA 94080 USA. [Wildiers, Hans] Univ Hosp Leuven, Dept Gen Med Oncol, Louvain, Belgium. RP Krop, IE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM ikrop@partners.org FU Genentech FX Genentech. NR 31 TC 118 Z9 119 U1 2 U2 18 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 JUN PY 2014 VL 15 IS 7 BP 689 EP 699 DI 10.1016/S1470-2045(14)70178-0 PG 11 WC Oncology SC Oncology GA AH9ZR UT WOS:000336505900037 PM 24793816 ER PT J AU Fan, L Strasser-Weippl, K Li, JJ St Louis, J Finkelstein, DM Yu, KD Chen, WQ Shao, ZM Goss, PE AF Fan, Lei Strasser-Weippl, Kathrin Li, Jun-Jie St Louis, Jessica Finkelstein, Dianne M. Yu, Ke-Da Chen, Wan-Qing Shao, Zhi-Ming Goss, Paul E. TI Breast cancer in China SO LANCET ONCOLOGY LA English DT Review ID MIDDLE-INCOME COUNTRIES; PERIOD-COHORT ANALYSIS; SELF-EXAMINATION; RECEPTOR STATUS; RISK-FACTORS; COST-EFFECTIVENESS; ESTROGEN-RECEPTOR; LATIN-AMERICA; BODY-SIZE; HONG-KONG AB The health burden of cancer is increasing in China, with more than 1 . 6 million people being diagnosed and 1 . 2 million people dying of the disease each year. As in most other countries, breast cancer is now the most common cancer in Chinese women; cases in China account for 12 . 2% of all newly diagnosed breast cancers and 9 . 6% of all deaths from breast cancer worldwide. China's proportional contribution to global rates is increasing rapidly because of the population's rising socioeconomic status and unique reproductive patterns. In this Review we present an overview of present control measures for breast cancer across China, and emphasise epidemiological and socioeconomic diversities and disparities in access to care for various subpopulations. We describe demographic differences between China and high-income countries, and also within geographical and socioeconomic regions of China. These disparities between China and high-income countries include younger age at onset of breast cancer; the unique one-child policy; lower rates of provision and uptake for screening for breast cancer; delays in diagnosis that result in more advanced stage of disease at presentation; inadequate resources; and a lack of awareness about breast cancer in the Chinese population. Finally, we recommend key measures that could contribute to improved health outcomes for patients with breast cancer in China. C1 [Fan, Lei; Strasser-Weippl, Kathrin; Li, Jun-Jie; St Louis, Jessica; Goss, Paul E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Int Breast Canc Program, Boston, MA USA. [Finkelstein, Dianne M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Fan, Lei; Li, Jun-Jie; Yu, Ke-Da; Shao, Zhi-Ming] Fudan Univ, Dept Breast Surg, Ctr Canc, Shanghai 200433, Peoples R China. [Fan, Lei; Li, Jun-Jie; Yu, Ke-Da; Shao, Zhi-Ming] Fudan Univ, Inst Canc, Shanghai 200433, Peoples R China. [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol Hematol & Palliat Care, Vienna, Austria. [Chen, Wan-Qing] Chinese Acad Med Sci, Natl Off Canc Prevent & Control, Beijing 100730, Peoples R China. RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Lawrence House,LRH 302, Boston, MA 02114 USA. EM pgoss@partners.org FU Avon Foundation New York FX PEG, LF, J-JL, JSL, and DMF are supported by The Avon Foundation New York. This funding source had no role in the planning or writing of the Review. NR 117 TC 161 Z9 233 U1 25 U2 108 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 JUN PY 2014 VL 15 IS 7 BP E279 EP E289 PG 11 WC Oncology SC Oncology GA AH9ZR UT WOS:000336505900023 PM 24872111 ER PT J AU Spiegel, P Khalifa, A Mateen, FJ AF Spiegel, Paul Khalifa, Adam Mateen, Farrah J. TI Cancer in refugees in Jordan and Syria between 2009 and 2012: challenges and the way forward in humanitarian emergencies SO LANCET ONCOLOGY LA English DT Review ID AFGHAN REFUGEES; HEALTH AB Treatment of non-communicable diseases such as cancer in refugees is neglected in low-income and middle-income countries, but is of increasing importance because the number of refugees is growing. The UNHCR, through exceptional care committees (ECCs), has developed standard operating procedures to address expensive medical treatment for refugees in host countries, to decide on eligibility and amount of payment. We present data from funding applications for cancer treatments for refugees in Jordan between 2010 and 2012, and in Syria between 2009 and 2011. Cancer in refugees causes a substantial burden on the health systems of the host countries. Recommendations to improve prevention and treatment include improvement of health systems through standard operating procedures and innovative financing schemes, balance of primary and emergency care with expensive referral care, development of electronic cancer registries, and securement of sustainable funding sources. Analysis of cancer care in low-income refugee settings, particularly in sub-Saharan Africa, is needed to inform future responses. C1 [Spiegel, Paul] Off United Nations High Commissioner Refugees, CH-1211 Geneva, Switzerland. [Khalifa, Adam] Off United Nations High Commissioner Refugees, Damascus, Syria. [Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA USA. RP Spiegel, P (reprint author), Off United Nations High Commissioner Refugees, CH-1211 Geneva, Switzerland. EM spiegel@unhcr.org NR 18 TC 10 Z9 10 U1 1 U2 13 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 JUN PY 2014 VL 15 IS 7 BP E290 EP E297 PG 8 WC Oncology SC Oncology GA AH9ZR UT WOS:000336505900024 PM 24872112 ER PT J AU Decramer, M Anzueto, A Kerwin, E Kaelin, T Richard, N Crater, G Tabberer, M Harris, S Church, A AF Decramer, Marc Anzueto, Antonio Kerwin, Edward Kaelin, Thomas Richard, Nathalie Crater, Glenn Tabberer, Maggie Harris, Stephanie Church, Alison TI Efficacy and safety of umeclidinium plus vilanterol versus tiotropium, vilanterol, or umeclidinium monotherapies over 24 weeks in patients with chronic obstructive pulmonary disease: results from two multicentre, blinded, randomised controlled trials SO LANCET RESPIRATORY MEDICINE LA English DT Article ID REFERENCE VALUES; COPD PATIENTS; DYSPNEA; SALMETEROL; BRONCHODILATION; QUESTIONNAIRE; INDACATEROL; SHORTNESS; SAMPLE; BREATH AB Background Combination long-acting bronchodilator treatment might be more effective than long-acting bronchodilator monotherapy for the treatment of chronic obstructive pulmonary disease (COPD). We aimed to compare the efficacy and safety of umeclidinium (UMEC) plus vilanterol (VI) with tiotropium (TIO) monotherapy, UMEC monotherapy, or VI monotherapy in patients with moderate to very severe COPD. Methods In two multicentre, randomised, blinded, double-dummy, parallel-group, active-controlled trials, eligible patients (current or former smokers aged 40 years or older with an established clinical history of COPD) were randomly assigned in 1:1:1:1 ratio to UMEC 125 mu g plus VI 25 mu g, UMEC 62.5 mu g plus VI 25 mu g, TIO 18 mu g, and either VI 25 mu g (study 1) or UMEC 125 mu g (study 2). All study drugs were used once daily for 24 weeks. TIO was delivered via the HandiHaler inhaler and all other active treatments were delivered via the ELLIPTA dry powder inhaler. Random assignment (by a validated computer-based system) was done by centre and was not stratified. All patients and physicians were masked to assigned treatment during the studies. The primary efficacy endpoint of both studies was trough forced expiratory volume in 1 s (FEV1) on day 169, which was analysed in the intention-to-treat population. Both studies are registered with ClinicalTrials.gov, numbers NCT01316900 (study 1) and NCT01316913 (study 2). Findings 1141 participants were recruited in study 1, and 1191 in study 2. For study 1, after exclusions, 208, 209, 214, and 212 patients were included in the intention-to-treat analyses for TIO monotherapy, VI monotherapy, UMEC 125 mu g plus VI 25 mu g, and UMEC 62.5 mu g plus VI 25 mu g, respectively. For study 2, 215, 222, 215, and 217 patients were included in the intention-to-treat analyses for TIO monotherapy, UMEC monotherapy, UMEC 125 mu g plus VI 25 mu g, and UMEC 62.5 mu g plus VI 25 mu g, respectively. In both studies, we noted improvements in trough FEV1 on day 169 for both doses of UMEC plus VI compared with TIO monotherapy (study 1, UMEC 125 mu g plus VI 25 mu g: 0.088 L [95% CI 0.036 to 0.140; p=0.0010]; study 1, UMEC 62.5 mu g plus VI 25 mu g: 0.090 L [0.039 to 0.141; p=0.0006]; study 2, UMEC 125 mu g plus VI 25 mu g: 0.074 L [0.025 to 0.123; p=0.0031]; study 2, UMEC 62.5 mu g plus VI 25 mu g: 0.060 L [0.010 to 0.109; nominal p=0.0182]). Both doses of UMEC plus VI also improved trough FEV1 compared with VI monotherapy (UMEC 125 mu g plus VI 25 mu g: 0.088 L [0.036 to 0.140; p=0.0010]; UMEC 62.5 mu g plus VI 25 mu g: 0.090 L [0.039 to 0.142; p=0.0006], but not compared with UMEC 125 mu g monotherapy (UMEC 125 mu g plus VI 25 mu g: 0.037 L [-0.012 to 0.087; p=0.14]; UMEC 62.5 mu g plus VI 25 mu g: 0.022 L [-0.027 to 0.072; p=0.38]). All treatments produced improvements in dyspnoea and health-related quality of life; we noted no significant differences in symptoms, health status, or risk of exacerbation between UMEC plus VI and TIO. The most common on-treatment, severe-intensity adverse event in both studies was acute exacerbation of COPD (1-4 [<1-2%] patients across treatment groups in study 1 and 1-6 [<1-3%] patients in study 2). We recorded five to 15 (2-7%) on-treatment serious adverse events across treatment groups in study 1, and nine to 22 (4-10%) in study 2. We noted no substantial changes from baseline in vital signs, clinical laboratory findings, or electrocardiography findings in any of the treatment groups. Interpretation Combination treatment with once-daily UMEC plus VI improved lung function compared with VI monotherapy and TIO monotherapy in patients with COPD. Overall our results suggest that the combination of UMEC plus VI could be beneficial for the treatment of moderate to very severe COPD. C1 [Decramer, Marc] Univ Louvain, Div Resp, Univ Hosp, B-3000 Louvain, Belgium. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Kerwin, Edward] Clin Res Inst Southern Oregon, Medford, OR USA. [Kaelin, Thomas] Lowcountry Lung & Crit Care, Charleston, SC USA. [Richard, Nathalie; Harris, Stephanie; Church, Alison] GlaxoSmithKline, Resp & Immunoinflammat, Res Triangle Pk, NC USA. [Crater, Glenn] Aerocrine, Clin Dev, Morrisville, NC USA. [Tabberer, Maggie] GlaxoSmithKline, Uxbridge, Middx, England. RP Decramer, M (reprint author), Univ Louvain, Div Resp, Univ Hosp, B-3000 Louvain, Belgium. EM marc.decramer@uzleuven.be OI Crater, Glenn/0000-0002-1159-1323 FU GlaxoSmithKline FX The work presented here, including the conduct of the study, data analysis, and data interpretation, was supported by GlaxoSmithKline. Editorial assistance in the preparation of the report was provided by David Griffiths (Fishawack Indicia, Knutsford, UK) and was funded by GlaxoSmithKline. NR 34 TC 88 Z9 89 U1 0 U2 14 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 JUN PY 2014 VL 2 IS 6 BP 472 EP 486 DI 10.1016/S2213-2600(14)70065-7 PG 15 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA AI2WA UT WOS:000336717900018 PM 24835833 ER PT J AU Brault, M Ray, J Gomez, YH Mantzoros, CS Daskalopoulou, SS AF Brault, Marilyne Ray, Jessica Gomez, Yessica-Haydee Mantzoros, Christos S. Daskalopoulou, Stella S. TI Statin treatment and new-onset diabetes: A review of proposed mechanisms SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Review DE HMG-CoA inhibitors; Diabetes mellitus; Lipophilicity; Adipocytes; Adiponectin; GLUT4; Isoprenoids; Ca2+ channels; Cholesterol ID PANCREATIC BETA-CELLS; COA REDUCTASE INHIBITORS; CORONARY-ARTERY-DISEASE; INSULIN-SECRETION; PPAR-GAMMA; DRUG-INTERACTIONS; GLUCOSE-UPTAKE; CHOLESTEROL ACCUMULATION; NONDIABETIC PATIENTS; PROTEIN PRENYLATION AB New-onset diabetes has been observed in clinical trials and meta-analyses involving statin therapy. To explain this association, three major mechanisms have been proposed and discussed in the literature. First, certain statins affect insulin secretion through direct, indirect Or combined effects on calcium channels in pancreatic (beta-cells. Second, reduced translocation of glucose transporter 4 in response to treatment results in hyperglycemia and hyperinsulinemia. Third, statin therapy decreases other important downstream products, such as coenzyme Q10, farnesyl pyrophosphate, geranylgeranyl pyrophosphate, and dolichol; their depletion leads to reduced intracellular signaling. Other possible mechanisms implicated in the effect of statins on new-onset diabetes are: statin interference with intracellular insulin signal transduction pathways via inhibition of necessary phosphorylation events and reduction of small GTPase action; inhibition of adipocyte differentiation leading to decreased peroxisome proliferator activated receptor gamma and CCAAT/enhancer-binding protein which are important pathways for glucose homeostasis; decreased leptin causing inhibition of (beta-cells proliferation and insulin secretion; and diminished adiponectin levels. Given that the magnitude of the risk of new-onset diabetes following statin use remains to be fully clarified and the well-established beneficial effect of statins in reducing cardiovascular risk, statins remain the first-choice treatment for prevention of CVD. Elucidation of the mechanisms underlying the development of diabetes in association with statin use may help identify novel preventative or therapeutic approaches to this problem and/or help design a new generation statin without such side-effects. (C) 2014 Elsevier Inc. All rights reserved. C1 [Brault, Marilyne] McGill Univ, Fac Med, Dept Med, Montreal, PQ H3G 1A4, Canada. [Ray, Jessica] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3G 1A4, Canada. [Gomez, Yessica-Haydee; Daskalopoulou, Stella S.] McGill Univ, Fac Med, Div Internal Med, Dept Med, Montreal, PQ H3G 1A4, Canada. [Mantzoros, Christos S.] VA Boston Healthcare Syst, Endocrinol Sect, Boston, MA USA. [Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Daskalopoulou, Stella S.] McGill Univ, Fac Med, Div Expt Med, Dept Med, Montreal, PQ H3G 1A4, Canada. RP Daskalopoulou, SS (reprint author), McGill Univ, Ctr Hlth, Div Internal Med, Dept Med, 1650 Cedar Ave,C2-101-4, Montreal, PQ H3G 1A4, Canada. EM stella.daskalopoulou@mcgill.ca NR 98 TC 46 Z9 49 U1 2 U2 23 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 JUN PY 2014 VL 63 IS 6 BP 735 EP 745 DI 10.1016/j.metabol.2014.02.014 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI1UH UT WOS:000336640100001 PM 24641882 ER PT J AU Hwang, JJ Thakkar, B Chamberland, JP Mantzoros, CS AF Hwang, Janice J. Thakkar, Bindiya Chamberland, John P. Mantzoros, Christos S. TI Circulating fetuin-A levels are not affected by short and long-term energy deprivation and/or by leptin administration SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Fetuin-A; Leptin; Alpha-2-Heremans-Schmid glycoprotein ID HYPOTHALAMIC AMENORRHEA; METABOLIC SYNDROME; HEALTHY-MEN; WOMEN; HUMANS; RISK; NEUROENDOCRINE; HYPOLEPTINEMIA AB Objective. Fetuin-A may mediate cross-talk between the liver and adipose tissue. We studied the physiologic regulation of fetuin-A and explored its potential regulation by leptin. Design and Methods. Fetuin-A levels were measured in three interventional studies as well as in in vitro experiments. Study 1: 15 lean subjects received placebo or physiologic replacement-dose recombinant human leptin (metreleptin) following short term complete caloric deprivation to induce severe hypoleptinemia; Study 2: 7 women with relative leptin deficiency due to strenuous exercise or low weight received 3 months of metreleptin; Study 3: 17 women with relative leptin deficiency were randomized to receive metreleptin or placebo over 9 months. In study 4 human hepatoma Hep G2 cells were treated with leptin. Fetuin-A mRNA expression and secretion were measured. Results. Complete caloric deprivation significantly decreased leptin but had no effect on fetuin-A levels. Normalizing leptin levels with metreleptin in hypoleptinemic subjects had no effect on circulating fetuin-A levels. Leptin treatment had no effect on fetuin-A mRNA expression and secretion in vitro. Conclusions. Circulating fetuin-A levels are not affected by short and long-term energy deprivation. Furthermore, both in vivo and in vitro experiments confirm that fetuin-A is not regulated by leptin. Published by Elsevier Inc. C1 [Hwang, Janice J.; Thakkar, Bindiya; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Med, Boston, MA 02130 USA. [Thakkar, Bindiya; Chamberland, John P.] Harvard Univ, Boston VA Healthcare Syst, Sch Med, Endocrinol Sect, Boston, MA USA. [Thakkar, Bindiya; Mantzoros, Christos S.] Boston Univ, Sch Med, Boston Med Ctr, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. RP Thakkar, B (reprint author), Div Endocrinol Diabet & Metab, 150 S Huntington Ave,9B-52A, Boston, MA 02130 USA. EM Bindiya.Thakkar@bmc.org FU Harvard Clinical and Translational Science Center [L1 RR025758, M01-RR-01032] FX The project described was supported by Grant Number UL1 RR025758 and M01-RR-01032 Harvard Clinical and Translational Science Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional support for this research came from grant-in-aid by Tanita Corporation and from Amgen/Amylin to BIDMC. Amylin Pharmaceuticals, LLC (a wholly-owned subsidiary of Bristol-Myers Squibb) supplied metreleptin for this study but had no role in the study design; conduct of the study; collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 29 TC 3 Z9 3 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JUN PY 2014 VL 63 IS 6 BP 754 EP 759 DI 10.1016/j.metabol.2014.02.006 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI1UH UT WOS:000336640100003 PM 24703486 ER PT J AU Aronis, KN Sahin-Efe, A Chamberland, JP Spiro, A Vokonas, P Mantzoros, CS AF Aronis, Konstantinos N. Sahin-Efe, Ayse Chamberland, John P. Spiro, Avron, III Vokonas, Pantel Mantzoros, Christos S. TI Chemerin levels as predictor of acute coronary events: A case-control study nested within the veterans affairs normative aging study SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Chemerin; Acute Coronary Events; Normative Aging Study ID EPICARDIAL ADIPOSE-TISSUE; MESSENGER-RNA EXPRESSION; FATTY LIVER-DISEASE; METABOLIC SYNDROME; ARTERY-DISEASE; INSULIN-RESISTANCE; BARIATRIC SURGERY; RECEPTOR CHEMR23; WEIGHT-LOSS; OBESITY AB Objective. Chemerin is a recently identified adipocytokine that has been positively correlated with the presence and severity of coronary artery disease (CAD). However, no studies have examined circulating chemerin levels as a predictor of acute coronary syndrome (ACS). The purpose of this study is to evaluate whether chemerin levels predict the onset of ACS. Materials/Methods. We studied 90 men whose serum had been collected at least 2 years before the development of ACS, and 162 controls matched with the cases in a 1:2 fashion for age and year of collection. The mean age of the cohort was 66.3 +/- 9.6 years (range 34-84 years). Serum chemerin levels were measured with a commercially available enzyme-linked immunosorbent assay. Results. Age was positively associated with chemerin levels (r = 0.39, p < 0.001). Logistic regression analysis, adjusting for years since blood collection, demonstrated a null association between chemerin levels and the odds ratio for development of ACS (OR: 0.99, 95% CI [0.99-1.001]). This association remained null after adjusting for age (OR: 0.99 95% CI [0.99-1.001]). Conclusions. Although cross-sectional and case control studies suggest a positive association between chemerin levels and CAD, we demonstrate that chemerin levels do not predict the development of ACS. (C) 2014 Elsevier Inc. All rights reserved. C1 [Aronis, Konstantinos N.; Sahin-Efe, Ayse; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Endocrinol Sect, Cambridge, MA 02138 USA. [Aronis, Konstantinos N.; Sahin-Efe, Ayse; Chamberland, John P.; Mantzoros, Christos S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab,Dept Med, Cambridge, MA 02138 USA. [Aronis, Konstantinos N.; Mantzoros, Christos S.] Boston Univ, Sch Med, Boston Med Ctr, Dept Med, Boston, MA 02215 USA. [Spiro, Avron, III; Vokonas, Pantel] VA Boston Healthcare Syst, Normat Aging Study, Jamaica Plain, MA USA. [Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Spiro, Avron, III; Vokonas, Pantel] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Aronis, KN (reprint author), VA Boston Hlth Care Syst, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA. EM konstantinos.aronis@bmc.org RI Aronis, Konstantinos/F-3586-2012 OI Aronis, Konstantinos/0000-0001-7189-8434 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; Massachusetts Veterans Epidemiology Research and Information Center; Research Career Scientist award from the Clinical Science Research and Development Service, US Department of Veterans' Affairs FX The Mantzoros Laboratory is supported by the 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. NR 51 TC 6 Z9 6 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 JUN PY 2014 VL 63 IS 6 BP 760 EP 766 DI 10.1016/j.metabol.2014.02.013 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI1UH UT WOS:000336640100004 PM 24684821 ER PT J AU Liu, X Hamnvik, OPR Chamberland, JP Petrou, M Gong, H Christophi, CA Christiani, DC Kales, SN Mantzoros, CS AF Liu, Xiaowen Hamnvik, Ole-Petter R. Chamberland, John P. Petrou, Michael Gong, Huizhi Christophi, Costas A. Christiani, David C. Kales, Stefanos N. Mantzoros, Christos S. TI Circulating alanine transaminase (ALT) and gamma-glutamyl transferase (GGT), but not fetuin-A, are associated with metabolic risk factors, at baseline and at two-year follow-up: The prospective Cyprus Metabolism Study SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Obesity; Insulin resistance; Metabolic syndrome ID MIDDLE-AGED MEN; TYPE-2 DIABETES-MELLITUS; INSULIN-RESISTANCE; SERUM FETUIN; LIVER-ENZYMES; JAPANESE MEN; OBESITY; AMINOTRANSFERASE; DISEASE; WOMEN AB Objective. To comparatively evaluate traditional liver tests and fetuin A as predictors of cardiometabolic risk, we studied associations between serum alanine transaminase (ALT), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and fetuin-A and anthropometric, metabolic, and cardiovascular parameters cross-sectionally at baseline, and prospectively, after 2-years of follow-up. Research Design and Methods. 616 randomly enrolled young healthy participants in the Cyprus Metabolism Study, including all 93 subjects who participated in the follow-up study 2 years after baseline assessment, were included in this study. Results. In the cross-sectional study, serum ALT and GGT were strongly correlated with anthropometric, cardiovascular, and metabolic variables, while serum AST was only correlated with waist circumference and waist-to-hip ratio. Fetuin-A was correlated with anthropometric variables, systolic blood pressure (SBP), insulin, and homeostasis model of assessment-insulin resistance (HOMA-IR) in the unadjusted model. In the fully adjusted model, both serum ALT and GGT levels remained positively correlated with total and low-density lipoprotein (LDL) cholesterol. GGT levels also remained correlated with triglycerides. ALT levels remained strongly positively correlated with insulin (r = 0.17, p < .0001) and HOMA-IR (r = 0.16, p = 0.0001). Serum fetuin-A levels were no longer significantly correlated with any variables. Prospectively, ALT and GGT were predictors of anthropometric variables and LDL cholesterol, while baseline levels of AST and fetuin-A were not predictors of any variables at 2-year follow-up. Conclusions. We confirmed associations of ALT and GGT levels but failed to demonstrate an independent association between fetuin-A and cardiometabolic risk factors in young healthy men. Traditional liver tests (LFTs) are thus better than fetuin-A predictors of metabolic risk factors cross-sectionally and prospectively in young healthy adults. (C) 2014 Elsevier Inc. All rights reserved. C1 [Liu, Xiaowen; Chamberland, John P.; Gong, Huizhi; Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Liu, Xiaowen; Hamnvik, Ole-Petter R.; Chamberland, John P.; Gong, Huizhi; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston, MA USA. [Hamnvik, Ole-Petter R.; Mantzoros, Christos S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Petrou, Michael; Christophi, Costas A.] Cyprus Univ Technol, Harvard Sch Publ Hlth, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus. [Christophi, Costas A.; Christiani, David C.; Kales, Stefanos N.; Mantzoros, Christos S.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02139 USA. [Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. RP Kales, SN (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Macth Bldg 427,1493 Cambridge St, Cambridge, MA 02139 USA. EM skales@hsph.harvard.edu RI Hamnvik, Ole-Petter/D-1719-2011 FU Cyprus Research Promotion Foundation [EPE/0205/10]; Beth Israel Deaconess Medical Center [DK58785, DK79929, DK81913, AG032030]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University FX The study was supported by the Cyprus Research Promotion Foundation (EP Upsilon E Xi/0205/10). The Mantzoros Lab is supported by grants DK58785, DK79929, DK81913, AG032030, a VA Merit award and a discretionary grant from Beth Israel Deaconess Medical Center. This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). NR 47 TC 13 Z9 13 U1 0 U2 9 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 JUN PY 2014 VL 63 IS 6 BP 773 EP 782 DI 10.1016/j.metabol.2014.03.008 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AI1UH UT WOS:000336640100006 PM 24726813 ER PT J AU Forristal, C Henley, SA MacDonald, JI Bush, JR Ort, C Passos, DT Talluri, S Ishak, CA Thwaites, MJ Norley, CJ Litovchick, L DeCaprio, JA DiMattia, G Holdsworth, DW Beier, F Dick, FA AF Forristal, Chantal Henley, Shauna A. MacDonald, James I. Bush, Jason R. Ort, Carley Passos, Daniel T. Talluri, Srikanth Ishak, Charles A. Thwaites, Michael J. Norley, Chris J. Litovchick, Larisa DeCaprio, James A. DiMattia, Gabriel Holdsworth, David W. Beier, Frank Dick, Frederick A. TI Loss of the Mammalian DREAM Complex Deregulates Chondrocyte Proliferation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE; GENE-EXPRESSION; B-MYB; RETINOBLASTOMA PROTEIN; HISTONE DEACETYLASE; IN-VIVO; REPRESS TRANSCRIPTION; TARGETED DISRUPTION; G(2)/M GENES; MICE LACKING AB Mammalian DREAM is a conserved protein complex that functions in cellular quiescence. DREAM contains an E2F, a retinoblastoma (RB)-family protein, and the MuvB core (LIN9, LIN37, LIN52, LIN54, and RBBP4). In mammals, MuvB can alternatively bind to BMYB to form a complex that promotes mitotic gene expression. Because BMYB-MuvB is essential for proliferation, loss-of-function approaches to study MuvB have generated limited insight into DREAM function. Here, we report a gene-targeted mouse model that is uniquely deficient for DREAM complex assembly. We have targeted p107 (Rbl1) to prevent MuvB binding and combined it with deficiency for p130 (Rbl2). Our data demonstrate that cells from these mice preferentially assemble BMYB-MuvB complexes and fail to repress transcription. DREAM-deficient mice show defects in endochondral bone formation and die shortly after birth. Micro-computed tomography and histology demonstrate that in the absence of DREAM, chondrocytes fail to arrest proliferation. Since DREAM requires DYRK1A (dual-specificity tyrosine phosphorylation-regulated protein kinase 1A) phosphorylation of LIN52 for assembly, we utilized an embryonic bone culture system and pharmacologic inhibition of (DYRK) kinase to demonstrate a similar defect in endochondral bone growth. This reveals that assembly of mammalian DREAM is required to induce cell cycle exit in chondrocytes. C1 [Forristal, Chantal; Henley, Shauna A.; MacDonald, James I.; Passos, Daniel T.; Talluri, Srikanth; Ishak, Charles A.; Thwaites, Michael J.; DiMattia, Gabriel; Dick, Frederick A.] Univ Western Ontario, London Reg Canc Program, London, ON, Canada. [Bush, Jason R.; Beier, Frank; Dick, Frederick A.] Univ Western Ontario, Childrens Hlth Res Inst, London, ON, Canada. [Forristal, Chantal; Henley, Shauna A.; MacDonald, James I.; Passos, Daniel T.; Talluri, Srikanth; Ishak, Charles A.; Thwaites, Michael J.; DiMattia, Gabriel; Dick, Frederick A.] Univ Western Ontario, Dept Biochem, London, ON, Canada. [Bush, Jason R.; Beier, Frank] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON, Canada. [Norley, Chris J.; Holdsworth, David W.] Univ Western Ontario, Dept Med Biophys, London, ON, Canada. [DiMattia, Gabriel; Dick, Frederick A.] Univ Western Ontario, Dept Oncol, London, ON, Canada. [Litovchick, Larisa] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA. [DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [DeCaprio, James A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Dick, FA (reprint author), Univ Western Ontario, London Reg Canc Program, London, ON, Canada. EM fdick@uwo.ca RI Passos, Daniel/K-5520-2012; Holdsworth, David/F-6315-2012; Beier, Frank/G-4595-2013 OI Passos, Daniel/0000-0002-3530-2821; Beier, Frank/0000-0002-8505-7537 FU SRP award from the Schulich School of Medicine and Dentistry; CaRTT; CBCF-Ontario; Canadian Cancer Society Research Institute [2011700720]; Canadian Institutes of Health Research [MOP43899]; CIHR postdoctoral fellowship (Priority Announcement: Epigenetics) FX C.F. was supported by an SRP award from the Schulich School of Medicine and Dentistry. S.A.H. and C.A.I. were supported by fellowship awards from CaRTT, and S.A.H. also acknowledges fellowship support from CBCF-Ontario. J.R.B. is the recipient of CIHR postdoctoral fellowship (Priority Announcement: Epigenetics). F.B. is the Canada Research Chair in musculoskeletal research. F.A.D. is the Wolfe Senior Fellow in Tumor Suppressor Genes at Western University. Funding for this work was provided by the Canadian Cancer Society Research Institute (2011700720) to F.A.D. and the Canadian Institutes of Health Research (MOP43899) to F.B. NR 57 TC 7 Z9 8 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2014 VL 34 IS 12 BP 2221 EP 2234 DI 10.1128/MCB.01523-13 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AI3EQ UT WOS:000336743200010 PM 24710275 ER PT J AU Panic, N Mastrostefano, E Leoncini, E Persiani, R Arzani, D Amore, R Ricci, R Sicoli, F Sioletic, S Bulajic, M D' Ugo, D Ricciardi, W Boccia, S AF Panic, Nikola Mastrostefano, Elena Leoncini, Emanuele Persiani, Roberto Arzani, Dario Amore, Rosarita Ricci, Riccardo Sicoli, Federico Sioletic, Stefano Bulajic, Milutin D' Ugo, Domenico Ricciardi, Walter Boccia, Stefania TI Susceptibility to Helicobacter pylori infection: results of an epidemiological investigation among gastric cancer patients SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE Helicobacter pylori; Gastric cancer; Genetic polymorphism; Family history ID METHYLENETETRAHYDROFOLATE REDUCTASE C677T; P53 ARG72PRO POLYMORPHISM; CARDIOVASCULAR EVENTS; A1298C POLYMORPHISMS; ALCOHOL-CONSUMPTION; ITALIAN POPULATION; GENE POLYMORPHISMS; ALLELE FREQUENCIES; MULTIPLEX PCR; RISK-FACTORS AB The aim of this study was to identify the clinical, demographic, lifestyle factors and selected genetic polymorphisms that affect the susceptibility towards Helicobacter pylori (H. pylori) infection in gastric cancer patients. Histological confirmed gastric adenocarcinoma cases that underwent curative gastrectomy between 2002 and 2012 were included. Gastric biopsy samples were obtained to determine the H. pylori status, and further cagA status and vacA m and s genotypes by polymerase chain reaction. Patients were interviewed with structured questionnaires, and blood samples were collected for EPHX1, GSTM1, GSTT1, IL1B, IL1-RN, MTHFR and p53 genotyping. Proportions were compared in univariate analysis, while the relation between putative risk factors and H. pylori status and genotype were measured using logistic regression analysis. One hundred forty-nine gastric cancer patients were included, of which 78.5 % were H. pylori positive. Among positive patients 50 % were cagA+, 72.5 % vacA m1 and 80.7 % vacA s1. The presence of cagA was less frequent among vacA m1 (p = 0.031) and vacA s1 (p = 0.052) subtypes. The presence of father history for any cancer was a significant risk factor for H. pylori infection [adjusted odds ratio (OR) = 8.18, 95 % confidence interval (CI) 1.04-64.55]. EPHX1 exon 3 T > C (OR = 0.35, CI 95 % 0.13-0.94), IL1B-511 T > C (OR = 0.38, CI 95 % 0.15-0.97) and IL1-RN VNTR (OR = 0.19, CI 95 % 0.06-0.58) polymorphisms were protective towards H. pylori infection in the univariate analysis. Wine consumption was associated with higher risk of carrying the H. pylori vacA m1 virulent subtype (p = 0.034). Lastly, cardiovascular diseases were less common among cagA positive subjects (p = 0.023). Father history of any cancer is a risk factor for H. pylori infection. Polymorphisms in IL1B-511, IL1-RN and EPHX1 exon 3 genes might be protective towards H. pylori infection. C1 [Panic, Nikola; Mastrostefano, Elena; Leoncini, Emanuele; Arzani, Dario; Amore, Rosarita; Ricciardi, Walter; Boccia, Stefania] Univ Cattolica Sacro Cuore, Sect Hyg, Inst Publ Hlth, Rome, Italy. [Panic, Nikola; Bulajic, Milutin] Univ Belgrade, Fac Med, Belgrade, Serbia. [Panic, Nikola; Bulajic, Milutin] Univ Clin Hosp Ctr Dr DragisaMisovic Dedinje, Belgrade, Serbia. [Persiani, Roberto; Sicoli, Federico; D' Ugo, Domenico] Univ Cattolica Sacro Cuore, Dept Surg, Rome, Italy. [Ricci, Riccardo] Univ Cattolica Sacro Cuore, Dept Pathol, Rome, Italy. [Sioletic, Stefano] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. [Bulajic, Milutin] Univ Clin Hosp Santa Maria della Misericordia, Udine, Italy. [Boccia, Stefania] IRCCS San Raffaele, Rome, Italy. RP Boccia, S (reprint author), Univ Cattolica Sacro Cuore, Sect Hyg, Inst Publ Hlth, Rome, Italy. EM sboccia@rm.unicatt.it RI Kim, Seongman/N-6910-2014; Ricci, Riccardo/E-4411-2010; Ricci, Riccardo/A-8195-2017; , emanuele/A-5466-2010 OI Ricci, Riccardo/0000-0002-9089-5084; Ricci, Riccardo/0000-0002-9089-5084; , emanuele/0000-0002-7669-8535 FU AIRC (Associazione Italiana Ricerca sul Cancro) [IG 2013 N.14220]; Italian Ministry of Health [GR-2011-02347943]; ERAWEB project; European Community; Fondazione Veronesi FX This work has been supported by the AIRC (Associazione Italiana Ricerca sul Cancro) IG 2013 N.14220, and from the Italian Ministry of Health (GR-2011-02347943). The work of Dr Nikola Panic was supported by the ERAWEB project, funded with support of the European Community. The work of Dr Emanuele Leoncini was supported by Fondazione Veronesi. NR 61 TC 3 Z9 3 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-4851 EI 1573-4978 J9 MOL BIOL REP JI Mol. Biol. Rep. PD JUN PY 2014 VL 41 IS 6 BP 3637 EP 3650 DI 10.1007/s11033-014-3228-0 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AH8QY UT WOS:000336404500012 PM 24526578 ER PT J AU Hooli, BV Kovacs-Vajna, ZM Mullin, K Blumenthal, MA Mattheisen, M Zhang, C Lange, C Mohapatra, G Bertram, L Tanzi, RE AF Hooli, B. V. Kovacs-Vajna, Z. M. Mullin, K. Blumenthal, M. A. Mattheisen, M. Zhang, C. Lange, C. Mohapatra, G. Bertram, L. Tanzi, R. E. TI Rare autosomal copy number variations in early-onset familial Alzheimer's disease SO MOLECULAR PSYCHIATRY LA English DT Article DE Alzheimer's; CNVs; MAPT; CHMP2B; VLDLR ID COMPARATIVE GENOMIC HYBRIDIZATION; N-CADHERIN; MENTAL-RETARDATION; DE-NOVO; GRANULOVACUOLAR DEGENERATION; FRONTOTEMPORAL DEMENTIA; STRUCTURAL VARIATION; ASSOCIATION ANALYSIS; GENETIC ASSOCIATION; LOCUS DUPLICATION AB Over 200 rare and fully penetrant pathogenic mutations in amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2) cause a subset of early-onset familial Alzheimer's disease (EO-FAD). Of these, 21 cases of EO-FAD families carrying unique APP locus duplications remain the only pathogenic copy number variations (CNVs) identified to date in Alzheimer's disease (AD). Using highdensity DNA microarrays, we performed a comprehensive genome-wide analysis for the presence of rare CNVs in 261 EO-FAD and early/mixed-onset pedigrees. Our analysis revealed 10 novel private CNVs in 10 EO-FAD families overlapping a set of genes that includes: A2BP1, ABAT, CDH2, CRMP1, DMRT1, EPHA5, EPHA6, ERMP1, EVC, EVC2, FLJ35024 and VLDLR. In addition, CNVs encompassing two known frontotemporal dementia genes, CHMP2B and MAPT were found. To our knowledge, this is the first study reporting rare gene-rich CNVs in EO-FAD and early/mixed-onset AD that are likely to underlie pathogenicity in familial AD and perhaps related dementias. C1 [Hooli, B. V.; Mullin, K.; Blumenthal, M. A.; Zhang, C.; Tanzi, R. E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Kovacs-Vajna, Z. M.] Univ Brescia, Dept Informat Engn, Brescia, Italy. [Mattheisen, M.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Lange, C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Mohapatra, G.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Bertram, L.] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, D-14195 Berlin, Germany. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI Mattheisen, Manuel/B-4949-2012; Bertram, Lars/K-3889-2015 OI Mattheisen, Manuel/0000-0002-8442-493X; Bertram, Lars/0000-0002-0108-124X FU NIMH; Cure Alzheimer's Fund FX This study was funded by grants from the NIMH and the Cure Alzheimer's Fund. NR 73 TC 15 Z9 15 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUN PY 2014 VL 19 IS 6 BP 676 EP 681 DI 10.1038/mp.2013.77 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AI2BZ UT WOS:000336663100009 PM 23752245 ER PT J AU Gelernter, J Sherva, R Koesterer, R Almasy, L Zhao, H Kranzler, HR Farrer, L AF Gelernter, J. Sherva, R. Koesterer, R. Almasy, L. Zhao, H. Kranzler, H. R. Farrer, L. TI Genome-wide association study of cocaine dependence and related traits: FAM53B identified as a risk gene SO MOLECULAR PSYCHIATRY LA English DT Article DE cocaine dependence; cocaine-induced paranoia; European-American and African-American populations; GWAS; population genetics ID POPULATION-BASED SAMPLE; INDUCED PSYCHOSIS; INDUCED PARANOIA; LINKAGE SCAN; ABUSE; ALCOHOLISM; TWINS AB We report a genome-wide association study (GWAS) for cocaine dependence (CD) in three sets of African-and European-American subjects (AAs and EAs, respectively) to identify pathways, genes and alleles important in CD risk. The discovery GWAS data set (n=5697 subjects) was genotyped using the Illumina OmniQuad microarray (8 90 000 analyzed single-nucleotide polymorphisms (SNPs)). Additional genotypes were imputed based on the 1000 Genomes reference panel. Top-ranked findings were evaluated by incorporating information from publicly available GWAS data from 4063 subjects. Then, the most significant GWAS SNPs were genotyped in 2549 independent subjects. We observed one genome-wide-significant (GWS) result: rs2629540 at the FAM53B (` family with sequence similarity 53, member B') locus. This was supported in both AAs and EAs; P-value (meta-analysis of all samples) 4.28 x 10(-8). The gene maps to the same chromosomal region as the maximum peak we observed in a previous linkage study. NCOR2 (nuclear receptor corepressor 2) SNP rs150954431 was associated with P = 1.19 x 10(-9) in the EA discovery sample. SNP rs2456778, which maps to CDK1 ('cyclin-dependent kinase 1'), was associated with cocaine-induced paranoia in AAs in the discovery sample only (P-4.68 x 10(-8)). This is the first study to identify risk variants for CD using GWAS. Our results implicate novel risk loci and provide insights into potential therapeutic and prevention strategies. C1 [Gelernter, J.] Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, New Haven, CT USA. [Gelernter, J.] VA CT Healthcare Ctr, Dept Psychiat, West Haven, CT USA. [Gelernter, J.; Zhao, H.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Sherva, R.; Koesterer, R.; Farrer, L.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Almasy, L.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Zhao, H.] Yale Univ, Dept Biostat, Sch Publ Hlth, New Haven, CT USA. [Kranzler, H. R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, H. R.] Philadelphia VA Med Ctr, Dept Psychiat, Philadelphia, PA USA. [Farrer, L.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, L.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, L.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Farrer, L.] Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. RP Gelernter, J (reprint author), Yale Univ, Sch Med, Dept Psychiat, Div Human Genet, VA CT 116A2,950 Campbell Ave, West Haven, CT 06516 USA. EM joel.gelernter@yale.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU National Institutes of Health [N01-HG-65403, RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535]; VA Connecticut and Philadelphia VA MIRECCs; Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative [U01 HG004422]; Collaborative Study on the Genetics of Alcoholism (COGA) [U10 AA008401]; Collaborative Genetic Study of Nicotine Dependence (COGEND) [P01 CA089392]; Family Study of Cocaine Dependence (FSCD) [R01 DA013423]; Johns Hopkins University Center for Inherited Disease Research; 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] FX We appreciate the work in recruitment and assessment provided at McLean Hospital by Roger Weiss at the Medical University of South Carolina by Kathleen Brady and Raymond Anton and at the University of Pennsylvania by David Oslin. Genotyping services for a part of our GWAS study were provided by the Center for Inherited Disease Research (CIDR) and Yale University (Center for Genome Analysis). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (contract number N01-HG-65403). We are grateful to Ann Marie Lacobelle, Michelle Cucinelli, Christa Robinson and Greg Dalton-Kay for their excellent technical assistance, to the SSADDA interviewers, led by Yari Nunez and Michelle Slivinsky, who devoted substantial time and effort to phenotype the study sample and to John Farrell for database management assistance. This study was supported by National Institutes of Health Grants RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535 and the VA Connecticut and Philadelphia VA MIRECCs. The publicly available data sets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs0 00092.v1.p1 through dbGaP accession number phs000092.v1.p. Funding support for the Study of Addiction: Genetics and Environment (SAGE) was provided through the NIH Genes, Environment and Health Initiative (GEI; U01 HG004422). SAGE is one of the genome-wide association studies funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (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 (COGA; U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (COGEND; P01 CA089392) and the Family Study of Cocaine Dependence (FSCD; 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 (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' (HHSN268200782096C). NR 31 TC 28 Z9 28 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUN PY 2014 VL 19 IS 6 BP 717 EP 723 DI 10.1038/mp.2013.99 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA AI2BZ UT WOS:000336663100014 PM 23958962 ER PT J AU Medland, SE Jahanshad, N Neale, BM Thompson, PM AF Medland, Sarah E. Jahanshad, Neda Neale, Benjamin M. Thompson, Paul M. TI Whole-genome analyses of whole-brain data: working within an expanded search space SO NATURE NEUROSCIENCE LA English DT Review ID DE-NOVO MUTATIONS; TENSOR-BASED MORPHOMETRY; ALZHEIMERS-DISEASE; WIDE ASSOCIATION; COMMON VARIANTS; EPILEPTIC ENCEPHALOPATHIES; APOLIPOPROTEIN-E; GENE; SCHIZOPHRENIA; HERITABILITY AB Large-scale comparisons of patients and healthy controls have unearthed genetic risk factors associated with a range of neurological and psychiatric illnesses. Meanwhile, brain imaging studies are increasing in size and scope, revealing disease and genetic effects on brain structure and function, and implicating neural pathways and causal mechanisms. With the advent of global neuroimaging consortia, imaging studies are now well powered to discover genetic variants that reliably affect the brain. Genetic analyses of brain measures from tens of thousands of people are being extended to test genetic associations with signals at millions of locations in the brain, and connectome-wide, genome-wide scans can jointly screen brain circuits and genomes; these analyses and others present new statistical challenges. There is a growing need for the community to establish and enforce standards in this developing field to ensure robust findings. Here we discuss how neuroimagers and geneticists have formed alliances to discover how genetic factors affect the brain. The field is rapidly advancing with ultra-high-resolution imaging and whole-genome sequencing. We recommend a rigorous approach to neuroimaging genomics that capitalizes on its recent successes and ensures the reliability of future discoveries. C1 [Medland, Sarah E.] QIMR Berghofer Med Res Inst, Quantitat Genet, Brisbane, Qld, Australia. [Jahanshad, Neda; Thompson, Paul M.] Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Imaging Genet Ctr, Los Angeles, CA 90033 USA. [Jahanshad, Neda; Thompson, Paul M.] Univ So Calif, Dept Neurol, Los Angeles, CA 90033 USA. [Neale, Benjamin M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Neale, Benjamin M.] Massachusetts Gen Hosp, Psychiat & Neurodev Unit, Boston, MA 02114 USA. [Thompson, Paul M.] Univ So Calif, Dept Psychiat, Los Angeles, CA 90033 USA. [Thompson, Paul M.] Univ So Calif, Dept Engn, Los Angeles, CA 90033 USA. [Thompson, Paul M.] Univ So Calif, Dept Radiol, Los Angeles, CA 90033 USA. [Thompson, Paul M.] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. [Thompson, Paul M.] Univ So Calif, Dept Ophthalmol, Los Angeles, CA 90089 USA. RP Thompson, PM (reprint author), Univ So Calif, Keck Sch Med, Inst Neuroimaging & Informat, Imaging Genet Ctr, Los Angeles, CA 90033 USA. EM pthomp@usc.edu RI Medland, Sarah/C-7630-2013 OI Medland, Sarah/0000-0003-1382-380X FU Australian Research Council Future Fellowship [110100548]; US National Institutes of Health R01 [NS080655, AG040060, EB008432, MH097268, MH085667, MH089722, MH094343]; [U01 AG024904]; [P41 EB015922]; [R01 MH101244] FX S.E.M. is supported by an Australian Research Council Future Fellowship, 110100548. N.J. and P.M.T. were supported, in part, by US National Institutes of Health R01 grants NS080655, AG040060, EB008432, MH097268, MH085667, MH089722 and MH094343, and grants U01 AG024904 and P41 EB015922. B.M.N. was supported in part by R01 MH101244. NR 67 TC 37 Z9 40 U1 0 U2 21 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 JUN PY 2014 VL 17 IS 6 BP 791 EP 800 DI 10.1038/nn.3718 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AI1TO UT WOS:000336638000012 PM 24866045 ER PT J AU Pietrobon, D Moskowitz, MA AF Pietrobon, Daniela Moskowitz, Michael A. TI Chaos and commotion in the wake of cortical spreading depression and spreading depolarizations SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID RAT HIPPOCAMPAL SLICES; FAMILIAL HEMIPLEGIC MIGRAINE; CENTRAL-NERVOUS-SYSTEM; PATENT FORAMEN OVALE; CA1 PYRAMIDAL CELLS; ASPARTATE RECEPTOR ANTAGONISTS; GLUTAMATE TRANSPORTER GLT-1; CEREBRAL-BLOOD-FLOW; NEURONS IN-VITRO; ANOXIC DEPOLARIZATION AB Punctuated episodes of spreading depolarizations erupt in the brain, encumbering tissue structure and function, and raising fascinating unanswered questions concerning their initiation and propagation. Linked to migraine aura and headache, cortical spreading depression contributes to the morbidity in the world's migraine with aura population. Even more ominously, erupting spreading depolarizations accelerate tissue damage during brain injury. The once-held view that spreading depolarizations may not exist in the human brain has changed, largely because of the discovery of migraine genes that confer cortical spreading depression susceptibility, the application of sophisticated imaging tools and efforts to interrogate their impact in the acutely injured human brain. C1 [Pietrobon, Daniela] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy. [Pietrobon, Daniela] Univ Padua, CNR, Inst Neurosci, I-35121 Padua, Italy. [Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. [Moskowitz, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Moskowitz, Michael A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Pietrobon, D (reprint author), Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy. EM daniela.pietrobon@unipd.it; Moskowitz@helix.mgh.harvard.edu FU Italian Ministry of University and Research [PRIN2010]; University of Padova FX The support of the Italian Ministry of University and Research (PRIN2010) and of the University of Padova (Strategic Project 2008 and Progetto Ateneo 2012) to D.P. is gratefully acknowledged. The authors gratefully thank A. Tottene for help with the figures. NR 192 TC 57 Z9 58 U1 6 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JUN PY 2014 VL 15 IS 6 BP 379 EP 393 DI 10.1038/nrn3770 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AI3XX UT WOS:000336800100012 PM 24857965 ER PT J AU Pauls, DL Abramovitch, A Rauch, SL Geller, DA AF Pauls, David L. Abramovitch, Amitai Rauch, Scott L. Geller, Daniel A. TI Obsessive-compulsive disorder: an integrative genetic and neurobiological perspective SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID FAMILY-BASED ASSOCIATION; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; OCD COLLABORATIVE GENETICS; FACTOR-ANALYZED SYMPTOM; DIRECT INTERVIEW FAMILY; HAN CHINESE POPULATION; GLUCOSE METABOLIC-RATE; WIDE LINKAGE ANALYSIS; CEREBRAL-BLOOD-FLOW AB Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviours that are experienced as unwanted. Family and twin studies have demonstrated that OCD is a multifactorial familial condition that involves both polygenic and environmental risk factors. Neuroimaging studies have implicated the cortico-striato-thalamo-cortical circuit in the pathophysiology of the disorder, which is supported by the observation of specific neuropsychological impairments in patients with OCD, mainly in executive functions. Genetic studies indicate that genes affecting the serotonergic, dopaminergic and glutamatergic systems, and the interaction between them, play a crucial part in the functioning of this circuit. Environmental factors such as adverse perinatal events, psychological trauma and neurological trauma may modify the expression of risk genes and, hence, trigger the manifestation of obsessive-compulsive behaviours. C1 [Pauls, David L.; Abramovitch, Amitai; Rauch, Scott L.; Geller, Daniel A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Pauls, David L.; Abramovitch, Amitai; Rauch, Scott L.; Geller, Daniel A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pauls, David L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02478 USA. RP Pauls, DL (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. EM dpauls@pngu.mgh.harvard.edu; dan.geller@mgh.harvard.edu OI Abramovitch, Amitai/0000-0001-9640-0970 FU US National Institutes of Health (NIH) grants [NS16648, NS40024, MH079489] FX This work was supported in part by US National Institutes of Health (NIH) grants NS16648 (to D.L.P.), NS40024 (to D.L.P.) and MH079489 (to D.L.P.). NR 208 TC 84 Z9 85 U1 17 U2 94 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JUN PY 2014 VL 15 IS 6 BP 410 EP 424 DI 10.1038/nrn3746 PG 15 WC Neurosciences SC Neurosciences & Neurology GA AI3XX UT WOS:000336800100014 PM 24840803 ER PT J AU Kaley, T Barani, I Chamberlain, M McDermott, M Panageas, K Raizer, J Rogers, L Schiff, D Vogelbaum, M Weber, D Wen, P AF Kaley, Thomas Barani, Igor Chamberlain, Marc McDermott, Michael Panageas, Katherine Raizer, Jeffrey Rogers, Leland Schiff, David Vogelbaum, Michael Weber, Damien Wen, Patrick TI Historical benchmarks for medical therapy trials in surgery- and radiation-refractory meningioma: a RANO review SO NEURO-ONCOLOGY LA English DT Article DE anaplastic meningioma; atypical meningioma; chemotherapy meningioma; malignant meningioma; meningioma ID RECURRENT MALIGNANT GLIOMAS; BRAIN-TUMOR CONSORTIUM; PHASE-II; UNRESECTABLE MENINGIOMA; BEVACIZUMAB THERAPY; IMATINIB MESYLATE; INTERFERON-ALPHA; HYDROXYUREA; OCTREOTIDE; REGRESSION AB The outcomes of patients with surgery- and radiation-refractory meningiomas treated with medical therapies are poorly defined. Published reports are limited by small patient numbers, selection bias, inclusion of mixed histologic grades and stages of illness, and World Health Organization (WHO) criteria changes. This analysis seeks to define outcome benchmarks for future clinical trial design. A PubMed literature search was performed for all English language publications on medical therapy for meningioma. Reports were tabulated and analyzed for number of patients, histologic grade, prior therapy, overall survival, progression-free survival (PFS), and radiographic response. Forty-seven publications were identified and divided by histology and prior therapies, including only those that treated patients who were surgery and radiation refractory for further analysis. This included a variety of agents (hydroxyurea, temozolomide, irinotecan, interferon-alpha, mifepristone, octreotide analogues, megestrol acetate, bevacizumab, imatinib, erlotinib, and gefitinib) from retrospective, pilot, and phase II studies, exploratory arms of other studies, and a single phase III study. The only outcome extractable from all studies was the PFS 6-month rate, and a weighted average was calculated separately for WHO grade I meningioma and combined WHO grade II/III meningioma. For WHO I meningioma, the weighted average PFS-6 was 29% (95% confidence interval [CI]: 20.3%-37.7%). For WHO II/III meningioma, the weighted average PFS-6 was 26% (95% CI: 19.3%-32.7%). This comprehensive review confirms the poor outcomes of medical therapy for surgery- and radiation-refractory meningioma. We recommend the above PFS-6 benchmarks for future trial design. C1 [Kaley, Thomas] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA. [Barani, Igor] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Chamberlain, Marc] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [McDermott, Michael] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA. [Panageas, Katherine] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 19965 USA. [Raizer, Jeffrey] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. [Rogers, Leland] Gamma West Canc Serv, Dept Radiat Oncol, Salt Lake City, UT USA. [Schiff, David] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Vogelbaum, Michael] Cleveland Clin, Dept Neurooncol, Cleveland, OH 44106 USA. [Weber, Damien] Univ Hosp Geneva, Div Radiat Oncol, Geneva, Switzerland. [Wen, Patrick] Brigham & Womens Ctr, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA USA. RP Kaley, T (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10065 USA. EM kaleyt@mskcc.org OI Kaley, Thomas/0000-0002-2540-8518 FU BrainLab Inc; NCI ACTNOW (Accelerating Clinical Trials and Novel Oncologic Pathways Initiative); Pfizer; Novartis; Genentech FX Drs Kaley, Chamberlain, McDermott, Panageas, and Weber have no conflict of interest. Dr Barani has a BrainLab Inc research grant. Dr Raizer is on advisory boards for Novartis and Roche/Genentech and on a speakers bureau for Roche/Genentech. Dr Rogers has received an NCI ACTNOW (Accelerating Clinical Trials and Novel Oncologic Pathways Initiative) grant to study meningioma. This was applied to RTOG 0539 and used solely to increase reimbursement for enrolling institutions. Dr Schiff is on an advisory board for Genentech. Dr Vogelbaum has received honoraria from Merck. Dr Wen received research support from Pfizer, Novartis, and Genentech and is on an advisory board for Novartis and Genentech. NR 50 TC 31 Z9 31 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2014 VL 16 IS 6 BP 829 EP 840 DI 10.1093/neuonc/not330 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA AH9WO UT WOS:000336496000014 PM 24500419 ER PT J AU Augustinack, JC Magnain, C Reuter, M van der Kouwe, AJW Boas, D Fischl, B AF Augustinack, Jean C. Magnain, Caroline Reuter, Martin van der Kouwe, Andre J. W. Boas, David Fischl, Bruce TI MRI parcellation of ex vivo medial temporal lobe SO NEUROIMAGE LA English DT Review DE Entorhinal; Brodmann's area 28; Perirhinal; Brodmann's area 35; Mapping; Localization ID HUMAN CEREBRAL-CORTEX; LAMINA-SPECIFIC PATHOLOGY; HUMAN ENTORHINAL CORTEX; HUMAN PERIRHINAL CORTEX; HIGH-FIELD MRI; ALZHEIMERS-DISEASE; HUMAN-BRAIN; NEUROFIBRILLARY TANGLES; PARAHIPPOCAMPAL CORTICES; COGNITIVE IMPAIRMENT AB Recent advancements in radio frequency coils, field strength and sophisticated pulse sequences have propelled modern brain mapping and have made validation to biological standards - histology and pathology possible. The medial temporal lobe has long been established as a pivotal brain region for connectivity, function and unique structure in the human brain, and reveals disconnection in mild Alzheimer's disease. Specific brain mapping of mesbcortical areas affected with neurofibrillary tangle pathology early in disease progression provides not only an accurate description for location of these areas but also supplies spherical coordinates that allow comparison between other ex vivo cases and larger in vivo datasets. We have identified several cytoarchitectonic features in the medial temporal lobe with high resolution ex vivo MRI, including gray matter structures such as the entorhinal layer II 'islands', perirhinal layer II-III columns, presubicular 'clouds', granule cell layer of the dentate gyms as well as lamina of the hippocampus. Localization of Brodmann areas 28 and 35 (entorhinal and perirhinal, respectively) demonstrates MM based area boundaries validated with multiple methods and histological stains. Based on our findings, both myelin and Nissl staining relate to contrast in ex vivo MM. Precise brain mapping serves to create modern atlases for cortical areas, allowing accurate localization with important applications to detecting early disease processes. (C) 2013 Elsevier Inc. All rights reserved. C1 [Augustinack, Jean C.; Magnain, Caroline; Reuter, Martin; van der Kouwe, Andre J. W.; Boas, David; Fischl, Bruce] MGH, Dept Radiol, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. [Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. RP Augustinack, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM jean@nmr.mgh.harvard.edu RI Reuter, Martin/B-3456-2010 OI Reuter, Martin/0000-0002-2665-9693 FU National Center for Research Resources [P41-RR14075]; NCRR BIRN Morphometric Project [BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Institute on Aging [K01AG028521, AG022381, 5R01AG008122-22]; National Center for Alternative Medicine [RD AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963]; Shared Instrumentation Grants [1S1ORR023401, 1S10RR019307, 1S10RR023043]; Autism & Dyslexia Project - Ellison Medical Foundation; NIH Blueprint for Neuroscience Research [5U01-MH093765]; multi-institutional Human Connectome Project FX The authors would like to thank Kristen Huber and Sita Kakunoori for technical support. Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758), the National Institute on Aging (K01AG028521, AG022381, 5R01AG008122-22), the National Center for Alternative Medicine (RD AT005728-01), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963), and was made possible by the resources provided by Shared Instrumentation Grants 1S1ORR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation, and by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. NR 71 TC 12 Z9 12 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2014 VL 93 SI SI BP 252 EP 259 DI 10.1016/j.neuroimage.2013.05.053 PN 2 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AI0RG UT WOS:000336556500011 PM 23702414 ER PT J AU Bludau, S Eickhoff, SB Mohlberg, H Caspers, S Laird, AR Fox, PT Schleicher, A Zilles, K Amunts, K AF Bludau, S. Eickhoff, S. B. Mohlberg, H. Caspers, S. Laird, A. R. Fox, P. T. Schleicher, A. Zilles, K. Amunts, K. TI Cytoarchitecture, probability maps and functions of the human frontal pole SO NEUROIMAGE LA English DT Article ID ROSTRAL PREFRONTAL CORTEX; HUMAN ORBITOFRONTAL CORTEX; HUMAN CEREBRAL-CORTEX; PRIMARY SOMATOSENSORY CORTEX; INTERINDIVIDUAL VARIABILITY; STEREOTAXIC SPACE; MICROSTRUCTURAL PARCELLATION; INTERSUBJECT VARIABILITY; QUANTITATIVE APPROACH; PROSPECTIVE MEMORY AB The frontal pole has more expanded than any other part in the human brain as compared to our ancestors. It plays an important role for specifically human behavior and cognitive abilities, e.g. action selection (Kovach et al., 2012). Evidence about divergent functions of its medial and lateral part has been provided, both in the healthy brain and in psychiatric disorders. The anatomical correlates of such functional segregation, however, are still unknown due to a lack of stereotaxic, microstructural maps obtained in a representative sample of brains. Here we show that the human frontopolar cortex consists of two cytoarchitectonically and functionally distinct areas: lateral frontopolar area 1 (Fp1) and medial frontopolar area 2 (Fp2). Based on observer-independent mapping in serial, cell-body stained sections of 10 brains, three-dimensional, probabilistic maps of areas Fp1 and Fp2 were created. They show, for each position of the reference space, the probability with which each area was found in a particular voxel. Applying these maps as seed regions for a meta-analysis revealed that Fp1 and Fp2 differentially contribute to functional networks: Fp1 was involved in cognition, working memory and perception, whereas Fp2 was part of brain networks underlying affective processing and social cognition. The present study thus disclosed cortical correlates of a functional segregation of the human frontopolar cortex. The probabilistic maps provide a sound anatomical basis for interpreting neuroimaging data in the living human brain, and open new perspectives for analyzing structure-function relationships in the prefrontal cortex. The new data will also serve as a starting point for further comparative studies between human and non-human primate brains. This allows finding similarities and differences in the organizational principles of the frontal lobe during evolution as neurobiological basis for our behavior and cognitive abilities. (C) 2013 Elsevier Inc. All rights reserved. C1 [Bludau, S.; Eickhoff, S. B.; Mohlberg, H.; Caspers, S.; Schleicher, A.; Zilles, K.; Amunts, K.] Res Ctr Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany. [Eickhoff, S. B.] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, D-40001 Dusseldorf, Germany. [Laird, A. R.; Fox, P. T.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Laird, A. R.; Fox, P. T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Fox, P. T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Zilles, K.] RVVTH Univ Aachen, Dept Psychiat Psychotherapy & Psychosomat, D-52074 Aachen, Germany. [Zilles, K.; Amunts, K.] JARA, Juelich Aachen Res Alliance, Julich, Germany. [Amunts, K.] Univ Dusseldorf, C&O Vogt Inst Brain Res, D-40001 Dusseldorf, Germany. [Laird, A. R.] Florida Int Univ, Dept Phys, Miami, FL 33199 USA. RP Bludau, S (reprint author), Res Ctr Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany. EM s.bludau@fz-juelich.de RI Amunts, Katrin/I-3470-2013; Zilles, Karl/J-9704-2013; Fox, Peter/B-4725-2010; Caspers, Svenja/H-9346-2013; Eickhoff, Simon/K-2061-2013; OI Amunts, Katrin/0000-0001-5828-0867; Zilles, Karl/0000-0002-4705-4175; Zilles, Karl/0000-0001-9296-9959; Fox, Peter/0000-0002-0465-2028; Caspers, Svenja/0000-0001-5083-4669; Eickhoff, Simon/0000-0001-6363-2759; Bludau, Sebastian/0000-0001-6173-9050 FU BMBF [01GW0612]; Helmholtz Alliance for Mental Health in an Aging Society (HeIMA); Helmholtz Alliance on Systems Biology (Human Brain Model) FX This study was supported by the BMBF (01GW0612, K.A.). Further funding was granted by the Helmholtz Alliance for Mental Health in an Aging Society (HeIMA; KA., K.Z.) and by the Helmholtz Alliance on Systems Biology (Human Brain Model; K.Z., S.B.E.). The authors thank Katerina Semendeferi for critical review of the manuscript and for helpful discussions. NR 104 TC 43 Z9 43 U1 5 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2014 VL 93 SI SI BP 260 EP 275 DI 10.1016/j.neuroimage.2013.05.052 PN 2 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AI0RG UT WOS:000336556500012 PM 23702412 ER PT J AU Buckner, RL Yeo, BTT AF Buckner, Randy L. Yeo, B. T. Thomas TI Borders, map clusters, and supra-areal organization in visual cortex SO NEUROIMAGE LA English DT Review DE Boundary mapping; Functional connectivity; Resting-state connectivity; fMRI; Brodmann Area; Visual cortex ID PRIMATE CEREBRAL-CORTEX; FUNCTIONAL CONNECTIVITY; HUMAN BRAIN; FIELD; ARCHITECTURE; TOPOGRAPHY; REPRESENTATION; EVOLUTION; NETWORKS; STRIATE AB V1 is a canonical cortical area with clearly delineated architectonic boundaries and a continuous topographic representation of the visual hemifield. It thus serves as a touchstone for understanding what new mapping methods can tell us about cortical organization. By parcellating human cortex using local gradients in functional connectivity, Wig et al. (2014-in this issue) detected the V1 border with V2. By contrast, previously-published clustering methods that focus on global similarity in connectivity reveal a supra-areal organization that emphasizes eccentricity bands spanning V1 and its neighboring extrastriate areas; i.e. in the latter analysis, the V1 border is not evident. Thus the focus on local connectivity gradients emphasizes qualitatively different features of cortical organization than are captured by global similarity measures. What is intriguing to consider is that each kind of information might be telling us something unique about cortical organization. Global similarity measures may be detecting map clusters and other supra-areal arrangements that reflect a fundamental level of organization. (C) 2013 Elsevier Inc. All rights reserved. C1 [Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Yeo, B. T. Thomas] Natl Univ Singapore, Dept Elect & Comp Engn, Singapore 117548, Singapore. RP Buckner, RL (reprint author), Harvard Univ, 52 Oxford St,Northwest Bldg,280-06, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu OI Yeo, B.T. Thomas/0000-0002-0119-3276 FU National University of Singapore Tier 1 Grant [R-263-000-A91-750]; Center for Functional Neuroimaging Technologies [P41EB015896]; Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital [S10RR021110, S10RR023401, S10RR019307] FX We thank Roger Tootell for his thoughtful comments on an earlier draft, and Marcello Rosa and Mark Schira for the figures. We also thank the support of the National University of Singapore Tier 1 Grant (R-263-000-A91-750). Data were provided by the Brain Genomics Superstruct Project (Principal Investigators: Randy Buckner, Jordan Smoller, and Joshua Roffman). This research utilized resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896 and instruments supported by S10RR021110, S10RR023401 and S10RR019307 from the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital. NR 35 TC 11 Z9 11 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2014 VL 93 SI SI BP 292 EP 297 DI 10.1016/j.neuroimage.2013.12.036 PN 2 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AI0RG UT WOS:000336556500014 PM 24374078 ER PT J AU Hoeppner, BB Bidwell, LC Colby, SM Barnett, NP AF Hoeppner, Bettina B. Bidwell, L. Cinnamon Colby, Suzanne M. Barnett, Nancy P. TI Smoking Patterns and Their Relationship to Drinking Among First-Year College Students SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID CIGARETTE-SMOKING; INTERMITTENT SMOKING; NONDAILY SMOKING; NATURAL-HISTORY; DAILY SMOKERS; YOUNG-ADULTS; ALCOHOL-USE; LIGHT; UNIVERSITIES; TRAJECTORIES AB Unlike older smokers, young adult smokers frequently engage in light and intermittent smoking. It remains unclear how stable such smoking patterns are over time, as substantial variability exists between these smokers. This study identified subgroups of college student smokers based on the trajectory of their smoking frequency during the first year of college, thereby examining stability versus instability over time. We then tested if the interplay between drinking and smoking differed in the identified groups to determine the relative role drinking may play in intermittent versus more regular smoking. Incoming college students at 3 institutions completed online biweekly surveys of their daily substance use throughout the first year of college. Students who reported smoking at least 1 cigarette during this year (n = 266) were included in analyses (70% female, 74% White). Group-based trajectory modeling identified 5 groups of smokers, 3 of which maintained their smoking frequency throughout the year (77%), and 2 groups of infrequent smokers showed significant trends (11% increasing, 12% decreasing). Notably, nondaily smoking was maintained at different specific frequencies (e.g., 1 vs. 3 days per week). Identified groups differed in the relationship between drinking and smoking, where cooccurrence was particularly strong among infrequent smokers, and trends in smoking quantity differed between groups. While there was a diversity of smoking patterns in the sample, patterns of intermittent smoking remain relatively stable for a majority of students throughout the year. Intervention messages targeting drinking and smoking should be tailored on the basis of smoking frequency. C1 [Hoeppner, Bettina B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Addict Med, Boston, MA USA. [Bidwell, L. Cinnamon; Colby, Suzanne M.; Barnett, Nancy P.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. RP Hoeppner, BB (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM bhoeppner@partners.org FU National Institute on Alcohol Abuse and Alcoholism [R01AA013970]; National Institute on Drug Abuse [K01DA027097, K23DA033302] FX This study was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (R01AA013970) and the National Institute on Drug Abuse (K01DA027097, K23DA033302). NR 38 TC 0 Z9 0 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 EI 1469-994X J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JUN PY 2014 VL 16 IS 6 BP 743 EP 752 DI 10.1093/ntr/ntt205 PG 10 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA AH9UX UT WOS:000336491000014 PM 24415586 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI Approval After Phase I: Ceritinib Runs the Three-Minute Mile SO ONCOLOGIST LA English DT Editorial Material ID CANCER C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Chabner, BA (reprint author), 10 North Grove St,LRH 214, Boston, MA 02114 USA. EM bchabner@partners.org FU NCI NIH HHS [K12 CA087723] NR 4 TC 14 Z9 14 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JUN PY 2014 VL 19 IS 6 BP 577 EP 578 DI 10.1634/theoncologist.2014-0143 PG 2 WC Oncology SC Oncology GA AI2WF UT WOS:000336718500001 PM 24789171 ER PT J AU Fathi, AT Sadrzadeh, H Comander, AH Higgins, AJ Bardia, A Perry, A Burke, A Silver, R Matulis, CR Straley, KS Yen, KE Agresta, S Kim, H Schenkein, DP Borger, DR AF Fathi, Amir T. Sadrzadeh, Hossein Comander, Amy H. Higgins, Amichaela J. Bardia, Aditya Perry, Ashley Burke, Ameghan Silver, Regina Matulis, Christina R. Straley, Kimberly S. Yen, Katharine E. Agresta, Sam Kim, Hyeryun Schenkein, David P. Borger, Darrell R. TI Isocitrate Dehydrogenase 1 (IDH1) Mutation in Breast Adenocarcinoma Is Associated With Elevated Levels of Serum and Urine 2-Hydroxyglutarate SO ONCOLOGIST LA English DT Article DE Isocitrate dehydrogenase 1; 2-Hydroxyglutarate; Breast adenocarcinoma; Targeted therapy ID ACUTE MYELOID-LEUKEMIA; DIFFERENTIATION; FREQUENT; INHIBITION; PROGNOSIS; NEOPLASMS; CANCERS; GLIOMAS; TUMORS; CELLS AB Mutations in the IDH1 and IDH2 (isocitrate dehydrogenase) genes have been discovered across a range of solid-organ and hematologic malignancies, including acute myeloid leukemia, glioma, chondrosarcoma, and cholangiocarcinoma. An intriguing aspect of IDH-mutant tumors is the aberrant production and accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which may play a pivotal oncogenic role in these malignancies. Wedescribe the first reported case of an IDH1 p.R132L mutation in a patient with hormone receptor-positive (HR+) breast adenocarcinoma. This patient was initially treated for locally advanced disease, but then suffered a relapse and metastasis, at which pointan IDH1-R132 mutation was discovered in an affected lymph node. The mutation was subsequently found in the primary tumor tissue and all metastatic sites, but not in an uninvolved lymph node. In addition, the patient's serum and urine displayed marked elevations in the concentration of 2-HG, significantly higher than that measured in six other patients with metastatic HR+ breast carcinoma whose tumors were found to harbor wild-type IDH1. In summary, IDH1 mutations may impact a rare subgroup of patients with breast adenocarcinoma. This may suggest future avenues for disease monitoring through noninvasive measurement of 2-HG, as well as for the development and study of targeted therapies against the aberrant IDH1 enzyme. C1 [Fathi, Amir T.; Sadrzadeh, Hossein; Comander, Amy H.; Higgins, Amichaela J.; Bardia, Aditya; Perry, Ashley; Burke, Ameghan; Silver, Regina; Matulis, Christina R.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Straley, Kimberly S.; Yen, Katharine E.; Agresta, Sam; Kim, Hyeryun; Schenkein, David P.; Borger, Darrell R.] Agios Pharmaceut, Cambridge, MA USA. RP Fathi, AT (reprint author), Massachusetts Gen Hosp, Zero Emerson Pl,Suite 118, Boston, MA 02114 USA. EM afathi@partners.org FU Massachusetts General Hospital Cancer Center Thematic Priority [3] FX This work was supported in part by a Massachusetts General Hospital Cancer Center Thematic Priority #3 Grant. Amir T. Fathi, Hossein Sadrzadeh, and Darrell R. Borger contributed equally to this article. NR 42 TC 12 Z9 12 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JUN PY 2014 VL 19 IS 6 BP 602 EP 607 DI 10.1634/theoncologist.2013-0417 PG 6 WC Oncology SC Oncology GA AI2WF UT WOS:000336718500005 PM 24760710 ER PT J AU Wolpin, BM Rubinson, DA Wang, XX Chan, JA Cleary, JM Enzinger, PC Fuchs, CS McCleary, NJ Meyerhardt, JA Ng, K Schrag, D Sikora, AL Spicer, BA Killion, L Mamon, H Kimmelman, AC AF Wolpin, Brian M. Rubinson, Douglas A. Wang, Xiaoxu Chan, Jennifer A. Cleary, James M. Enzinger, Peter C. Fuchs, Charles S. McCleary, Nadine J. Meyerhardt, Jeffrey A. Ng, Kimmie Schrag, Deborah Sikora, Allison L. Spicer, Beverly A. Killion, Leah Mamon, Harvey Kimmelman, Alec C. TI Phase II and Pharmacodynamic Study of Autophagy Inhibition Using Hydroxychloroquine in Patients With Metastatic Pancreatic Adenocarcinoma SO ONCOLOGIST LA English DT Article AB Background. Autophagy is a catabolic pathway that permits cells to recycle intracellular macromolecules, and its inhibition reduces pancreatic cancer growth in model systems. We evaluated hydoxychloroquine (HCQ), an inhibitor of autophagy, in patients with pancreatic cancer and analyzed pharmacodynamic markers in treated patients and mice. Methods. Patients with previously treated metastatic pancreatic cancer were administered HCQ at 400 mg (n = 10) or 600 mg (n = 10) twice daily. The primary endpoint was 2-month progression-free survival (PFS). We analyzed peripheral lymphocytes from treated mice to identify pharmacodynamic markers of autophagy inhibition that were then assessed in peripheral lymphocytes from patients. Results. Among 20 patients enrolled, 2 (10%) were without progressive disease at 2 months. Median PFS and overall survival were 46.5 and 69.0 days, respectively. Treatment-related grade 3/4 adverse events were lymphopenia (n = 1) and elevated alanine aminotransferase (n = 1). Tolerability and efficacy were similar at the two dose levels. Analysis of treated murine lymphocytes suggested that LC3-II expression by Western blot is a reliable marker for autophagy inhibition. Analysis of LC3-II in patient lymphocytes demonstrated inconsistent autophagy inhibition. Conclusion. Mouse studies identified LC3-II levels in peripheral lymphocytes as a potential pharmacodynamic marker of autophagy inhibition. In patients with previously treated metastatic pancreatic cancer, HCQ monotherapy achieved inconsistent autophagy inhibition and demonstrated negligible therapeutic efficacy. C1 [Wolpin, Brian M.; Rubinson, Douglas A.; Wang, Xiaoxu; Chan, Jennifer A.; Cleary, James M.; Enzinger, Peter C.; Fuchs, Charles S.; McCleary, Nadine J.; Meyerhardt, Jeffrey A.; Ng, Kimmie; Schrag, Deborah; Sikora, Allison L.; Spicer, Beverly A.; Killion, Leah; Mamon, Harvey; Kimmelman, Alec C.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Wolpin, Brian M.; Rubinson, Douglas A.; Wang, Xiaoxu; Chan, Jennifer A.; Cleary, James M.; Enzinger, Peter C.; Fuchs, Charles S.; McCleary, Nadine J.; Meyerhardt, Jeffrey A.; Ng, Kimmie; Schrag, Deborah; Sikora, Allison L.; Spicer, Beverly A.; Killion, Leah; Mamon, Harvey; Kimmelman, Alec C.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kimmelman, AC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM bwolpin@partners.org; akimmelman@partners.org FU NIH from the National Cancer Institute [K07 CA140790, 1R01CA157490, 1R01CA124908, P50127003]; American Society of Clinical Oncology Career Development Award; Howard Hughes Medical Institute Early Career Physician-Scientist Award; Lustgarten Foundation; Promises for Purple; American Cancer Society [RSG-13-298-01-TBG]; Department of Defense Discovery Award [W81XWH-12-1-0459]; Lustgarten Foundation for Pancreatic Cancer Research; Robert T. and Judith B. Hale Fund for Pancreatic Cancer Research FX Brian M. Wolpin is supported by NIH Grant K07 CA140790 from the National Cancer Institute, an American Society of Clinical Oncology Career Development Award, a Howard Hughes Medical Institute Early Career Physician-Scientist Award, the Lustgarten Foundation, and Promises for Purple. Alec C. Kimmelman is supported by NIH Grant 1R01CA157490 from the National Cancer Institute, American Cancer Society Grant RSG-13-298-01-TBG, a Department of Defense Discovery Award (W81XWH-12-1-0459), and the Lustgarten Foundation for Pancreatic Cancer Research. Charles S. Fuchs is supported by NIH Grant 1R01CA124908 and P50127003 from the National Cancer Institute and the Robert T. and Judith B. Hale Fund for Pancreatic Cancer Research. NR 0 TC 43 Z9 44 U1 0 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JUN PY 2014 VL 19 IS 6 BP 637 EP 638 DI 10.1634/theoncologist.2014-0086 PG 2 WC Oncology SC Oncology GA AI2WF UT WOS:000336718500010 PM 24821822 ER PT J AU Khera, N Emmert, A Storer, BE Sandmaier, BM Alyea, EP Lee, SJ AF Khera, Nandita Emmert, Amy Storer, Barry E. Sandmaier, Brenda M. Alyea, Edwin P. Lee, Stephanie J. TI Costs of Allogeneic Hematopoietic Cell Transplantation Using Reduced Intensity Conditioning Regimens SO ONCOLOGIST LA English DT Article DE Economics; Hematopoietic stem cell transplantation; Costs; Allogeneic transplantation ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; HIGH-DOSE REGIMENS; HEMATOLOGIC MALIGNANCIES; OLDER PATIENTS; COMPLICATIONS; PREVENTION; RECIPIENTS; OUTCOMES; DONOR AB Reduced intensity conditioning (RIC) regimens have allowed older patients and those with comorbidities to receive hematopoietic cell transplantation (HCT). We analyzed medical costs from the beginning of conditioning to 100 days after HCT for 484 patients and up to 2 years for 311 patients who underwent a RIC HCT at two institutions from January 2008 to December 2010. Multiple linear regression was used to analyze the association between clinical variables, center effect, and costs. Patient and transplant characteristics were comparable between the sites, although differences were seen in pretransplant performance scores. Significant predictors for lower costs for the first 100 days included a diagnosis of lymphoma/myeloma and use of human leukocyte antigen-matched related donors. Grade II-IV acute graft-versus-host disease (GVHD) was associated with higher costs. The overall short-term costs between the two institutions were comparable when adjusted for clinical variables (p = .43). Late costs between 100 days and 2 years after HCT were available for one cohort (n = 311); median costs during this period were $39,000 and accounted for 39% of costs during the first 2 years. Late costs were not associated with any pretransplant variables, but were higher with extensive chronic GVHD and death. After adjustment for clinical characteristics, the overall costs of the RIC transplants were similar between the two institutions despite different management approaches (inpatient vs. outpatient conditioning) and accounting methodologies. Use of unrelated/alternative donors, transplant for diseases other than lymphoma or myeloma, and acute GVHD were predictors for higher early costs, and extensive chronic GVHD and death were associated with higher late costs. C1 [Khera, Nandita] Mayo Clin Arizona, Div Hematol Oncol, Phoenix, AZ USA. [Emmert, Amy; Alyea, Edwin P.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Storer, Barry E.; Sandmaier, Brenda M.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Khera, N (reprint author), 5777 East Mayo Blvd,C-211, Phoenix, AZ 85054 USA. EM Khera.Nandita@mayo.edu FU NIH [CA18029, HL36444, CA78902] FX This work was supported by NIH Grants CA18029, HL36444, and CA78902. NR 23 TC 7 Z9 7 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JUN PY 2014 VL 19 IS 6 BP 639 EP 644 DI 10.1634/theoncologist.2013-0406 PG 6 WC Oncology SC Oncology GA AI2WF UT WOS:000336718500011 PM 24797822 ER PT J AU Grothey, A George, S van Cutsem, E Blay, JY Sobrero, A Demetri, GD AF Grothey, Axel George, Suzanne van Cutsem, Eric Blay, Jean-Yves Sobrero, Alberto Demetri, George D. TI Optimizing Treatment Outcomes With Regorafenib: Personalized Dosing and Other Strategies to Support Patient Care SO ONCOLOGIST LA English DT Article DE Regorafenib; Adverse events; Dose optimization; Supportive management; Hand-foot skin reaction; Multikinase inhibitor ID FOOT SKIN REACTION; MULTIKINASE INHIBITOR REGORAFENIB; GASTROINTESTINAL STROMAL TUMORS; ADVANCED SOLID TUMORS; RENAL-CELL CARCINOMA; BAY 73-4506; PHASE-I; COLORECTAL-CANCER; JAPANESE PATIENTS; SUNITINIB AB Regorafenib is an oral multikinase inhibitor that inhibits several kinases relevant to tumor biology in several cancers, including colorectal carcinoma (CRC) and gastrointestinal stromal tumor (GIST). In phase III trials, regorafenib significantly improved overall survival versus placebo in patients with metastatic CRC progressing after all available standard therapies, and significantly prolonged progression-free survival in patients with advanced GIST in whom at least imatinib and sunitinib had failed. Thus, this agent holds promise as a new standard of care for CRC and GIST patients after disease progression following all other approved therapies. The clinical trials reported to date show that this new treatment has a consistent adverse event profile that is quite different from that of traditional cytotoxic chemotherapies. The most common adverse events of regorafenib include dermatologic and mucosal toxicities (especially hand-foot skin reaction, rash, and oral mucositis), constitutional symptoms (e.g., fatigue, nausea, and weight loss), vascular effects (especially hypertension), and gastrointestinal symptoms (e.g., diarrhea). To help health care professionals anticipate and manage the adverse events associated with regorafenib, we describe our experiences in clinical trials and show that such toxicities can be effectively managed with close observation of patients from initiation of dosing, along with prompt appropriate interventions, including dose modifications, if necessary. C1 [Grothey, Axel] Mayo Clin, Rochester, MN 55905 USA. [George, Suzanne; Demetri, George D.] Dana Farber Canc Inst, Boston, MA 02215 USA. [George, Suzanne; Demetri, George D.] Harvard Univ, Sch Med, Boston, MA USA. [van Cutsem, Eric] Univ Hosp Gasthuisberg Leuven, Louvain, Belgium. [Blay, Jean-Yves] Ctr Leon Berard, F-69373 Lyon, France. [Blay, Jean-Yves] Univ Lyon 1, F-69365 Lyon, France. [Sobrero, Alberto] IRCCS San Martino, Genoa, Italy. RP Grothey, A (reprint author), Mayo Clin, Div Med Oncol, 200 First St SW, Rochester, MN 55905 USA. EM grothey.axel@mayo.edu; suzanne_george@dfci.harvard.edu RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X FU Bayer HealthCare Pharmaceuticals FX The academic authors take full responsibility for the content of this review. Sara Black, of Succinct Healthcare Communication, provided editorial assistance, which was funded by Bayer HealthCare Pharmaceuticals. BayerHealthCare Pharmaceuticals was allowed to review the manuscript for factual correctness, but did not influence the content or decision to publish. Axel Grothey and Suzanne George contributed equally to this article. NR 31 TC 16 Z9 16 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JUN PY 2014 VL 19 IS 6 BP 669 EP 680 DI 10.1634/theoncologist.2013-0059 PG 12 WC Oncology SC Oncology GA AI2WF UT WOS:000336718500015 PM 24821824 ER PT J AU Skaperdas, E Tuepker, A Nicolaidis, C Robb, JK Kansagara, D Hickam, DH AF Skaperdas, Eleni Tuepker, Anais Nicolaidis, Christina Robb, Jessica K. Kansagara, Devan Hickam, David H. TI Congestive heart failure self-management among US veterans: The role of personal and professional advocates SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Primary care redesign; Self-management; Qualitative research; Heart failure; Veterans; US ID CONTROLLED-TRIAL; CARE MANAGEMENT; EXPERIENCES; ADHERENCE; PATIENT; PROGRAM; RISK AB Objective: Understand patients' experiences with primary care services for congestive heart failure (CHF) and explore the relationship between health services and self-management. Methods: We conducted semi-structured interviews with thirty-nine patients with CHF receiving care at one Veterans Affairs Medical Center (VA). We analyzed data using thematic content analysis. Results: Participants acknowledged the importance of ongoing engagement in the plan of care for CHF. They attributed success in this effort to be greatly influenced by personal advocates. The advocates included both members of the healthcare team with whom they had a continuity relationship and friends or family members who assisted on a daily basis. Participants also identified psychological symptoms as a major barrier to carrying out self-care. Conclusion: Patients identify relationships with health care workers, help from family and friends, and mental health problems as major influences on the ability to manage their CHF. Practice implications: Efforts to optimize CHF self-management should attend to health system and psychosocial barriers to care. Published by Elsevier Ireland Ltd. C1 [Skaperdas, Eleni; Tuepker, Anais; Robb, Jessica K.; Kansagara, Devan; Hickam, David H.] Vet Hlth Adm, Portland VA Med Ctr Hlth Serv Res & Dev, VISN PACT Demonstrat Lab 20, Portland, OR USA. [Tuepker, Anais; Kansagara, Devan] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Nicolaidis, Christina] Portland State Univ, Sch Social Work, Portland, OR 97207 USA. [Nicolaidis, Christina] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Hickam, David H.] Patient Centered Outcomes Res Inst, Washington, DC USA. RP Skaperdas, E (reprint author), Portland VA Med Ctr, Mailcode R&D63,POB 1034, Portland, OR 97207 USA. EM eleni.skaperdas@va.gov FU VA Office of Patient Care FX We thank the Veterans, their family members, and close friends for sharing their experiences, and gratefully acknowledge the contribution of all members of the VISN 20 PACT Demonstration Lab. Funding for the PACT Demonstration Laboratory initiative is provided by the VA Office of Patient Care. NR 28 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JUN PY 2014 VL 95 IS 3 BP 371 EP 377 DI 10.1016/j.pec.2014.03.002 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AI3QD UT WOS:000336776100011 PM 24666772 ER PT J AU Koenig, CJ Maguen, S Monroy, JD Mayott, L Seal, KH AF Koenig, Christopher J. Maguen, Shira Monroy, Jose D. Mayott, Lindsay Seal, Karen H. TI Facilitating culture-centered communication between health care providers and veterans transitioning from military deployment to civilian life SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Patient-centered care; Health communication; Culture; Post-deployment health; Readjustment experience; Military veterans; USA ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; AFGHANISTAN VETERANS; MENTAL-HEALTH; DISCOURSE ANALYSIS; COMBAT VETERANS; IRAQ; HOME; BARRIERS; FAMILY AB Objective: To describe returning veterans' transition experience from military to civilian life and to educate health care providers about culture-centered communication that promotes readjustment to civilian life. Methods: Qualitative, in-depth, semi-structured interviews with 17 male and 14 female Iraq and Afghanistan veterans were audio recorded, transcribed verbatim, and analyzed using Grounded Practical Theory. Results: Veterans described disorientation when returning to civilian life after deployment. Veterans' experiences resulted from an underlying tension between military and civilian identities consistent with reverse culture shock. Participants described challenges and strategies for managing readjustment stress across three domains: intrapersonal, professional/educational, and interpersonal. Conclusions: To provide patient-centered care to returning Iraq and Afghanistan veterans, health care providers must be attuned to medical, psychological, and social challenges of the readjustment experience, including reverse culture shock. Cultufe-centered communication may help veterans integrate positive aspects of military and civilian identities, which may promote full reintegration into civilian life. Practice implications: Health care providers may promote culture-centered interactions by asking veterans to reflect about their readjustment experiences. By actively eliciting challenges and helping veterans' to identify possible solutions, health care providers may help veterans integrate military and civilian identities through an increased therapeutic alliance and social support throughout the readjustment process. Published by Elsevier Ireland Ltd. C1 [Koenig, Christopher J.; Maguen, Shira; Monroy, Jose D.; Mayott, Lindsay; Seal, Karen H.] San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. [Koenig, Christopher J.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Maguen, Shira; Seal, Karen H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Koenig, Christopher J.; Mayott, Lindsay; Seal, Karen H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Monroy, Jose D.] San Francisco State Univ, Dept Psychol, San Francisco, CA 94132 USA. RP Koenig, CJ (reprint author), San Francisco Vet Adm Med Ctr, Dept Med, 4150 Clement St,111-A1, San Francisco, CA 94121 USA. EM Christopher.Koenig@va.gov OI Koenig, Christopher J./0000-0003-0884-4120 FU Department of Defense [W81XWH-08-2-0106] FX Department of Defense award W81XWH-08-2-0106 funded this study. The funders had no role in the design, data analysis, writing or approval of the manuscript. NR 66 TC 5 Z9 5 U1 8 U2 31 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 JUN PY 2014 VL 95 IS 3 BP 414 EP 420 DI 10.1016/j.pec.2014.03.016 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA AI3QD UT WOS:000336776100017 PM 24742536 ER PT J AU McCracken, JT Badashova, KK Posey, DJ Aman, MG Scahill, L Tierney, E Arnold, LE Vitiello, B Whelan, F Chuang, SZ Davies, M Shah, B McDougle, CJ Nurmi, EL AF McCracken, J. T. Badashova, K. K. Posey, D. J. Aman, M. G. Scahill, L. Tierney, E. Arnold, L. E. Vitiello, B. Whelan, F. Chuang, S. Z. Davies, M. Shah, B. McDougle, C. J. Nurmi, E. L. TI Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders SO PHARMACOGENOMICS JOURNAL LA English DT Article DE autism spectrum disorders; dopamine; genetics; hyperactivity; methylphenidate ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; DOPAMINE TRANSPORTER GENOTYPE; ABERRANT BEHAVIOR CHECKLIST; ADHD CHILDREN; DOSE-RESPONSE; RECEPTOR GENE; SCHIZOPHRENIC CHILDREN; GENOME BROWSER; ASSOCIATION AB Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P< 0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability. C1 [McCracken, J. T.; Badashova, K. K.; Whelan, F.; Shah, B.; Nurmi, E. L.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci, Los Angeles, CA 90024 USA. [Posey, D. J.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Aman, M. G.; Arnold, L. E.] Ohio State Univ, Nisonger Ctr UCEDD, Dept Psychiat, Columbus, OH 43210 USA. [Aman, M. G.; Arnold, L. E.] Ohio State Univ, Nisonger Ctr UCEDD, Dept Psychol, Columbus, OH 43210 USA. [Scahill, L.] Yale Univ, Child Study Ctr, New Haven, CT USA. [Tierney, E.] Johns Hopkins Univ, Kennedy Krieger Inst, Dept Psychiat, Baltimore, MD USA. [Vitiello, B.] NIMH, NIH, Bethesda, MD 20892 USA. [Chuang, S. Z.; Davies, M.] Columbia Univ, Dept Psychiat, New York, NY USA. [McDougle, C. J.] Massachusetts Gen Hosp, Lurie Autism Ctr, Dept Psychiat, Boston, MA 02114 USA. RP McCracken, JT (reprint author), UCLA NPI Semel Inst, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM jmccracken@mednet.ucla.edu RI Nurmi, Erika/P-4627-2014; OI Nurmi, Erika/0000-0003-4893-8957; Scahill, Lawrence/0000-0001-5073-1707 FU NIMH [N01 MH-70070, N01 MH-70009, N01 MH-70001, N01 MH 80011, MH-01805, MH094613, T32MH073517, MH-68627]; NIH Division of Research Resources General Clinical Research Center [M01 RR-00750, M01 RR-00052, M01 RR-00034, M01 RR-06022]; Korczak Foundation FX The RUPP Autism Network comprises the following investigators listed by role and study site: Ohio State University: principal investigator Michael G Amen, PhD, co-investigators L Eugene Arnold, MEd, MD, Yaser Ramadan, MD, Andrea Witwer, MA, Ronald Lindsay, MD and Patricia Nash, MD; University of California at Los Angeles: principal investigator James T McCracken, MD, co-investigators Bhavik Shah, MD, James Mc Gough, MD, Pegeen Cronin, PhD, Lisa Lee, BA; Indiana University: principal investigator Christopher J McDougle, MD, co-investigators David Posey, MD, Naomi Swiezy, PhD, Arlene Kohn, BA; Yale University: principal investigator Lawrence Scahill, MSN, PhD, co-investigators Andres Martin, MD, Kathleen Koenig, MSN, Fred Volkmar, MD, Deirdre Carroll, MSN, Allison Lancor, BS; Kennedy Krieger Institute: principal investigator Elaine Tierney, MD, co-investigators Jaswinder Ghuman, MD, Nilda Gonzalez, MD, Marco Grados, MD; National Institute of Mental Health: principal investigator Benedetto Vitiello, MD, co-investigator Louise Ritz, MBA; statisticians: Shirley Z Chuang, MS, Mark Davies, MPH, of Columbia University; data management: James Robinson, MEd, Don McMahon, MS, Nathan Kline Institute. Research supported by NIMH contracts N01 MH-70070 (principal investigator: Dr McCracken), N01 MH-70009 (principal investigator: Dr Scahill), N01 MH-70001 (principal investigator: Dr McDougle), and N01 MH 80011 (principal investigator: Dr Amen); by NIH Division of Research Resources General Clinical Research Center grants M01 RR-00750 (to Indiana University), M01 RR-00052 (to John Hopkins University), M01 RR-00034 (to Ohio University) and M01 RR-06022 (to Yale University); by NIMH grants MH-01805 (to Dr McCracken) NIMH grants MH094613 and T32MH073517 (Dr Nurmi) and MH-68627 (to Dr Posey); and by funding from the Korczak Foundation (to Dr Scahill). The opinions and assertions contained in this report are the private views of the authors and are not to be construed as official or as reflecting the views of the National Institute of Mental Health, the National Institutes of Health, or the Department of Health and Human Services. NR 67 TC 11 Z9 12 U1 3 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD JUN PY 2014 VL 14 IS 3 BP 295 EP 302 DI 10.1038/tpj.2013.23 PG 8 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA AI0SK UT WOS:000336560000014 PM 23856854 ER PT J AU Clarke, TK Crist, RC Ang, A Ambrose-Lanci, LM Lohoff, FW Saxon, AJ Ling, W Hillhouse, MP Bruce, RD Woody, G Berrettini, WH AF Clarke, T-K Crist, R. C. Ang, A. Ambrose-Lanci, L. M. Lohoff, F. W. Saxon, A. J. Ling, W. Hillhouse, M. P. Bruce, R. D. Woody, G. Berrettini, W. H. TI Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females SO PHARMACOGENOMICS JOURNAL LA English DT Article DE buprenorphine; females; methadone; opioids; OPRD1; pharmacogenetics ID METHADONE-MAINTENANCE TREATMENT; RECEPTOR GENE; POSTOPERATIVE PAIN; GENDER-DIFFERENCES; OPIATE DEPENDENCE; RANDOMIZED-TRIAL; DRUG-DEPENDENCE; ABUSE TREATMENT; SEX-DIFFERENCES; ANALGESIA AB Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. Although these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors have a role in determining treatment outcome. This study analyses the pharmacogenetic association of six polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone (Suboxone) over the course of a 24-week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid-positive urine drug screens over the 24 weeks. In the total sample, no single-nucleotide polymorphisms (SNPs) in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed two intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (P=0.03, relative risk (RR) = 1.67, 95% confidence interval (CI) 1.06-2.1). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (P=0.006, RR =2.15, 95% CI 1.3-2.29). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be usefulwhen considering treatment options for female opioid addicts, however, confirmation in an independent sample is warranted. C1 [Clarke, T-K; Crist, R. C.; Ambrose-Lanci, L. M.; Lohoff, F. W.; Berrettini, W. H.] Univ Penn, Sch Med, Translat Res Labs, Dept Psychiat,Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. [Ang, A.; Ling, W.; Hillhouse, M. P.] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA USA. [Saxon, A. J.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Bruce, R. D.] Yale Univ, Sch Med, New Haven, CT USA. [Woody, G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Woody, G.] Treatment Res Inst, Philadelphia, PA USA. RP Clarke, TK (reprint author), Univ Penn, Sch Med, Translat Res Labs, Dept Psychiat,Ctr Neurobiol & Behav, 125 South 31st St,Room 2109, Philadelphia, PA 19104 USA. EM ctoni@mail.med.upenn.edu RI Lohoff, Falk/M-7951-2016; OI Clarke, Toni-Kim/0000-0002-7745-6351 FU National Institute on Drug Abuse through the Clinical Trials Network (CTN); Pacific Northwest Node [U10 DA01714]; Oregon Hawaii Node [U10 DA013036]; California/Arizona Node [U10 DA015815]; New England Node [U10 DA13038]; Delaware Valley Node [U10 DA13043]; Pacific Region Node [U10 DA13045]; New York Node [U10 DA013046]; Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania [T32MH014654]; NIDA [P20DA025995, P60DA05186]; Veterans Administration Mental Illness Research Education; Clinical Center MIRECC FX Main START study funding came from the National Institute on Drug Abuse through the Clinical Trials Network (CTN) through a series of grants provided to each participating node: the Pacific Northwest Node (U10 DA01714), the Oregon Hawaii Node (U10 DA013036), the California/Arizona Node (U10 DA015815), the New England Node (U10 DA13038), the Delaware Valley Node (U10 DA13043), the Pacific Region Node (U10 DA13045) and the New York Node (U10 DA013046). Dr Berrettini was also supported by the Delaware Valley Node (U10 DA13043). This work was supported by the Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, Training Program in Neuropsychopharmacology (T32MH014654, PI: I Lucki), NIDA grant P20DA025995 (PI: W Berrettini), the Veterans Administration Mental Illness Research Education and Clinical Center MIRECC) at the Philadelphia VAMC (David Oslin, MD, PI) and NIDA grant P60DA05186 (PI: Charles O'Brien). NR 51 TC 8 Z9 9 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X EI 1473-1150 J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD JUN PY 2014 VL 14 IS 3 BP 303 EP 308 DI 10.1038/tpj.2013.30 PG 6 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA AI0SK UT WOS:000336560000015 PM 24126707 ER PT J AU Lopez, J Prifogle, E Nyame, TT Milton, J May, JW AF Lopez, Joseph Prifogle, Erin Nyame, Theodore T. Milton, Jacqueline May, James W., Jr. TI The Impact of Conflicts of Interest in Plastic Surgery: An Analysis of Acellular Dermal Matrix, Implant-Based Breast Reconstruction SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID BIOMEDICAL-RESEARCH; ORTHOPEDIC RESEARCH; CLINICAL-TRIALS; PHARMACEUTICAL-INDUSTRY; ASSOCIATION; COMPLICATIONS; MODEL; SPONSORSHIP; PHYSICIANS; OUTCOMES AB Background: Although conflicts of interest in biomedical research have received significant attention, the impact of conflicts of interest on surgical outcomes has not been fully explored. Methods: A systematic electronic search of the literature was performed for studies that evaluated surgical outcomes in acellular dermal matrix and non acellular dermal matrix implant-based breast reconstruction. Surgical complications, including infection, seroma, hematoma, necrosis, and explantation, were used as outcome metrics and extracted from studies. Surgical outcomes were then pooled and compared between studies that disclosed conflicts of interest and those that did not disclose conflicts of interest. Results: A total of 776 abstracts were identified, of which only 35 fulfilled the authors' inclusion criteria. Conflicts of interest were reported in 14 of these abstracts (40 percent). The pooled data from studies that reported no conflicts of interest and studies that reported conflicts of interest included a total of 8241 and 5384 breasts and 2852 and 1864 patients, respectively. Considered collectively, surgical complications were less common in studies that reported a conflict of interest than in studies that reported no conflicts of interest. When surgical outcome data were further stratified by acellular dermal matrix use, surgical complications were less common in studies with conflicts of interest when acellular dermal matrix was used. However, when acellular dermal matrix was not used, surgical complications were similar between authors that reported a conflict of interest and those that did not report a conflict of interest. Conclusions: Self-reported conflicts of interest are common in implant-based breast reconstruction research. Studies authored by groups with conflicts of interest are significantly associated with reporting lower surgical complications and therefore describing positive research findings, especially when industry-marketed products are being used in the study. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Lopez, J (reprint author), Univ Maryland, Med Ctr, Johns Hopkins Hosp, Dept Plast Surg, 1780 East Fayette St,Bloomberg 7th Floor, Baltimore, MD 21231 USA. EM jlopez37@jhmi.edu OI Lopez, Joseph/0000-0003-3001-1109 FU TEI Biosciences FX Dr. May is a paid consultant for TEI Biosciences. Erin Prifogle, B.S., is a former employee of TEI Biosciences. The other authors have no financial disclosures to report. NR 26 TC 23 Z9 23 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 2014 VL 133 IS 6 BP 1328 EP 1334 DI 10.1097/PRS.0000000000000172 PG 7 WC Surgery SC Surgery GA AI3RK UT WOS:000336779400002 PM 24867714 ER PT J AU Reynolds, CF Thomas, SB Morse, JQ Anderson, SJ Albert, S Dew, MA Begley, A Karp, JF Gildengers, A Butters, MA Stack, JA Kasckow, J Miller, MD Quinn, SC AF Reynolds, Charles F., III Thomas, Stephen B. Morse, Jennifer Q. Anderson, Stewart J. Albert, Steven Dew, Mary Amanda Begley, Amy Karp, Jordan F. Gildengers, Ariel Butters, Meryl A. Stack, Jacqueline A. Kasckow, John Miller, Mark D. Quinn, Sandra C. TI Early Intervention to Preempt Major Depression Among Older Black and White Adults SO PSYCHIATRIC SERVICES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE DEPRESSION; PROBLEM-SOLVING THERAPY; PRIMARY-CARE PATIENTS; PREVENTING DEPRESSION; GERIATRIC DEPRESSION; RISK-FACTORS; METAANALYSIS; INVENTORY; SYMPTOMS AB Objective: The study objective was to assess the efficacy of problem-solving therapy for primary care (PST-PC) for preventing episodes of major depression and mitigating depressive symptoms of older black and white adults. The comparison group received dietary coaching. Methods: A total of 247 participants (90 blacks, 154 whites, and three Asians) with subsyndromal depressive symptoms were recruited into a randomized depression prevention trial that compared effects of individually delivered PST-PC and dietary coaching on time to major depressive episode and level of depressive symptoms (Beck Depression Inventory) over two years. Cumulative intervention time averaged 5.5-6.0 hours in each study arm. Results: The two groups did not differ significantly in time to major depressive episodes, and incidence of such episodes was low (blacks, N=8, 9%; whites, N=13, 8%), compared with published rates of 20%-25% over one year among persons with subsyndromal symptoms and receiving care as usual. Participants also showed a mean decrease of 4 points in depressive symptoms, sustained over two years. Despite greater burden of depression risk factors among blacks, no significant differences from whites were found in the primary outcome. Conclusions: Both PST-PC and dietary coaching are potentially effective in protecting older black and white adults with subsyndromal depressive symptoms from developing episodes of major depression over two years. Absent a control for concurrent usual care, this conclusion is preliminary. If confirmed, both interventions hold promise as scalable, safe, nonstigmatizing interventions for delaying or preventing episodes of major depression in the nation's increasingly diverse older population. C1 [Reynolds, Charles F., III; Morse, Jennifer Q.; Dew, Mary Amanda; Begley, Amy; Karp, Jordan F.; Gildengers, Ariel; Butters, Meryl A.; Stack, Jacqueline A.; Kasckow, John; Miller, Mark D.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. [Kasckow, John] Vet Affairs Pittsburgh Hlth Care Syst, Dept Behav Hlth, Pittsburgh, PA USA. [Thomas, Stephen B.; Quinn, Sandra C.] Univ Maryland, Ctr Hlth Equ, College Pk, MD 20742 USA. [Anderson, Stewart J.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Albert, Steven] Univ Pittsburgh, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. RP Reynolds, CF (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. EM reynoldscf@upmc.edu OI Anderson, Stewart/0000-0001-8948-0650; Albert, Steven/0000-0001-6786-9956 FU National Institute of Mental Health [P60 MD000207, P30 MH090333, UL1RR024153, UL1TR000005]; National Institutes of Health; University of Pittsburgh Medical Center Endowment in Geriatric Psychiatry; Commonwealth of Pennsylvania; Bristol-Myers Squibb; Forest; Pfizer; Lilly; Robert Bosch Health Care, Inc. FX This work was supported by grants P60 MD000207, P30 MH090333, UL1RR024153, and UL1TR000005 from the National Institute of Mental Health and National Institutes of Health, by the University of Pittsburgh Medical Center Endowment in Geriatric Psychiatry, and by the Commonwealth of Pennsylvania. This work is registered on ClinicalTrials.gov as NCT00326677.; Dr. Reynolds reports receiving pharmaceutical support for National Institutes of Health sponsored research studies from Bristol-Myers Squibb, Forest, Pfizer, and Lilly. He is the co-inventor of Psychometric Analysis of the Pittsburgh Sleep Quality Index (licensed intellectual property PRO10050447). Dr. Karp reports receipt of medication supplies from Pfizer and Reckitt Benckiser for investigator-initiated studies. Dr. Butters has received remuneration from GlaxoSmithKline for performing neuropsychological services. Dr. Kasckow has received assistance from Robert Bosch Health Care, Inc., for software-related costs for a research project. The other authors report no competing interests. NR 37 TC 14 Z9 14 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JUN PY 2014 VL 65 IS 6 BP 765 EP 773 DI 10.1176/appi.ps.201300216 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA AI3RJ UT WOS:000336779300009 PM 24632760 ER PT J AU Cheung, OS Bar, M AF Cheung, Olivia S. Bar, Moshe TI The resilience of object predictions: Early recognition across viewpoints and exemplars SO PSYCHONOMIC BULLETIN & REVIEW LA English DT Article DE Object recognition; Repetition priming; Spatial frequency ID UNDERLIE REPETITION SUPPRESSION; TOP-DOWN FACILITATION; SPATIAL-FREQUENCIES; FUSIFORM CORTEX; NEURAL MECHANISMS; ROTATED OBJECTS; CATEGORIZATION; SCENE; ORIENTATION; INFORMATION AB Recognition of everyday objects can be facilitated by top-down predictions. We have proposed that these predictions are derived from rudimentary image information, or gist, extracted rapidly from the low spatial frequencies (LSFs) (Bar Journal of Cognitive Neuroscience 15: 600-609, 2003). Because of the coarse nature of LSF representations, we hypothesized here that such predictions can accommodate changes in viewpoint as well as facilitate the recognition of visually similar objects. In a repetition-priming task, we indeed observed significant facilitation of target recognition that was primed by LSF objects across moderate viewpoint changes, as well as across visually similar exemplars. These results suggest that the LSF representations are specific enough to activate accurate predictions, yet flexible enough to overcome small changes in visual appearance. Such gist representations facilitate object recognition by accommodating changes in visual appearance due to viewing conditions, and help generalize from familiar to novel exemplars. C1 [Cheung, Olivia S.; Bar, Moshe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr, Boston, MA USA. [Bar, Moshe] Bar Ilan Univ, Gonda Ctr Multidisciplinary Brain Res, Ramat Gan, Israel. [Cheung, Olivia S.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Cheung, OS (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM sccheung.olivia@gmail.com FU NEI NIH HHS [1R01EY019477-01, R01 EY019477] NR 47 TC 4 Z9 4 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1069-9384 EI 1531-5320 J9 PSYCHON B REV JI Psychon. Bull. Rev. PD JUN PY 2014 VL 21 IS 3 BP 682 EP 688 DI 10.3758/s13423-013-0546-5 PG 7 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA AH8XZ UT WOS:000336422800012 PM 24234168 ER PT J AU Provencher, CDRMT Makani, A McNeil, JW Pomerantz, ML Golijanin, P Gross, D AF Provencher, C. D. R. Matthew T. Makani, Amun McNeil, John W. Pomerantz, M. Lucius Golijanin, Petar Gross, Daniel TI The Role of the Scapula in Throwing Disorders SO SPORTS MEDICINE AND ARTHROSCOPY REVIEW LA English DT Review DE throwing shoulder; scapular dyskinesis; GIRD; impingement; scapula; mechanics ID PROFESSIONAL BASEBALL PITCHERS; INTERNAL-ROTATION DEFICIT; SHOULDER IMPINGEMENT; MUSCLE FATIGUE; PART 1; MOTION; KINEMATICS; DYSKINESIS; PROTRACTION; ELEVATION AB Shoulder injuries in the thrower can prove a challenge to diagnose and treat. Overhead throwing is an intricate motion that places considerable torque on the shoulder. The complex interplay of the scapula with the glenohumeral joint and its surrounding musculature allows elite pitchers to achieve speeds >95 miles per hour. An understanding of scapular motion is integral to diagnose and treat shoulder pathology in these athletes. Treatment is aimed at addressing the underlying cause with a physical rehabilitation program. Although nonoperative care is the most predictable and useful treatment, occasionally operative treatment is necessary. This chapter will outline normal scapular motion during throwing, the effects of common shoulder disorders on throwing mechanics, and the prevention, diagnosis, and treatment of these conditions. C1 [Provencher, C. D. R. Matthew T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Makani, Amun; Golijanin, Petar; Gross, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McNeil, John W.] Univ Calif San Diego, Sch Med, San Diego, CA USA. [Pomerantz, M. Lucius] Univ Calif San Diego, Sch Med, Dept Orthoped Surg, San Diego, CA USA. RP Provencher, CDRMT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 175 Cambridge St,Suite 400, Boston, MA 02114 USA. NR 39 TC 1 Z9 1 U1 3 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-8592 EI 1538-1951 J9 SPORTS MED ARTHROSC JI Sports Med. Arthrosc. Rev. PD JUN PY 2014 VL 22 IS 2 BP 80 EP 87 DI 10.1097/JSA.0000000000000023 PG 8 WC Sport Sciences SC Sport Sciences GA AH9ZS UT WOS:000336506000003 PM 24787721 ER PT J AU Engels, MC Rajarajan, K Feistritzer, R Sharma, A Nielsen, UB Schalij, MJ de Vries, AAF Pijnappels, DA Wu, SM AF Engels, Marc C. Rajarajan, Kuppusamy Feistritzer, Rebecca Sharma, Arun Nielsen, Ulrik B. Schalij, Martin J. de Vries, Antoine A. F. Pijnappels, Daniel A. Wu, Sean M. TI Insulin-Like Growth Factor Promotes Cardiac Lineage Induction In Vitro by Selective Expansion of Early Mesoderm SO STEM CELLS LA English DT Article DE Embryonic stem cell; Development; Mesoderm; Cardiac progenitor cell; Cardiomyocyte; Cardiac differentiation; In vitro screening; Insulin; Insulin-like growth factor; Akt ID EMBRYONIC STEM-CELLS; PROGENITOR CELLS; CARDIOMYOCYTE PROLIFERATION; SIGNALING EXERTS; SMOOTH-MUSCLE; DIFFERENTIATION; HEART; BMP; CARDIOMYOGENESIS; PATHWAY AB A thorough understanding of the developmental signals that direct pluripotent stem cells (PSCs) toward a cardiac fate is essential for translational applications in disease modeling and therapy. We screened a panel of 44 cytokines/signaling molecules for their ability to enhance Nkx2.5(+) cardiac progenitor cell (CPC) formation during in vitro embryonic stem cell (ESC) differentiation. Treatment of murine ESCs with insulin or insulin-like growth factors (IGF1/2) during early differentiation increased mesodermal cell proliferation and, consequently, CPC formation. Furthermore, we show that downstream mediators of IGF signaling (e. g., phospho-Akt and mTOR) are required for this effect. These data support a novel role for IGF family ligands to expand the developing mesoderm and promote cardiac differentiation. Insulin or IGF treatment could provide an effective strategy to increase the PSC-based generation of CPCs and cardiomyocytes for applications in regenerative medicine. C1 [Engels, Marc C.; Rajarajan, Kuppusamy; Feistritzer, Rebecca; Wu, Sean M.] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. [Engels, Marc C.; Schalij, Martin J.; de Vries, Antoine A. F.; Pijnappels, Daniel A.] Leiden Univ, Lab Expt Cardiol, Dept Cardiol, Heart Ctr Leiden,Med Ctr, Leiden, Netherlands. [Sharma, Arun] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Nielsen, Ulrik B.] Silver Creek Pharmaceut Inc, San Francisco, CA USA. [Wu, Sean M.] Harvard Stem Cell Inst, Cambridge, MA USA. RP Wu, SM (reprint author), Stanford Univ, Div Cardiovasc Med, Sch Med, Dept Med,Stanford Cardiovasc Inst, 265 Campus Dr, Stanford, CA 94305 USA. EM smwu@stanford.edu FU NIH [NS069375]; Netherlands Organization for Scientific Research [NWO 017.007.064]; NWO (VENI grant) [91611070]; NIH/Officer of the Director's New Innovator Award [OD004411]; NIH/NHLBI [HL099776, HL081086]; Harvard Stem Cell Institute FX Laura Prickett-Rice and Katherine Folz-Donahue at the Center for Regenerative Medicine Harvard Stem Cell Institute Flow Cytometry Core provided assistance with flow cytometry experiments. Andrew Olson at the Stanford Neuroscience Microscopy Service (supported by NIH NS069375) at Stanford School of Medicine provided technical assistance with confocal microscopy imaging. M.C.E. was supported by a Mosaic grant from the Netherlands Organization for Scientific Research (NWO 017.007.064). D.A.P. was supported by NWO (VENI grant 91611070) and S.M.W. was supported by NIH/Officer of the Director's New Innovator Award (OD004411), NIH/NHLBI U01 (HL099776) and K08 (HL081086) and by the Harvard Stem Cell Institute. NR 38 TC 11 Z9 11 U1 0 U2 6 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 JUN PY 2014 VL 32 IS 6 BP 1493 EP 1502 DI 10.1002/stem.1660 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA AI3EE UT WOS:000336741700014 PM 24496962 ER PT J AU Seible, DM Gu, XM Hyatt, AS Beard, CJ Choueiri, TK Efstathiou, JA Miyamoto, DT Mitin, T Martin, NE Sweeney, CJ Trinh, QD Beckman, JA Basaria, S Nguyen, PL AF Seible, Daniel M. Gu, Xiangmei Hyatt, Andrew S. Beard, Clair J. Choueiri, Toni K. Efstathiou, Jason A. Miyamoto, David T. Mitin, Timur Martin, Neil E. Sweeney, Christopher J. Trinh, Quoc-Dien Beckman, Joshua A. Basaria, Shehzad Nguyen, Paul L. TI Weight Gain on Androgen Deprivation Therapy: Which Patients Are at Highest Risk? SO UROLOGY LA English DT Article ID PROSTATE-CANCER; BODY-COMPOSITION; MEN; AGE; SUPPRESSION; METAANALYSIS; CARCINOMA; EXERCISE; HORMONES; MALES AB OBJECTIVE To identify factors associated with weight gain at 1 year from initiation of androgen deprivation therapy (ADT). METHODS A retrospective review assessed weight change among 118 men with nonmetastatic prostate cancer treated with ADT for at least 6 months. Outcome associations were tested using 2-tailed t tests and linear regression. RESULTS Men in our cohort had significant weight gain (1.32 kg, P = .0005) in the 1 year after ADT initiation. Three risk factors for weight gain on ADT were identified as follows: age < 65 years (2.72 kg gained, P = .001), body mass index (BMI) < 30 (1.98 kg gained, P = .00002), and nondiabetic status (1.56 kg gained, P = .0003). Multivariable regression found both age < 65 years (beta = 4.01, P = .02) and BMI <30 (beta = 3.57, P = .03) to be independently predictive of weight gain, whereas nondiabetic status was nonsignificantly predictive of weight gain (beta = 2.14, P = .29). Weight change was further stratified by the total number of risk factors present (risk score): scores of 0, 1, 2, and 3 risk factors corresponded to weight changes of -1.10, +0.41, +1.34, and +3.79 kg, respectively (P-trend = .0005). CONCLUSION Age < 65 years and BMI < 30 were both independently associated with weight gain 1 year after starting ADT. Increasing weight gain was also strongly associated with increasing number of baseline risk factors present. Despite traditional concerns about ADT in unhealthy men, these data suggest younger, healthier patients may be at higher risk for gaining weight on ADT and should be counseled accordingly. (C) 2014 Elsevier Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Seible, DM (reprint author), Brigham & Womens Hosp, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM daniel_seible@hms.harvard.edu RI Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Beckman, Joshua/0000-0001-8332-8439 FU Prostate Cancer Foundation; Fitz's Cancer Warriors FX This work is supported by the Prostate Cancer Foundation, Fitz's Cancer Warriors, David and Cynthia Chapin, and a grant from an Anonymous Family Foundation. NR 28 TC 5 Z9 5 U1 0 U2 1 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 JUN PY 2014 VL 83 IS 6 BP 1316 EP 1321 DI 10.1016/j.urology.2014.02.006 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA AI0DL UT WOS:000336516300020 PM 24726149 ER PT J AU El-Serag, HB Sweet, S Winchester, CC Dent, J AF El-Serag, Hashem B. Sweet, Stephen Winchester, Christopher C. Dent, John TI Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review SO GUT LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; QUALITY-OF-LIFE; RISK-FACTORS; CLINICAL SPECTRUM; GENERAL-POPULATION; BARRETTS-ESOPHAGUS; ADULT-POPULATION; PRIMARY-CARE; PREVALENCE; SYMPTOMS AB Objective To update the findings of the 2005 systematic review of population-based studies assessing the epidemiology of gastro-oesophageal reflux disease (GERD). Design PubMed and Embase were screened for new references using the original search strings. Studies were required to be population-based, to include >= 200 individuals, to have response rates >= 50% and recall periods < 12 months. GERD was defined as heartburn and/or regurgitation on at least 1 day a week, or according to the Montreal definition, or diagnosed by a clinician. Temporal and geographic trends in disease prevalence were examined using a Poisson regression model. Results 16 studies of GERD epidemiology published since the original review were found to be suitable for inclusion (15 reporting prevalence and one reporting incidence), and were added to the 13 prevalence and two incidence studies found previously. The range of GERD prevalence estimates was 18.1%-27.8% in North America, 8.8%-25.9% in Europe, 2.5%-7.8% in East Asia, 8.7%-33.1% in the Middle East, 11.6% in Australia and 23.0% in South America. Incidence per 1000 person-years was approximately 5 in the overall UK and US populations, and 0.84 in paediatric patients aged 117 years in the UK. Evidence suggests an increase in GERD prevalence since 1995 (p<0.0001), particularly in North America and East Asia. Conclusions GERD is prevalent worldwide, and disease burden may be increasing. Prevalence estimates show considerable geographic variation, but only East Asia shows estimates consistently lower than 10%. C1 [El-Serag, Hashem B.] Houston Vet Affairs Med Ctr 152, Sect Gastroenterol & Hepatol, Houston, TX USA. [Sweet, Stephen; Winchester, Christopher C.] Oxford PharmaGenesis, Res Evaluat Unit, Oxford, England. [Winchester, Christopher C.] Univ Aberdeen, Ctr Acad Primary Care, Aberdeen, Scotland. [Dent, John] Royal Adelaide Hosp, Dept Gastroenterol Hepatol & Gen Med, Adelaide, SA 5000, Australia. RP El-Serag, HB (reprint author), Houston VA Med Ctr, Sect Gastroenterol & Hepatol, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.edu OI Winchester, Christopher/0000-0003-3267-3990 FU Texas Digestive Disease Center [NIH DK58338, NIDDK K24-04-107]; Houston VA Health Services R&D Center of Excellence [HFP90-020]; AstraZeneca R&D, Molndal, Sweden FX This work was supported in part by Texas Digestive Disease Center grants NIH DK58338 and NIDDK K24-04-107 to Dr El-Serag and by the Houston VA Health Services R&D Center of Excellence (HFP90-020). The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs. Stephen Sweet and Christopher C Winchester are employees of Oxford PharmaGenesis, which received funding from AstraZeneca R&D, Molndal, Sweden for its role in the preparation of this systematic review. NR 49 TC 154 Z9 167 U1 3 U2 22 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 JUN PY 2014 VL 63 IS 6 BP 871 EP 880 DI 10.1136/gutjnl-2012-304269 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA AG4AB UT WOS:000335360000006 PM 23853213 ER PT J AU Araki, T Sholl, LM Gerbaudo, VH Hatabu, H Nishino, M AF Araki, Tetsuro Sholl, Lynette M. Gerbaudo, Victor H. Hatabu, Hiroto Nishino, Mizuki TI Thymic Measurements in Pathologically Proven Normal Thymus and Thymic Hyperplasia: Intraobserver and Interobserver Variabilities SO ACADEMIC RADIOLOGY LA English DT Article DE Thymus; computed tomography; measurement; intraobserver variability; interobserver variability ID CELL LUNG-CANCER; AGE-RELATED-CHANGES; COMPUTED-TOMOGRAPHY; ABNORMAL THYMUS AB Rationale and Objectives: To determine the intraobserver and interobserver variabilities of thymic measurements on computed tomography (CT) in patients with pathologic diagnosis of thymic hyperplasia or normal thymus. Materials and Methods: Thirty-three patients with pathologic diagnosis of thymic hyperplasia (n = 25) or normal thymus (n = 8) who had identifiable thymus gland on CT were retrospectively studied. Two radiologists independently measured thymic size and CT attenuation. Concordance correlation coefficients (CCCs) and Bland-Altman plots were used to assess intraobserver and interobserver agreements. Results: The intraobserver and interobserver agreements of thymic diameters and the lobe length were moderate, with CCCs ranging from 0.73 to 0.89 and from 0.72 to 0.81, respectively. Higher agreement was noted among patients whose measurements were performed on the same CT image in two independent measurements, with intraobserver CCC >= 0.95 for diameters and length. After providing readers with an instruction for consistent selection of CT image for measurements, the intraobserver and interobserver agreements improved, resulting in CCCs ranging from 0.81 to 0.92 and from 0.77 to 0.85 for diameters and length, respectively. Thymic lobe thickness had the least agreement. CT attenuation measurements were highly reproducible, with CCCs ranging from 0.88 to 0.97. In patients with thymic CT attenuation >30 HU (Hounsfield unit), the attenuation measurements were more reproducible with narrower 95% limits of agreement. Conclusions: Thymic size measurements had moderate-to-high intraobserver and interobserver agreements, when the instruction for consistent selection of images was provided to the readers. CT attenuation was highly reproducible, with higher reproducibility for thymic glands with >30 HU. Awareness of thymic measurement variability is necessary when interpreting measured values of normal thymus and thymic pathology on CT. C1 [Araki, Tetsuro; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. [Nishino, Mizuki] Harvard Univ, Sch Med, Dept Imaging, Dana Farber Canc Inst, Boston, MA 02215 USA. [Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. RP Nishino, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02215 USA. EM Mizuki_Nishino@DFCI.HARVARD.EDU FU National Cancer Institute [1K23CA157631] FX The investigator, M.N. was supported by grant 1K23CA157631 from National Cancer Institute. NR 21 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 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD JUN PY 2014 VL 21 IS 6 BP 733 EP 742 DI 10.1016/j.acra.2014.02.006 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH8UQ UT WOS:000336414100006 PM 24809315 ER PT J AU Martin, JT Milby, AH Chiaro, JA Kim, DH Hebela, NM Smith, LJ Elliott, DM Mauck, RL AF Martin, John T. Milby, Andrew H. Chiaro, Joseph A. Kim, Dong Hwa Hebela, Nader M. Smith, Lachlan J. Elliott, Dawn M. Mauck, Robert L. TI Translation of an engineered nanofibrous disc-like angle-ply structure for intervertebral disc replacement in a small animal model SO ACTA BIOMATERIALIA LA English DT Article DE Intervertebral disc; Tissue engineering; Electrospinning; Surgical model; External fixation ID HUMAN LUMBAR DISC; LOW-BACK-PAIN; ANNULUS FIBROSUS; BIOMECHANICAL FUNCTION; DYNAMIC COMPRESSION; LOADING IMPROVES; NUCLEUS PULPOSUS; ANULUS FIBROSUS; NEEDLE PUNCTURE; SCAFFOLDS AB Intervertebral disc degeneration has been implicated in the etiology of low back pain; however, the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF) and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(epsilon-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, can achieve functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle-ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilized the motion segment via external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the pen-implant space and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements. (C) 2014 Acts Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Martin, John T.; Milby, Andrew H.; Chiaro, Joseph A.; Kim, Dong Hwa; Hebela, Nader M.; Smith, Lachlan J.; Mauck, Robert L.] Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. [Martin, John T.; Mauck, Robert L.] Univ Penn, Dept Mech Engn & Appl Mech, Philadelphia, PA 19104 USA. [Elliott, Dawn M.] Univ Delaware, Dept Biomed Engn, Newark, DE 19716 USA. [Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Martin, John T.; Milby, Andrew H.; Chiaro, Joseph A.; Hebela, Nader M.; Smith, Lachlan J.; Mauck, Robert L.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA. [Smith, Lachlan J.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. RP Mauck, RL (reprint author), Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, 36th St & Hamilton Walk,424 Stemmler Hall, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu FU Department of Defense [OR090090]; Department of Veterans Affairs [I01RX000211] FX We would like to thank the exceptional staff of the Philadelphia VA Medical Center Animal Research Facility: Debra Pawlowski, Jeffrey House and Pierina Deritis. In addition we would like to thank Deborah Gorth and Feini Qu (animal procedures), Alexei Adan (DAPS fabrication and histology), Subash Poudel (DAPS geometry and mechanical property measurements), Sophia Stylianos (fabrication of surgical equipment) and Dr. Thomas Schaer (sterilization facilities). This work was funded by the Department of Defense (Grant #OR090090) and the Department of Veterans Affairs (Grant # I01RX000211). NR 49 TC 15 Z9 18 U1 6 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 EI 1878-7568 J9 ACTA BIOMATER JI Acta Biomater. PD JUN PY 2014 VL 10 IS 6 BP 2473 EP 2481 DI 10.1016/j.actbio.2014.02.024 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AH7WK UT WOS:000336345900012 PM 24560621 ER PT J AU Chan, KMC Li, RH Chapman, JW Trac, EM Kobler, JB Zeitels, SM Langer, R Karajanagi, SS AF Chan, Ka Man Carmen Li, Randolph H. Chapman, Joseph W. Trac, Eric M. Kobler, James B. Zeitels, Steven M. Langer, Robert Karajanagi, Sandeep S. TI Functionalizable hydrogel microparticles of tunable size and stiffness for soft-tissue filler applications SO ACTA BIOMATERIALIA LA English DT Article DE Soft-tissue filler; Hydrogel; Microparticles; Suspension photopolymerization ID ACID DERMAL FILLERS; HYALURONIC-ACID; SUSPENSION POLYMERIZATION; CALCIUM HYDROXYLAPATITE; RHEOLOGICAL PROPERTIES; INJECTABLE FILLERS; FLOW LITHOGRAPHY; IN-VIVO; PARTICLES; CELLS AB Particle size, stiffness and surface functionality are important in determining the injection site, safety and efficacy of injectable soft-tissue fillers. Methods to produce soft injectable biomaterials with controlled particle characteristics are therefore desirable. Here we report a method based on suspension photopolymerization and semi-interpenetrating network (semi-IPN) to synthesize soft, functionalizable, spherical hydrogel microparticles (MP) of independently tunable size and stiffness. MP were prepared using acrylated forms of polyethylene glycol (PEG), gelatin and hyaluronic acid. Semi-IPN MP of PEG-diacrylate and PEG were used to study the effect of process parameters on particle characteristics. The process parameters were systematically varied to produce MP with size ranging from 115 to 515 JAM and stiffness ranging from 190 to 1600 Pa. In vitro studies showed that the MP thus prepared were cytocompatible. The ratio and identity of the polymers used to make the semi-IPN MP were varied to control their stiffness and to introduce amine groups for potential functionalization. Slow-release polymeric particles loaded with Rhodamine or dexamethasone were incorporated in the MP as a proof-of-principle of drug incorporation and release from the MP. This work has implications in preparing injectable biomaterials of natural or synthetic polymers for applications as soft-tissue fillers. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Chan, Ka Man Carmen; Li, Randolph H.; Chapman, Joseph W.; Kobler, James B.; Zeitels, Steven M.; Karajanagi, Sandeep S.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Chan, Ka Man Carmen; Li, Randolph H.; Trac, Eric M.; Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Karajanagi, SS (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 70 Blossom St, Boston, MA 02114 USA. EM skarajanagi@partners.org FU Voice Health Institute FX We thank Matias Porras Paniagua and Keriann Durgin for assistance with drug release studies and Dr. Jie Zhao for assistance with confocal microscopy. This work was funded by the Voice Health Institute. NR 57 TC 8 Z9 8 U1 7 U2 62 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 EI 1878-7568 J9 ACTA BIOMATER JI Acta Biomater. PD JUN PY 2014 VL 10 IS 6 BP 2563 EP 2573 DI 10.1016/j.actbio.2014.02.021 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA AH7WK UT WOS:000336345900020 PM 24561708 ER PT J AU Caretti, V Sewing, ACP Lagerweij, T Schellen, P Bugiani, M Jansen, MHA van Vuurden, DG Navis, AC Horsman, I Vandertop, WP Noske, DP Wesseling, P Kaspers, GJL Nazarian, J Vogel, H Hulleman, E Monje, M Wurdinger, T AF Caretti, Viola Sewing, A. Charlotte P. Lagerweij, Tonny Schellen, Pepijn Bugiani, Marianna Jansen, Marc H. A. van Vuurden, Dannis G. Navis, Anna C. Horsman, Ilona Vandertop, W. Peter Noske, David P. Wesseling, Pieter Kaspers, Gertjan J. L. Nazarian, Javad Vogel, Hannes Hulleman, Esther Monje, Michelle Wurdinger, Thomas TI Human pontine glioma cells can induce murine tumors SO ACTA NEUROPATHOLOGICA LA English DT Article DE Neoplasms; Pontine neoplasms; Animal disease model; Microglia ID BRAIN-STEM GLIOMAS; HIGH-GRADE GLIOMAS; NUDE-MICE; MALIGNANT TRANSFORMATION; PEDIATRIC GLIOBLASTOMA; CLINICAL-TRIALS; HISTONE H3.3; HOST-CELLS; IN-VITRO; FUSION AB Diffuse intrinsic pontine glioma (DIPG), with a median survival of only 9 months, is the leading cause of pediatric brain cancer mortality. Dearth of tumor tissue for research has limited progress in this disease until recently. New experimental models for DIPG research are now emerging. To develop preclinical models of DIPG, two different methods were adopted: cells obtained at autopsy (1) were directly xenografted orthotopically into the pons of immunodeficient mice without an intervening cell culture step or (2) were first cultured in vitro and, upon successful expansion, injected in vivo. Both strategies resulted in pontine tumors histopathologically similar to the original human DIPG tumors. However, following the direct transplantation method all tumors proved to be composed of murine and not of human cells. This is in contrast to the indirect method that included initial in vitro culture and resulted in xenografts comprising human cells. Of note, direct injection of cells obtained postmortem from the pons and frontal lobe of human brains not affected by cancer did not give rise to neoplasms. The murine pontine tumors exhibited an immunophenotype similar to human DIPG, but were also positive for microglia/macrophage markers, such as CD45, CD68 and CD11b. Serial orthotopic injection of these murine cells results in lethal tumors in recipient mice. Direct injection of human DIPG cells in vivo can give rise to malignant murine tumors. This represents an important caveat for xenotransplantation models of DIPG. In contrast, an initial in vitro culture step can allow establishment of human orthotopic xenografts. The mechanism underlying this phenomenon observed with direct xenotransplantation remains an open question. C1 [Caretti, Viola; Monje, Michelle] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA. [Caretti, Viola; Monje, Michelle] Stanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USA. [Caretti, Viola; Monje, Michelle] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. [Caretti, Viola; Sewing, A. Charlotte P.; Lagerweij, Tonny; Schellen, Pepijn; Jansen, Marc H. A.; van Vuurden, Dannis G.; Kaspers, Gertjan J. L.; Hulleman, Esther] Vrije Univ Amsterdam, Med Ctr, Dept Pediat Oncol, Amsterdam, Netherlands. [Caretti, Viola; Sewing, A. Charlotte P.; Lagerweij, Tonny; Schellen, Pepijn; Vandertop, W. Peter; Noske, David P.; Hulleman, Esther; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Amsterdam, Netherlands. [Caretti, Viola; Sewing, A. Charlotte P.; Lagerweij, Tonny; Schellen, Pepijn; Jansen, Marc H. A.; van Vuurden, Dannis G.; Noske, David P.; Wesseling, Pieter; Hulleman, Esther; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Neurooncol Res Grp, Amsterdam, Netherlands. [Caretti, Viola; Monje, Michelle] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Bugiani, Marianna; Wesseling, Pieter] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. [Navis, Anna C.; Wesseling, Pieter] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands. [Horsman, Ilona] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Nazarian, Javad] Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. [Vogel, Hannes] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [Hulleman, Esther; Wurdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands. [Wurdinger, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Caretti, V (reprint author), Stanford Univ, Sch Med, 265 Campus Dr,Room G3077, Stanford, CA 94305 USA. EM vcaretti@stanford.edu; e.hulleman@vumc.nl; mmonje@stanford.edu; t.wurdinger@vumc.nl RI Wesseling, P./H-8114-2014; OI Wesseling, P./0000-0001-5453-5201; Lagerweij, Tonny/0000-0003-1043-7452; Vogel, Otto Hannes/0000-0002-0960-3508; Navis, Anna/0000-0002-5267-4678; Van Vuurden, Dannis/0000-0002-1364-9007 FU NIH [1S10RR02933801]; Semmy Foundation; KiKa Children Cancer Free; Child Health Research Institute; Lucile Packard Foundation for Children's Health; Stanford CTSA [UL1 TR000093]; Stanford University School of Medicine Dean's Fellowship; National Institutes of Neurological Disease and Stroke (NINDS) [K08NS070926]; Alex's Lemonade Stand Foundation; McKenna Claire Foundation; The Cure Starts Now; Lyla Nsouli Foundation; Connor Johnson Memorial Fund; Dylan Jewett Memorial Fund; Dylan Frick Memorial Fund; Abigail Jensen Memorial Fund; Zoey Ganesh Memorial Fund; Wayland Villars Memorial Fund; Musella Foundation FX We would like to thank the patients and families who so generously donated tissue for this research. We sincerely thank the architect and artist Alessandra Luoni for drawing Fig. 1a. We gracefully acknowledge Alyssa Noll (Departments of Neurology and Pediatrics) for support with animal experiments, and Patty Lovelace (FACS Core) for her expertise with flow cytometry experiments; all from Stanford, USA. The flow cytometer used was purchased using an NIH S10 Shared Instrumentation Grant (1S10RR02933801). We are thankful to Jacqueline Cloos (Department of Pediatric Oncology, VU University Medical Center, The Netherlands) and Dana Bangs (Cytogenetics Laboratory, Stanford, USA) for their mastery in analyzing metaphase spreads. We are also thankful to Sridevi Yadavilli for processing postmortem specimens and assisting in murine injections, Research Center for Genetic Medicine, Children's National Medical Center, Washington, USA. This work was supported by the Semmy Foundation, KiKa Children Cancer Free, Child Health Research Institute, Lucile Packard Foundation for Children's Health, as well as the Stanford CTSA-award number UL1 TR000093-(V.C.), Stanford University School of Medicine Dean's Fellowship (V. C.), National Institutes of Neurological Disease and Stroke (NINDS grant K08NS070926), Alex's Lemonade Stand Foundation, McKenna Claire Foundation, The Cure Starts Now, Lyla Nsouli Foundation, Connor Johnson Memorial Fund, Dylan Jewett Memorial Fund, Dylan Frick Memorial Fund, Abigail Jensen Memorial Fund, Zoey Ganesh Memorial Fund, Wayland Villars Memorial Fund and Musella Foundation. NR 54 TC 12 Z9 12 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JUN PY 2014 VL 127 IS 6 BP 897 EP 909 DI 10.1007/s00401-014-1272-4 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA AH6WO UT WOS:000336273100008 PM 24777482 ER PT J AU Scherzer, R Gandhi, M Estrella, MM Tien, PC Deeks, SG Grunfeld, C Peralta, CA Shlipak, MG AF Scherzer, Rebecca Gandhi, Monica Estrella, Michelle M. Tien, Phyllis C. Deeks, Steven G. Grunfeld, Carl Peralta, Carmen A. Shlipak, Michael G. TI A chronic kidney disease risk score to determine tenofovir safety in a prospective cohort of HIV-positive male veterans SO AIDS LA English DT Article DE chronic kidney disease; HIV; risk score; tenofovir ID INFECTED PATIENTS; RANDOMIZED-TRIAL; RENAL-FAILURE; CYSTATIN-C; THERAPY; INDIVIDUALS; ALBUMINURIA; ASSOCIATION; DYSFUNCTION; EXPOSURE AB Objective:Tenofovir disoproxil fumarate is a widely used antiretroviral for HIV infection that has been associated with an increased risk of chronic kidney disease (CKD). Our objective was to derive a scoring system to predict 5-year risk of developing CKD in HIV-infected individuals and to estimate difference in risk associated with tenofovir use.Design:We evaluated time to first occurrence of CKD (estimated glomerular filtration rate <60ml/min per 1.73m(2)) in 21590 HIV-infected men from the Veterans Health Administration initiating antiretroviral therapy from 1997 to 2010.Methods:We developed a point-based score using multivariable Cox regression models. Median follow-up was 6.3 years, during which 2059 CKD events occurred.Results:Dominant contributors to the CKD risk score were traditional kidney risk factors (age, glucose, SBP, hypertension, triglycerides, proteinuria); CD4(+) cell count was also a component, but not HIV RNA. The overall 5-year event rate was 7.7% in tenofovir users and 3.8% in nonusers [overall adjusted hazard ratio 2.0, 95% confidence interval (CI) 1.8-2.2]. There was a progressive increase in 5-year CKD risk, ranging from less than 1% (zero points) to 16% (9 points) in nonusers of tenofovir, and from 1.4 to 21.4% among tenofovir users. The estimated number-needed-to-harm (NNH) for tenofovir use ranged from 108 for those with zero points to 20 for persons with at least nine points. Among tenofovir users with at least 1 year exposure, NNH ranged from 68 (zero points) to five (9 points).Conclusion:The CKD risk score can be used to predict an HIV-infected individual's absolute risk of developing CKD over 5 years and may facilitate clinical decision-making around tenofovir use. C1 [Scherzer, Rebecca; Gandhi, Monica; Tien, Phyllis C.; Deeks, Steven G.; Grunfeld, Carl; Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Scherzer, Rebecca; Tien, Phyllis C.; Grunfeld, Carl; Peralta, Carmen A.; Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. [Gandhi, Monica; Deeks, Steven G.] San Francisco Gen Hosp, Posit Hlth Program, San Francisco, CA 94110 USA. [Estrella, Michelle M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Shlipak, MG (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM michael.shlipak@ucsf.edu FU National Institutes of Health [K23DK080645-01A1, 1R03AG034871-01, K24AI069994, R01 DK066488-01, RO1 AI098472]; National Center for Research Resources [KL2 RR024130]; American Heart Association Established Investigator Award; VA Public Health Strategic Healthcare Group; Gilead; Merck; Bristol-Myers Squibb; Abbott; Gilead Sciences; EMD Serono; Theratechnologies FX This work was supported by the National Institutes of Health [K23DK080645-01A1 (A. I. C.), 1R03AG034871-01 (A.I.C./M.G.S.), K24AI069994, R01 DK066488-01 (M.G.S./A.I.C.), RO1 AI098472 (M. G.)], the National Center for Research Resources [KL2 RR024130], the American Heart Association Established Investigator Award (M.G.S.) and the VA Public Health Strategic Healthcare Group, which were administered by the Northern California Institute for Research and Education, and with resources of the Veterans Affairs Medical Center, San Francisco, California. These funding sources had no involvement in the design or execution of this study. S. G. D. received grant support from Gilead and Merck, and honorarium for ad hoc consulting from Gilead and GlaxoSmithKline. C.G. has received prior research funding and/or honorarium from Merck, Bristol-Myers Squibb, Abbott, Gilead Sciences, EMD Serono and Theratechnologies. NR 30 TC 9 Z9 9 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUN 1 PY 2014 VL 28 IS 9 BP 1289 EP 1295 DI 10.1097/QAD.0000000000000258 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA AH2SX UT WOS:000335972500006 PM 24922479 ER PT J AU Blashill, AJ Wilson, JM Baker, JS Mayer, KH Safren, SA AF Blashill, Aaron J. Wilson, Johannes M. Baker, Joshua S. Mayer, Kenneth H. Safren, Steven A. TI Assessing Appearance-Related Disturbances in HIV-Infected Men Who have Sex with Men (MSM): Psychometrics of the Body Change and Distress Questionnaire-Short Form (ABCD-SF) SO AIDS AND BEHAVIOR LA English DT Article DE HIV; MSM; Body image disturbance; Scale development; Health outcomes ID QUALITY-OF-LIFE; ACTIVE ANTIRETROVIRAL THERAPY; STRUCTURAL EQUATION MODELS; SMALL SAMPLE-SIZES; FACIAL LIPOATROPHY; BISEXUAL MEN; IMAGE; LIPODYSTROPHY; ADHERENCE; HEALTH AB Appearance-related disturbances are common among HIV-infected MSM; however, to date, there have been limited options in the valid assessment of this construct. The aim of the current study was to assess the structural, internal, and convergent validity of the assessment of body change distress questionnaire (ABCD) and its short version. Exploratory and confirmatory factor analyses indicated that both versions fit the data well. Four subfactors were revealed measuring the following body disturbance constructs: (1) negative affect about appearance, (2) HIV health-related outcomes and stigma, (3) eating and exercise confusion, and (4) ART non-adherence. The subfactors and total scores revealed bivariate associations with salient health outcomes, including depressive symptoms, HIV sexual transmission risk behaviors, and ART non-adherence. The ABCD and its short form, offer valid means to assess varied aspects of body image disturbance among HIV-infected MSM, and require modest participant burden. C1 [Blashill, Aaron J.; Wilson, Johannes M.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Blashill, Aaron J.; Mayer, Kenneth H.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Blashill, Aaron J.; Baker, Joshua S.; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Blashill, AJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org FU NIAID NIH HHS [P30 AI060354, 5P30 AI060354-08]; NIMH NIH HHS [K23 MH096647, K24MH094214, K24 MH094214, K23MH096647] NR 51 TC 1 Z9 1 U1 2 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JUN PY 2014 VL 18 IS 6 BP 1075 EP 1084 DI 10.1007/s10461-013-0620-z PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA AH5YF UT WOS:000336206400011 PM 24057934 ER PT J AU Mordes, DA Lynch, K Campbell, S Dias-Santagata, D Nose, V Louis, DN Hoang, MP AF Mordes, Daniel A. Lynch, Kerry Campbell, Sharon Dias-Santagata, Dora Nose, Vania Louis, David N. Hoang, Mai P. TI VE1 Antibody Immunoreactivity in Normal Anterior Pituitary and Adrenal Cortex Without Detectable BRAF V600E Mutations SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE VE1; BRAF V600E; Immunohistochemistry; Pituitary gland; Adrenal gland ID IMMUNOHISTOCHEMISTRY; CANCER; CARCINOMA; ADENOMAS; MELANOMA; TUMORS AB Objectives: The VE1 monoclonal antibody was developed to recognize the V600E mutation in BRAF, which is found in various tumors. Methods: We report that the VE1 antibody stains normal anterior pituitary gland and adrenal cortex, which lack detectable BRAF V600E mutations. Results: Staining with the VE1 antibody was seen in the adenohypophysis and correlated well with adrenocorticotropic hormone (ACTH) positive cells. ACTH-positive cells were typically most concentrated in the central mucoid wedge and pars intermedia, and VE1 staining was strong in these regions. Moreover, VE1 staining was seen in ACTH-expressing pituitary adenomas without detectable BRAF mutations. VE1 staining of the adrenal cortex was also significant, with the strongest staining seen in the inner segment of the zona fasciculata. Parathyroid glands, pancreatic islets, or parafollicular C cells in the thyroid showed no VE1 staining. Conclusions: Overall, VE1 staining of endocrine tissues strongly suggests limitations on the use of this antibody for the detection of BRAF mutations. C1 [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hoang, MP (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 820, Boston, MA 02114 USA. EM mhoang@mgh.harvard.edu NR 19 TC 10 Z9 10 U1 1 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 JUN PY 2014 VL 141 IS 6 BP 811 EP 815 DI 10.1309/AJCP37TLZLTUAOJL PG 5 WC Pathology SC Pathology GA AH6KM UT WOS:000336239800009 PM 24838325 ER PT J AU Katz, IR AF Katz, Ira R. TI Mental Health Needs of Older Veterans SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Editorial Material ID NATIONAL-HEALTH; RESILIENCE C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Katz, IR (reprint author), Philadelphia VA Med Ctr, Univ & Woodland Aves, Philadelphia, PA 19104 USA. EM Ira.Katz2@va.gov NR 13 TC 1 Z9 1 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2014 VL 22 IS 6 BP 527 EP 530 DI 10.1016/j.jagp.2014.01.014 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AH4HG UT WOS:000336087400001 PM 24821286 ER PT J AU Garrido, MM Penrod, JD Prigerson, HG AF Garrido, Melissa M. Penrod, Joan D. Prigerson, Holly G. TI Unmet Need for Mental Health Care Among Veterans Receiving Palliative Care: Assessment is Not Enough SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Veterans; psychotherapy; access to care; anxiety; depression; palliative care ID ADVANCED CANCER AB Objective: To determine whether inpatient palliative care teams' assessments of psychological distress affect receipt of in-hospital mental health care (psychotherapy, psychological support, and health and behavior interventions) for seriously ill veterans. Methods: Retrospective review of medical records from 287 seriously ill veterans who received inpatient palliative care consults between 2008 and 2010 in the NY/NJ Veterans Healthcare Network. Results: Of the veterans who were cognitively or physically able to answer questions on the Condensed Memorial Symptom Assessment Scale, 44% reported psychological distress. Of those with distress, 38% accessed mental health care. In logistic regression models adjusted for sociodemographic and health characteristics, there was no evidence that psychological distress reported during the palliative care consult was associated with subsequent mental health care receipt from any type of provider. Conclusions: Efforts to increase mental health care to psychologically distressed palliative care patients need to convert assessments into receipt of needed care. C1 [Garrido, Melissa M.; Penrod, Joan D.] James J Peters VAMC, Bronx, NY 10468 USA. [Garrido, Melissa M.; Penrod, Joan D.] Icahn Sch Med Mt Sinai, New York, NY USA. [Prigerson, Holly G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Prigerson, Holly G.] Harvard Univ, Sch Med, Boston, MA USA. RP Garrido, MM (reprint author), James J Peters VAMC, GRECC, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM melissa.garrido@mssm.edu FU Dept. of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [CDA 11-201/CDP 12-255]; National Palliative Care Research Center; National Cancer Institute [CA106370, CA156732]; Atlantic Philanthropies Health & Aging Policy Fellowship; National Institute of Mental Health [MH63892] FX The following are the funding sources for this research. MMG: Dept. of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (CDA 11-201/CDP 12-255); National Palliative Care Research Center. JDP: The Atlantic Philanthropies Health & Aging Policy Fellowship. HGP: National Institute of Mental Health (MH63892) and National Cancer Institute (CA106370; CA156732). NR 14 TC 5 Z9 5 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2014 VL 22 IS 6 BP 540 EP 544 DI 10.1016/j.jagp.2013.08.008 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AH4HG UT WOS:000336087400003 PM 24119857 ER PT J AU Yeager, DE Magruder, KM AF Yeager, Derik E. Magruder, Kathryn M. TI PTSD Checklist Scoring Rules for Elderly Veterans Affairs Outpatients SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE PTSD; screening; elderly ID POSTTRAUMATIC-STRESS-DISORDER; PREVALENCE AB Objective: To assess the diagnostic performance of the PTSDChecklist (PCL) for three age groups (<50, 50-64, and >= 65 years). Methods: The PCL was compared with the Clinician Administered PTSD Scale, a gold standard for the diagnosis of post-traumatic stress disorder. Receiver operating characteristic curves and the corresponding area under the receiver operating characteristic curve (AUC) and measures of sensitivity and specificity were used to assess the performance of and to determine optimal cutscores for the PCL across the three groups. Analyses were based on 858 randomly selected primary care patients who participated in a study conducted at four Veterans Administration medical centers. Results: AUCs were high for all three age groups (87.55%-88.26%), and there were no significant differences in AUCs across age groups chi(2). Optimal cutscores, however, varied considerably: 24 for the oldest group, 34 for the middle group, and 43 for the youngest group. Conclusion: Recommend use of lower PCL cutscore for older Veterans Administration primary care patients. C1 [Yeager, Derik E.; Magruder, Kathryn M.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Yeager, Derik E.; Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Yeager, DE (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA. EM yeagerde@musc.edu FU Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development; Health Services Research and Development [VCR 99-010-2]; National Center for Research Resources [UL1TR000062] FX Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and Health Services Research and Development (VCR 99-010-2). The views expressed in this report are those of the authors and do not necessarily reflect the position or policy of the Department of Veteran Affairs or the U.S. government.; Also supported by award number UL1TR000062 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 13 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 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2014 VL 22 IS 6 BP 545 EP 550 DI 10.1016/j.jagp.2013.03.009 PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AH4HG UT WOS:000336087400004 PM 24041524 ER PT J AU Covinsky, KE Cenzer, IS Yaffe, K O'Brien, S Blazer, DG AF Covinsky, Kenneth E. Cenzer, Irena Stijacic Yaffe, Kristine O'Brien, Sarah Blazer, Dan G. TI Dysphoria and Anhedonia as Risk Factors for Disability or Death in Older Persons: Implications for the Assessment of Geriatric Depression SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Depression; anhedonia; activities of daily living; quality of life; health status ID SUBTHRESHOLD DEPRESSION; FUNCTIONAL LIMITATIONS; VASCULAR DEPRESSION; COMMUNITY SAMPLE; ELDERLY PERSONS; LATER-LIFE; SYMPTOMS; ADULTS; MORTALITY; DIRECTIONS AB Objectives: Either dysphoria (sadness) or anhedonia (loss of interest in usually pleasurable activities) is required for a diagnosis of major depression. Although major depression is a known risk factor for disability in older persons, few studies have examined the relationship between the two core symptoms of major depression and disability or mortality. Our objective was to examine the relationship between these two core symptoms and time to disability or death. Methods: In a longitudinal cohort study, we used the nationally representative Health and Retirement Study to examine this relationship in 11,353 persons older than 62 years (mean: 73 years) followed for up to 13 years. Dysphoria and anhedonia were assessed with the Short Form Composite International Diagnostic Interview. Our outcome measure was time to either death or increased disability, defined as the new need for help in a basic activity of daily living. We adjusted for a validated disability risk index and other confounders. Results: Compared with subjects without either dysphoria or anhedonia, the risk for disability or death was not elevated in elders with dysphoria without anhedonia (adjusted hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 0.91-1.36). The risk was elevated in those with anhedonia without dysphoria (HR: 1.30; 95% CI: 1.06-1.60) and those with both anhedonia and dysphoria (HR: 1.28; 95% CI: 1.13-1.46). Conclusion: Our results highlight the need for clinicians to learn whether patients have lost interest in usually pleasurable activities, even if they deny sadness. C1 [Covinsky, Kenneth E.; Cenzer, Irena Stijacic; O'Brien, Sarah] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Covinsky, Kenneth E.; Cenzer, Irena Stijacic; Yaffe, Kristine; O'Brien, Sarah] San Francisco VA Med Ctr, San Francisco, CA USA. [Blazer, Dan G.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. RP Covinsky, KE (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr 181G, 4150 Clement, San Francisco, CA 94121 USA. EM ken.covinsky@ucsf.edu FU National Institute on Aging [R01AG028481, K24AG029812] FX Supported by grants R01AG028481 and K24AG029812 from the National Institute on Aging. The Health and Retirement Study is funded by the National Institute on Aging. NR 34 TC 9 Z9 9 U1 5 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2014 VL 22 IS 6 BP 606 EP 613 DI 10.1016/j.jagp.2012.12.001 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AH4HG UT WOS:000336087400011 PM 23602308 ER PT J AU Merker, VL Bredella, MA Cai, W Kassarjian, A Harris, GJ Muzikansky, A Nguyen, R Mautner, VF Plotkin, SR AF Merker, Vanessa L. Bredella, Miriam A. Cai, Wenli Kassarjian, Ara Harris, Gordon J. Muzikansky, Alona Nguyen, Rosa Mautner, Victor F. Plotkin, Scott R. TI Relationship between whole-body tumor burden, clinical phenotype, and quality of life in patients with neurofibromatosis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE neurofibromatosis 1; neurofibromatosis 2; schwannomatosis; quality of life; pain; nerve sheath tumor; whole-body MRI; SF-36 ID DIAGNOSTIC-CRITERIA; TYPE-1; SCHWANNOMATOSIS; CHILDREN; IMPACT AB Patients with neurofibromatosis 1 (NF1), NF2, and schwannomatosis share a predisposition to develop multiple nerve sheath tumors. Previous studies have demonstrated that patients with NF1 and NF2 have reduced quality of life (QOL), but no studies have examined the relationship between whole-body tumor burden and QOL in these patients. We administered a QOL questionnaire (the SF-36) and a visual analog pain scale (VAS) to a previously described cohort of adult neurofibromatosis patients undergoing whole-body MRI. One-sample t-tests were used to compare norm-based SF-36 scores to weighted population means. Spearman correlation coefficients and multiple linear regression analyses controlling for demographic and disease-specific clinical variable were used to relate whole-body tumor volume to QOL scales. Two hundred forty-five patients (142 NF1, 53 NF2, 50 schwannomatosis) completed the study. Subjects showed deficits in selected subscales of the SF-36 compared to adjusted general population means. In bivariate analysis, increased tumor volume was significantly associated with pain in schwannomatosis patients, as measured by the SF-36 bodily pain subscale (rho = -0.287, P = 0.04) and VAS (rho = 0.34, P = 0.02). Regression models for NF2 patients showed a positive relationship between tumor burden and increased pain, as measured by the SF-36 (P = 0.008). Patients with NF1, NF2, and schwannomatosis suffer from reduced QOL, although only pain shows a clear relationship to patient's overall tumor burden. These findings suggest that internal tumor volume is not a primary contributor to QOL and emphasize the need for comprehensive treatment approaches that go beyond tumor-focused therapies such as surgery by including psychosocial interventions. (c) 2014 Wiley Periodicals, Inc. C1 [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Merker, Vanessa L.; Plotkin, Scott R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Bredella, Miriam A.; Cai, Wenli; Harris, Gordon J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kassarjian, Ara] Corades SL, Dept Radiol, Majadahonda, Spain. [Muzikansky, Alona] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Nguyen, Rosa] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. [Nguyen, Rosa; Mautner, Victor F.] Univ Hamburg Hosp, Dept Neurol, Hamburg, Germany. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org OI Merker, Vanessa/0000-0002-4542-5227 FU Department of Defense Neurofibromatosis Research Program [NF050202] FX Grant sponsor: Department of Defense Neurofibromatosis Research Program; Grant number: NF050202. NR 22 TC 15 Z9 15 U1 4 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN PY 2014 VL 164 IS 6 BP 1431 EP 1437 DI 10.1002/ajmg.a.36466 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA AH2BV UT WOS:000335926600010 PM 24664633 ER PT J AU Wakeman, SE Green, TC Rich, JD AF Wakeman, Sarah E. Green, Traci C. Rich, Josiah D. TI From Documenting Death to Comprehensive Care: Applying Lessons from the HIV/AIDS Epidemic to Addiction SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID EXCEPTIONALISM; AIDS C1 [Wakeman, Sarah E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wakeman, Sarah E.] Massachusetts Gen Hosp, Ctr Community Hlth Improvement, Boston, MA 02114 USA. [Wakeman, Sarah E.] Harvard Univ, Sch Med, Boston, MA USA. [Wakeman, Sarah E.; Green, Traci C.; Rich, Josiah D.] Ctr Prisoner Hlth & Human Rights, Providence, RI USA. [Green, Traci C.; Rich, Josiah D.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Green, Traci C.] Rhode Isl Hosp, Dept Emergency Med & Epidemiol, Providence, RI USA. [Rich, Josiah D.] Miriam Hosp, Div Infect Dis, Providence, RI 02906 USA. RP Wakeman, SE (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU NCIPC CDC HHS [U01 CE002165, 5 R21 CE002165-02]; NIAID NIH HHS [P30 AI042853, P30-AI42853]; NIDA NIH HHS [K24 DA022112, K24DA022112] NR 5 TC 2 Z9 2 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 JUN PY 2014 VL 127 IS 6 BP 465 EP 466 DI 10.1016/j.amjmed.2013.12.018 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AH8GD UT WOS:000336374100014 PM 24412918 ER PT J AU Venkatesh, KK Cu-Uvin, S AF Venkatesh, Kartik K. Cu-Uvin, Susan TI Anatomic and Hormonal Changes in the Female Reproductive Tract Immune Environment during the Life Cycle: Implications for HIV/STI Prevention Research SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Review DE Anatomy; female genital tract; HIV; hormones; STI; women ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED INFECTIONS; UTERINE EPITHELIAL-CELLS; HUMAN VAGINAL EPITHELIUM; MENSTRUAL-CYCLE; CERVICAL ECTOPY; POSTMENOPAUSAL WOMEN; HIV-1 TRANSMISSION; MUCOSAL IMMUNITY; INNATE IMMUNITY AB The female genital tract undergoes anatomic changes from birth through menopause. Concurrently, the relative levels and roles of estradiol and progesterone dramatically change during the female life cycle. This review provides a conceptual overview of clinically relevant anatomic and hormonal changes in the female genital tract, and how these changes may affect HIV-1 pathogenesis, transmission, and mucosal immunology and protection against HIV and STIs across the female life cycle. C1 [Venkatesh, Kartik K.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02415 USA. [Venkatesh, Kartik K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cu-Uvin, Susan] Brown Univ, Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02912 USA. [Cu-Uvin, Susan] Brown Univ, Alpert Med Sch, Dept Med, Div Infect Dis, Providence, RI 02912 USA. RP Venkatesh, KK (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02415 USA. EM kvenkatesh@partners.org NR 69 TC 2 Z9 2 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 EI 1600-0897 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD JUN PY 2014 VL 71 IS 6 SI SI BP 495 EP 504 DI 10.1111/aji.12247 PG 10 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA AH1YK UT WOS:000335917600003 PM 24832617 ER PT J AU Miller, RG Brooks, BR Swain-Eng, RJ Basner, RC Carter, GT Casey, P Cohen, AB Dubinsky, R Forshew, D Jackson, CE Kasarskis, E Procaccini, NJ Sanjak, M Tolin, FP AF Miller, Robert G. Brooks, Benjamin Rix Swain-Eng, Rebecca J. Basner, Robert C. Carter, Gregory T. Casey, Patricia Cohen, Adam B. Dubinsky, Richard Forshew, Dallas Jackson, Carlayne E. Kasarskis, Ed Procaccini, Nicholas J. Sanjak, Mohammed Tolin, Fredrik P. TI Quality improvement in neurology: Amyotrophic Lateral Sclerosis Quality Measures SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Editorial Material ID PRACTICE PARAMETER UPDATE; AMERICAN ACADEMY; STANDARDS SUBCOMMITTEE; REPORTING SUBCOMMITTEE; MULTIDISCIPLINARY CARE; OF-LIFE; MANAGEMENT; PATIENT; ALS; SURVIVAL C1 [Miller, Robert G.; Forshew, Dallas] Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA 94114 USA. [Brooks, Benjamin Rix] Univ N Carolina, Carolinas HealthCare Syst, Carolinas Med Ctr, Carolinas Neuromuscular ALS MDA Ctr,Dept Neurol, Charlotte, NC 28223 USA. [Swain-Eng, Rebecca J.] Amer Acad Neurol, Minneapolis, MN USA. [Basner, Robert C.] Columbia Univ, Coll Phys & Surg, Div Pulm Med, New York, NY USA. [Carter, Gregory T.] St Lukes Rehabil Inst, Spokane, WA USA. [Casey, Patricia] Northwestern Med Fac Fdn, Dept Neurol, Chicago, IL USA. [Cohen, Adam B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Dubinsky, Richard] Univ Kansas, Dept Neurol, Kansas City, KS USA. [Jackson, Carlayne E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. [Kasarskis, Ed] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. [Procaccini, Nicholas J.] Swedish Med Ctr, Seattle, WA USA. [Procaccini, Nicholas J.] Univ Washington, Seattle, WA 98195 USA. [Sanjak, Mohammed] Univ N Carolina, Carolinas HealthCare Syst, Carolinas Med Ctr, Carolinas Neuromuscular ALS MDA Ctr,Dept Kinesiol, Charlotte, NC 28223 USA. [Tolin, Fredrik P.] Humana, Chicago, IL USA. RP Miller, RG (reprint author), Calif Pacific Med Ctr, Forbes Norris MDA ALS Res Ctr, San Francisco, CA 94114 USA. EM quality@aan.com NR 30 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 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD JUN PY 2014 VL 15 IS 3-4 BP 165 EP 168 DI 10.3109/21678421.2013.875706 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA AH8KH UT WOS:000336386200003 PM 24707820 ER PT J AU Bruijn, L Cudkowicz, M AF Bruijn, Lucie Cudkowicz, Merit CA Als Clinical Trials Working Grp TI Opportunities for improving therapy development in ALS SO AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION LA English DT Review DE Amyotrophic lateral sclerosis; clinical trials; biomarkers; therapy ID AMYOTROPHIC-LATERAL-SCLEROSIS; RANDOMIZED SEQUENTIAL TRIAL; PHASE-III; MULTICENTER; SURVIVAL; LITHIUM; DESIGNS AB In May 2013, The ALS Association and The Northeast ALS Consortium (NEALS) convened a meeting of stakeholders for a round-table discussion of ways to improve therapy development in ALS. The following overview summarizes issues raised and potential new directions discussed at the meeting. We recommend that future phase II clinical trials in ALS proceed when the proposed treatment is directed at targets that are likely to be involved in ALS pathogenesis in a defined subgroup of patients, and be accompanied by one or more biomarkers to track both clinical progression and pharmacodynamic engagement of the target. Innovations in trial structure and design, and greater involvement of patient advocates, may also improve trials. C1 [Bruijn, Lucie] ALS Assoc, Washington, DC 20005 USA. [Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Res Inst, Boston, MA 02114 USA. RP Bruijn, L (reprint author), ALS Assoc, 125 K St,Suite 250, Washington, DC 20005 USA. EM lucie@alsa-national.org OI Macklin, Eric/0000-0003-1618-3502 NR 15 TC 8 Z9 8 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8421 EI 2167-9223 J9 AMYOTROPH LAT SCL FR JI Amyotroph. Lateral Scher. Frontotemp. Degenerat. PD JUN PY 2014 VL 15 IS 3-4 BP 169 EP 173 DI 10.3109/21678421.2013.872662 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA AH8KH UT WOS:000336386200004 PM 24472060 ER PT J AU Cote, CJ Posner, KL Domino, KB AF Cote, Charles J. Posner, Karen L. Domino, Karen B. TI Death or Neurologic Injury after Tonsillectomy in Children with a Focus on Obstructive Sleep Apnea: Houston, We Have a Problem! SO ANESTHESIA AND ANALGESIA LA English DT Article ID RESPIRATORY COMPLICATIONS; RECURRENT HYPOXEMIA; MALPRACTICE CLAIMS; OPIOID RECEPTOR; RISK-FACTORS; ADENOTONSILLECTOMY; CODEINE; OBESITY; METABOLIZERS; MANAGEMENT AB BACKGROUND: Obesity is epidemic in the United States and With it comes an increased incidence of obstructive sleep apnea (OSA). Evidence regarding opioid sensitivity, as well as recent descriptions of deaths after tonsillectomy prompted a survey of all members of the Society for Pediatric Anesthesia regarding adverse events in children undergoing tonsillectomy. METHODS: An electronic survey was sent to 2377 members of the Society for Pediatric Anesthesia. Additionally, data from the American Society of Anesthesiologists Closed Claims Project were obtained. Adverse events during or after tonsillectomy with or without adenoidectomy in children were included. Children at risk for OSA were identified as either having a positive history for OSA or a post hoc application of the American Society of Anesthesiologists OSA practice guidelines. These children were compared with all other children by Fisher exact test for proportions and t test for continuous variables. RESULTS: A total of 129 cases were identified from the 731 replies to the survey, with 92 meeting inclusion criteria for having adequate data. Another 19 cases with adequate data were identified from the 45 from the American Society of Anesthesiologists Closed Claims Project. A total of 111 cases were included in the final analysis. Death and permanent neurologic injury occurred in 86 (77%) cases and were reported in the operating room, postanesthesia care unit, on the ward, and at home. Sixty-three (57%) children fulfilled American Society of Anesthesiologists criteria to be at risk for OSA. Children categorized as at risk for OSA. were more likely than other children to be obese and to have comorbidities (P < 0.0001). A larger proportion of at risk children had the event attributed to apnea (P = 0.016), whereas all others had a larger proportion of events attributed to hemorrhage (P = 0.006). CONCLUSIONS: Deaths or neurologic injury after tonsillectomy due to apparent apnea in children suggest that at least 16 children could have been rescued had respiratory monitoring been continued throughout first- and second-stage recovery, as well as on the ward during the first postoperative night. A validated pediatric-specific risk assessment scoring system is needed to assist with identifying children at risk for OSA who are not appropriate to be cared for on an outpatient basis. C1 [Cote, Charles J.] Harvard Univ, Sch Med, MassGen Hosp Children, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Posner, Karen L.; Domino, Karen B.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Cote, CJ (reprint author), MassGen Hosp Children, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM cjcote@partners.org FU American Society of Anesthesiologists (ASA), Park Ridge, IL FX Funding: Supported in part by the American Society of Anesthesiologists (ASA), Park Ridge, IL. All opinions expressed are those of the authors and do not reflect the policy of the ASA. NR 41 TC 35 Z9 35 U1 0 U2 8 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 JUN PY 2014 VL 118 IS 6 BP 1276 EP 1283 DI 10.1213/ANE.0b013e318294fc47 PG 8 WC Anesthesiology SC Anesthesiology GA AH7YZ UT WOS:000336352600018 PM 23842193 ER PT J AU Ting, CK Johnson, KB Teng, WN Synoid, ND LaPierre, C Yu, L Westenskow, DR AF Ting, Chien-Kun Johnson, Ken B. Teng, Wei-Nung Synoid, Noah D. LaPierre, Cris Yu, Lu Westenskow, Dwayne R. TI Response Surface Model Predictions of Wake-Up Time During Scoliosis Surgery SO ANESTHESIA AND ANALGESIA LA English DT Article ID ALVEOLAR ANESTHETIC CONCENTRATION; PROPOFOL-REMIFENTANIL ANESTHESIA; SEVOFLURANE REQUIREMENTS; INHALATION ANESTHESIA; CONCENTRATION-AWAKE; CONTROLLED INFUSION; SYSTEM MODEL; FENTANYL; MAC; DESFLURANE AB BACKGROUND: With the use of previously published data, new sevoflurane remifentanil interaction models of various degrees of sedation were created and adapted to desflurane-fentanyl by using minimal alveolar concentration and opioid equivalencies. These models were used to predict return of responsiveness in patients undergoing scoliosis surgery during a wake-up test. Our hypothesis was that one of the interaction models would accurately predict return of responsiveness during a wake-up test. METHODS: Three new sevoflurane remifentanil interaction models were constructed from previous observations in volunteers by using the Observer's Assessment of Alertness/Sedation (OAA/S) scores. These models included predictions of OAA/S<2 (unresponsive), OAA/S<3, and OAA/S<4 (sedation). Twenty-three patients scheduled for scoliosis surgery received a fentanyl desflurane anesthetic. With the use of published pharmacokinetic models, predictions of fentanyl and desflurane effect-site concentrations were recorded throughout surgery and converted to equivalent remifentanil and sevoflurane effect-site concentrations. Data were recorded every 10 seconds from the time when desflurane was turned off until 10 minutes after the patients responded by moving their hands and toes. Model predictions were compared with observations with graphical and temporal analyses. RESULTS: The average difference between the time when a patient first responded and the time when the model predicted that there was a 50% probability that the patient would respond were -2.6 +/- 3.6 minutes (mean +/- SD) for the OAA/S<2 model, 2.8 +/- 5.6 minutes for the OAA/S<3 model and 52.6 +/- 32.3 minutes for the OAA/S<4 model. CONCLUSIONS: The results confirmed our study hypothesis; a sevoflurane remifentanil interaction model built from observations in volunteers and adapted to desflurane and fentanyl accurately predicted patient response during a wake-up test. These results were similar to our previous study comparing model predictions and patient observations after a sevoflurane-remifentanil/fentanyl anesthetic. The OAA/S <2 model most accurately predicted the time patients would respond by moving their fingers and toes. This model may help anesthesiologists better predict return of responsiveness during a wake-up test in patients undergoing spine surgery. C1 [Ting, Chien-Kun; Teng, Wei-Nung] Taipei Vet Gen Hosp, Dept Anesthesiol, Taipei, Taiwan. [Ting, Chien-Kun; Teng, Wei-Nung] Natl Yang Ming Univ, Taipei 112, Taiwan. [Johnson, Ken B.; Synoid, Noah D.; Westenskow, Dwayne R.] Univ Utah, Sch Med, Dept Anesthesiol, Salt Lake City, UT USA. [Johnson, Ken B.; Westenskow, Dwayne R.] Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. [LaPierre, Cris] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [LaPierre, Cris] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Yu, Lu] China Med Univ, Dept Biomed Engn, Coll Basic Med Sci, Shenyang, Liaoning, Peoples R China. RP Ting, CK (reprint author), Taipei Vet Gen Hosp, Dept Anesthesiol, 201,Sect 2,Shi Pai Rd, Taipei, Taiwan. EM ckting2@gmail.com RI Ting, Chien-Kun/C-1389-2012 OI Ting, Chien-Kun/0000-0002-3156-8139 NR 40 TC 0 Z9 0 U1 1 U2 2 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 JUN PY 2014 VL 118 IS 6 BP 1396 EP 1403 DI 10.1213/ANE.0000000000000094 PG 8 WC Anesthesiology SC Anesthesiology GA AH7YZ UT WOS:000336352600040 ER PT J AU Kim, J Won, JS Singh, AK Sharma, AK Singh, I AF Kim, Jinsu Won, Je-Seong Singh, Avtar K. Sharma, Anand K. Singh, Inderjit TI STAT3 Regulation by S-Nitrosylation: Implication for Inflammatory Disease SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; MEDIATED RECEPTOR-BINDING; EPIDERMAL-GROWTH-FACTOR; BRAIN MICROGLIAL CELLS; NITRIC-OXIDE; JAK-STAT; TYROSINE PHOSPHORYLATION; SERINE PHOSPHORYLATION; NITROSO-GLUTATHIONE AB Aims: S-nitrosylation and S-glutathionylation, redox-based modifications of protein thiols, are recently emerging as important signaling mechanisms. In this study, we assessed S-nitrosylation-based regulation of Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway that plays critical roles in immune/inflammatory responses and tumorigenesis. Results: Our studies show that STAT3 in stimulated microglia underwent two distinct redox-dependent modifications, S-nitrosylation and S-glutathionylation. STAT3 S-nitrosylation was associated with inducible nitric oxide synthase (iNOS)-produced nitric oxide (NO) and S-nitrosoglutathione (GSNO), whereas S-glutathionylation of STAT3 was associated with cellular oxidative stress. NO produced by iNOS or treatment of microglia with exogenous GSNO inhibited STAT3 activation via inhibiting STAT3 phosphorylation (Tyr(705)). Consequently, the interleukin-6 (IL-6)-induced microglial proliferation and associated gene expressions were also reduced. In cell-free kinase assay using purified JAK2 and STAT3, STAT3 phosphorylation was inhibited by its selective preincubation with GSNO, but not by preincubation of JAK2 with GSNO, indicating that GSNO-mediated mechanisms inhibit STAT3 phosphorylation through S-nitrosylation of STAT3 rather than JAK2. In this study, we identified that Cys(259) was the target Cys residue of GSNO-mediated S-nitrosylation of STAT3. The replacement of Cys(259) residue with Ala abolished the inhibitory role of GSNO in IL-6-induced STAT3 phosphorylation and transactivation, suggesting the role of Cys(259) S-nitrosylation in STAT3 phosphorylation. Innovation: Microglial proliferation is regulated by NO via S-nitrosylation of STAT3 (Cys(259)) and inhibition of STAT3 (Tyr(705)) phosphorylation. Conclusion: Our results indicate the regulation of STAT3 by NO-based post-translational modification (S-nitrosylation). These findings have important implications for the development of new therapeutics targeting STAT3 for treating diseases associated with inflammatory/immune responses and abnormal cell proliferation, including cancer. Antioxid. Redox Signal. 20, 2514-2527. C1 [Kim, Jinsu; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Won, Je-Seong; Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson Vet Adm Med Ctr, Pathol & Lab Med Serv, Charleston, SC USA. [Sharma, Anand K.; Singh, Inderjit] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 173 Ashley Ave CRI 516, Charleston, SC 29425 USA. EM singhi@musc.edu FU NIH; VA [NS072511, BX001062, NS037766, BX001072] FX This work was supported by grants from NIH and VA (NS072511, BX001062, NS037766 and BX001072). We also acknowledge Ms. Joyce Bryan and Ms. Chara Williams for their help in procurement of animals and supplies. NR 60 TC 13 Z9 13 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN 1 PY 2014 VL 20 IS 16 BP 2514 EP 2527 DI 10.1089/ars.2013.5223 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA AG9SM UT WOS:000335760000003 PM 24063605 ER PT J AU Ballen, KK AF Ballen, Karen K. TI The Optimal Donor Source for Acute Myeloid Leukemia: Do We Know the Answer? SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID HEMATOPOIETIC-CELL TRANSPLANTATION; UMBILICAL-CORD BLOOD; UNRELATED DONOR; GRAFT SOURCE C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Zero Emerson,Suite 118, Boston, MA 02115 USA. EM kballen@partners.org NR 9 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2014 VL 20 IS 6 BP 749 EP 749 DI 10.1016/j.bbmt.2014.04.002 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AH8WH UT WOS:000336418400001 PM 24727331 ER PT J AU Wood, WA Lee, SJ Brazauskas, R Wang, ZW Aljurf, MD Ballen, KK Buchbinder, DK Dehn, J Freytes, CO Lazarus, HM LeMaistre, CF Mehta, P Szwajcer, D Joffe, S Majhail, NS AF Wood, William A. Lee, Stephanie J. Brazauskas, Ruta Wang, Zhiwei Aljurf, Mahmoud D. Ballen, Karen K. Buchbinder, David K. Dehn, Jason Freytes, Cesar O. Lazarus, Hillard M. LeMaistre, Charles F. Mehta, Paulette Szwajcer, David Joffe, Steven Majhail, Navneet S. TI Survival Improvements in Adolescents and Young Adults after Myeloablative Allogeneic Transplantation for Acute Lymphoblastic Leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Adolescent and young adults; Hematopoietic cell transplantation; Allogeneic; Survival ID HEMATOPOIETIC-CELL TRANSPLANTATION; UNRELATED DONORS; 1ST REMISSION; OUTCOMES; CHILDREN AB Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children. (C) 2014 American Society for Blood and Marrow Transplantation. C1 [Wood, William A.] Univ N Carolina, Dept Med, Div Hematol & Oncol, Chapel Hill, NC USA. [Lee, Stephanie J.] Univ Washington, Sch Med, Dept Med, Div Med Oncol, Seattle, WA 98195 USA. [Brazauskas, Ruta] Med Coll Wisconsin, Div Biostat, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Wang, Zhiwei] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Aljurf, Mahmoud D.] King Faisal Specialist Hosp Ctr & Res, Dept Oncol, Riyadh, Saudi Arabia. [Ballen, Karen K.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Buchbinder, David K.] Childrens Hosp Orange Cty, Dept Hematol, Orange, CA 92668 USA. [Dehn, Jason] Natl Marrow Donor Program, Minneapolis, MN USA. [Freytes, Cesar O.] South Texas Vet Hlth Care Syst, Hematopoiet Stem Cell Transplant Program, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [LeMaistre, Charles F.] Sarah Cannon, Hematol & Bone Marrow Transplant, Nashville, TN USA. [Mehta, Paulette] Univ Arkansas Med Sci, Dept Hematol & Oncol, Little Rock, AR 72205 USA. [Szwajcer, David] Univ Manitoba, Sect Haematol Oncol, Dept Internal Med, Winnipeg, MB, Canada. [Szwajcer, David] CancerCare Manitoba, Winnipeg, MB, Canada. [Szwajcer, David] Univ Manitoba, Winnipeg, MB, Canada. [Joffe, Steven] Univ Penn, Perelman Sch Med, Dept Med Eth & Hlth Policy, Philadelphia, PA 19104 USA. [Majhail, Navneet S.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Majhail, Navneet S.] Cleveland Clin, Blood & Marrow Transplant Program, Cleveland, OH 44195 USA. RP Majhail, NS (reprint author), Cleveland Clin, Blood & Marrow Transplant Program, 9500 Euclid Ave R35, Cleveland, OH 44195 USA. EM nmajhail@nmdp.org OI Wood, William/0000-0001-7439-2543; Joffe, Steven/0000-0002-0667-7384 FU Public Health Service Grant/Cooperative Agreement from the National Cancer Institute [U24-CA76518]; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Heart, Lung and Blood Institute and National Cancer Institute [5U01HL069294]; Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; Allos, Inc.; Amgen, Inc.; Angioblast FX Financial disclosure: CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases; a Grant/Cooperative Agreement 5U01HL069294 from National Heart, Lung and Blood Institute and National Cancer Institute; a contract HHSH234200637015C with Health Resources and Services Administration; grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos, Inc., Amgen, Inc., and Angioblast; anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Genzyme Corporation; GlaxoSmithKline; HistoGenetics, Inc.; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; RemedyMD; Sanofi; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; Teva Neuroscience, Inc.; THERAKOS, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, or any other agency of the US government. NR 23 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2014 VL 20 IS 6 BP 829 EP 836 DI 10.1016/j.bbmt.2014.02.021 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AH8WH UT WOS:000336418400015 PM 24607554 ER PT J AU Yanik, GA Horowitz, MM Weisdorf, DJ Logan, BR Ho, VT Soiffer, RJ Carter, SL Wu, J Wingard, JR Difronzo, NL Ferrara, JL Giralt, S Madtes, DK Drexler, R White, ES Cooke, KR AF Yanik, Gregory A. Horowitz, Mary M. Weisdorf, Daniel J. Logan, Brent R. Ho, Vincent T. Soiffer, Robert J. Carter, Shelly L. Wu, Juan Wingard, John R. Difronzo, Nancy L. Ferrara, James L. Giralt, Sergio Madtes, David K. Drexler, Rebecca White, Eric S. Cooke, Kenneth R. TI Randomized, Double-Blind, Placebo-Controlled Trial of Soluble Tumor Necrosis Factor Receptor: Enbrel (Etanercept) for the Treatment of Idiopathic Pneumonia Syndrome after Allogeneic Stem Cell Transplantation: Blood and Marrow Transplant Clinical Trials Network Protocol SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Bone marrow transplantation; IPS; TNF; Pneumonia; Pulmonary ID LUNG INJURY; RISK AB Idiopathic pneumonia syndromes (IPS) is a diffuse, noninfectious lung injury that occurs acutely after allogeneic hematopoietic cell transplantation (HCT). JPS-related mortality has been historically high (>50%) despite treatment with systemic corticosteroids and supportive care measures. We have now examined the role of tumor necrosis factor inhibition in a randomized, double-blind, placebo-controlled trial of corticosteroids with etanercept or placebo. Thirty-four subjects (>= 18 years) with IPS after HCT were randomized to receive methylprednisolone (2 mg/kg/day) plus etanercept (0.4 mg/kg twice weekly X 4 weeks; n = 16) or placebo (n = 18). No active infections and a pathogen-negative bronchoscopy were required at study entry. Response (alive, with complete discontinuation of supplemental oxygen support) and overall survival were examined. This study, originally planned to accrue 120 patients, was terminated prematurely due to slow accrual. In the limited number of patients examined, there were no differences in response rates at day 28 of study. Ten of 16 patients (62.5% [95%,confidence interval {CI}, 35.4% to 84.8%]) receiving etanercept and 12 of 18 patients (66.7% [95% CI, 41,0% to 86.7%]) receiving placebo met the day 28 response definition (P = 1.00). The median survival was 170 days (95% CI, 11 to 362) with etanercept versus 64 days (95% CI, 26 to 209) with placebo (P = .51). Among responders, the-median time to discontinuation of supplemental oxygen was 9 days (etanercept) versus 7 days (placebo). Therapy was well tolerated, With 1 toxicity-related death froth infectious pneumonia in the placebo arm. The treatment of IPS with corticosteroids in adult HCT recipients was associated with high early response rates (>60%) compared with historical reports, with poor overall survival. The addition of etanercept did not lead to further increases in response, although the sample size of this truncated trial preclude a definitive conclusion. (C) 2014 Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation. C1 [Yanik, Gregory A.; Ferrara, James L.] Univ Michigan, Blood & Marrow Transplant Program, Med Ctr, Dept Pediat & Internal Med, Ann Arbor, MI 48109 USA. [Horowitz, Mary M.; Logan, Brent R.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Weisdorf, Daniel J.] Univ Minnesota, Dept Internal Med, Blood & Marrow Transplantat Program, Minneapolis, MN USA. [Ho, Vincent T.; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. [Carter, Shelly L.; Wu, Juan] EMMES Corp, Rockville, MD USA. [Wingard, John R.] Univ Florida, Dept Med, Gainesville, FL USA. [Difronzo, Nancy L.] NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. [Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Dept Stem Cell Transplantat, New York, NY 10021 USA. [Madtes, David K.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA. [Madtes, David K.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Drexler, Rebecca] Natl Marrow Donor Program, Minneapolis, MN USA. [Drexler, Rebecca] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [White, Eric S.] Univ Michigan, Med Ctr, Dept Internal Med Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Cooke, Kenneth R.] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Canc Ctr, Baltimore, MD 21205 USA. RP Yanik, GA (reprint author), Univ Michigan, Blood & Marrow Transplant Program, Med Ctr, 5310 Canc Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM gyanik@umich.edu FU National Heart, Lung, and Blood Institute [U10HL069294]; Leukemia and Lymphoma Society; Burroughs Welcome Fund; National Cancer Institute FX Support for this study was provided by grant U10HL069294 from the National Heart, Lung, and Blood Institute and the National Cancer Institute, The Leukemia and Lymphoma Society (to K.R.C.), and the Burroughs Welcome Fund (to K.R.C.). Immunex Corporation, a wholly owned subsidiary of Amgen Inc., provided study drug and central pharmacy support for the trial. NR 17 TC 13 Z9 13 U1 0 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2014 VL 20 IS 6 BP 858 EP 864 DI 10.1016/j.bbmt.2014.02.026 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA AH8WH UT WOS:000336418400019 PM 24607553 ER PT J AU Neuhaus, V Bot, A Guitton, T Ring, D AF Neuhaus, V. Bot, A. Guitton, T. Ring, D. TI Influence of surgeon and patient factors on distal radius fracture treatment SO BRITISH JOURNAL OF SURGERY LA English DT Meeting Abstract CT 101st Annual Congress of the Swiss-Society-of-Surgery CY MAY 21-23, 2014 CL Berne, SWITZERLAND SP Swiss Soc Surg C1 [Neuhaus, V.] Univ Zurich Hosp, Div Trauma Surg, CH-8091 Zurich, Switzerland. [Neuhaus, V.; Bot, A.; Guitton, T.; Ring, D.] Massachusetts Gen Hosp, Div Hand & Upper Extrem, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1323 EI 1365-2168 J9 BRIT J SURG JI Br. J. Surg. PD JUN PY 2014 VL 101 SU 5 BP 12 EP 12 PG 1 WC Surgery SC Surgery GA AH2PM UT WOS:000335963400038 ER PT J AU Pillai, AK Iqbal, SI Liu, RW Rachamreddy, N Kalva, SP AF Pillai, Anil Kumar Iqbal, Shams I. Liu, Raymond W. Rachamreddy, Niranjan Kalva, Sanjeeva P. TI Segmental Arterial Mediolysis SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Segmental arterial mediolysis; Fibromuscular displasia; Vasculopathy ID FOLLOW-UP; FIBROMUSCULAR DYSPLASIA; HEPATIC ARTERIES; EMBOLIZATION; ANEURYSM AB Segmental arterial mediolysis (SAM) is an uncommon, nonatherosclerotic, noninflammatory, large- to medium-sized arteriopathy first described in 1976. It is characterized histologically by vacuolization and lysis of the outer arterial media leading to dissecting aneurysms and vessel rupture presenting clinically with self-limiting abdominal pain or catastrophic hemorrhages in the abdomen. Patients of all ages are affected with a greater incidence at the fifth and sixth decades. There is a slight male predominance. Imaging findings overlap with inflammatory vasculitis, collagen vascular disease, and fibromuscular dysplasia. The presence of segmental dissections involving the celiac, mesenteric, and/or renal arteries is the key distinguishing features of SAM. Inflammatory markers, genetic tests for collagen vascular disorders, and hypercoagulable studies are negative. Anti-inflammatory agents and immunosuppressants are not effective. A mortality rate of 50 % has been attributed to the acute presentation with aneurysmal rupture necessitating urgent surgical or endovascular treatments; in the absence of the acute presentation, SAM is a self-limiting disease and is treated conservatively. There are no established guidelines on medical therapy, although optimal control of blood pressure is considered the main cornerstone of medical therapy. The long-term prognosis is not known. C1 [Pillai, Anil Kumar; Kalva, Sanjeeva P.] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. [Iqbal, Shams I.] Lahey Clin Fdn, Dept Radiol, Burlington, MA USA. [Liu, Raymond W.; Rachamreddy, Niranjan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Pillai, AK (reprint author), Univ Texas SW Med Ctr Dallas, Dept Radiol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM anil.pillai@utsouthwestern.edu; rliu@partners.org NR 25 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 EI 1432-086X J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JUN PY 2014 VL 37 IS 3 BP 604 EP 612 DI 10.1007/s00270-014-0859-4 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AH7RM UT WOS:000336331300005 PM 24554198 ER PT J AU Antman, EM AF Antman, Elliott M. TI Clinical Research and the Development of Medical Therapeutics SO CIRCULATION JOURNAL LA English DT Review DE Atrial fibrillation; Coagulation; Trials ID NONVALVULAR ATRIAL-FIBRILLATION; PLURIPOTENT STEM-CELLS; FACTOR XA INHIBITOR; ORAL ANTICOAGULANTS; NETWORK MEDICINE; WARFARIN; EDOXABAN; THERAPY; METAANALYSIS; DISCOVERY AB Clinical research plays a central role in the development of medical therapeutics, but the current system is estimated to take 10-15 years from initial discovery to regulatory approval, at a cost of approximately US$1 billion. Contrast the paths by which 2 anticoagulant options for atrial fibrillation were discovered and ultimately established as treatment options in clinical medicine. Warfarin was discovered by serendipity and compared with placebo in relatively small trials; this was associated with a low cost of development. The new oral anticoagulants were synthesized to provide highly specific, targeted inhibition of critical steps in the coagulation system. They were compared with warfarin for prevention of stroke and systemic embolic events in large, phase 3 trials; this resulted in very expensive development programs. Neither of these paths is desirable for future development of therapeutics. We need to focus on innovative approaches at the preclinical level (systems approach, greater use of inducible pluripotent stem cells, use of novel bioengineering platforms) and clinical trial level (adaptive design, greater use of new and emerging technology). Focusing on disruptive innovations for development of medical therapeutics has the potential to bring us closer to the goal of precision medicine where safer, more effective treatments are discovered in a more efficient system. C1 [Antman, Elliott M.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Antman, EM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM eantman@rics.bwh.harvard.edu FU Daiichi Sankyo FX Research grant from Daiichi Sankyo to Brigham and Women's Hospital (TIMI Study Group) to conduct a phase 3 trial with edoxaban. NR 28 TC 2 Z9 2 U1 1 U2 4 PU JAPANESE CIRCULATION SOC PI TOYKO PA 18TH FLOOR IMPERIAL HOTEL TOWER, 1-1-1 UCHISAIWAI-CHO CHIYODA-KU, TOYKO, 100-0011, JAPAN SN 1346-9843 EI 1347-4820 J9 CIRC J JI Circ. J. PD JUN PY 2014 VL 78 IS 6 BP 1267 EP 1271 DI 10.1253/circj.CJ-14-0459 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH8HM UT WOS:000336378000001 PM 24837573 ER PT J AU DeAngelo, DJ Chen, L Guerin, A Styles, A Giguere-Duval, P Wu, EQ AF DeAngelo, Daniel J. Chen, Lei Guerin, Annie Styles, Amy Giguere-Duval, Philippe Wu, Eric Q. TI Impact of Timely Switching From Imatinib to a Second-Generation Tyrosine Kinase Inhibitor After 12-Month Complete Cytogenetic Response Failure: A Chart Review Analysis SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Review DE Chart review; Chronic myelogenous leukemia; Dasatinib; Nilotinib; Treatment response ID CHRONIC MYELOID-LEUKEMIA; CYTARABINE; INTERFERON; RESISTANCE AB In patients with chronic myelogenous leukemia in chronic phase (CML-CP), the achievement of a complete cytogenetic response (CCyR) at 1 year is associated with an improved overall survival, therefore, we assessed the outcomes of patients who switched therapy (n = 306) versus those who continued imatinib treatment (n = 287) after failure to achieve CCyR 1 year after imatinib initiation. We found a higher rate of CCyR among patients who switched therapy. Introduction: In this study, cytogenetic response rate after timely switching to a second-generation tyrosine kinase inhibitor (TKI) was evaluated among patients with CML-CP, after failure to achieve CCyR 1 year after imatinib initiation. Patients and Methods: An online physician-administered medical chart review was used to retrospectively collect information from 108 US-based hematologists and oncologists on CML-CP patients who initiated imatinib as first-line therapy and failed to achieve CCyR at 12 months after imatinib initiation. Patients who switched to a second generation TKI within 3 months after the CCyR failure were defined as timely switchers, and those who continued taking imatinib for at least 3 months after the CCyR failure were defined as nonswitchers. CCyR achievement was compared between timely switchers and nonswitchers using multivariate Cox proportional hazard models. Results: Physicians provided information on 593 patients, with 306 defined as timely switchers and 287 defined as nonswitchers. Among the nonswitchers, 78 switched to a second-generation TKI at a later date. After adjusting for potential confounding factors, timely switchers had statistically significantly greater likelihood of achieving CCyR (hazard ratio, 1.80; P =.002) compared with nonswitchers. Conclusion: Timely switching from imatinib to a second-generation TKI after CCyR failure 1 year after imatinib initiation was associated with a greater likelihood of achieving CCyR compared with delaying the switch or not switching to a second-generation TKI. (C) 2014 Elsevier Inc. All rights reserved. C1 [DeAngelo, Daniel J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chen, Lei] Novartis Pharmaceut, E Hanover, NJ USA. [Guerin, Annie; Styles, Amy; Giguere-Duval, Philippe; Wu, Eric Q.] Anal Grp Inc, Montreal, PQ H3B 4W5, Canada. RP Guerin, A (reprint author), Anal Grp Inc, 1000 Rue Gauchetiere Ouest,Bur 1200, Montreal, PQ H3B 4W5, Canada. EM aguerin@analysisgroup.com FU Novartis Pharmaceuticals Corporation FX This research was sponsored by Novartis Pharmaceuticals Corporation, which manufactures imatinib and nilotinib. NR 16 TC 2 Z9 3 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD JUN PY 2014 VL 14 IS 3 BP 245 EP 251 DI 10.1016/j.clml.2013.12.002 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA AH5UC UT WOS:000336195600010 PM 24393622 ER PT J AU Li, LT Hicks, SC Davila, JA Kao, LS Berger, RL Arita, NA Liang, MK AF Li, L. T. Hicks, S. C. Davila, J. A. Kao, L. S. Berger, R. L. Arita, N. A. Liang, M. K. TI Circular closure is associated with the lowest rate of surgical site infection following stoma reversal: a systematic review and multiple treatment meta-analysis SO COLORECTAL DISEASE LA English DT Review DE Ostomy; enterostomy; ileostomy; colostomy; takedown; wound ID HEALTH-CARE INTERVENTIONS; LOOP ILEOSTOMY CLOSURE; ISPOR TASK-FORCE; COLOSTOMY CLOSURE; COLORECTAL SURGERY; WOUND-INFECTION; METHODOLOGICAL QUALITY; CONTROLLED-TRIALS; METAANALYSIS; COMPLICATIONS AB Aim Stoma reversal is frequently complicated by surgical site infection (SSI). To reduce SSI, several techniques for skin closure have been studied, with no agreement on which is best. The aim of this study was to identify the skin closure technique associated with the lowest rate of SSI following stoma reversal. Method We systematically searched MEDLINE (PubMed and OvidSP), Scopus and clinical registries from 1 January 1980 to 24 March 2012, and included original reports on adult patients following stoma reversal. A network of treatments was created to map the comparisons between skin closure techniques, including primary closure, primary closure with a drain, secondary closure, delayed primary closure, loose primary closure and circular closure. Pairwise meta-analyses were performed for all available direct comparisons of closure types and heterogeneity was assessed. A multiple-treatments meta-analysis was conducted to estimate relative treatment effects between competing closure types (reported as an odds ratio with 95% credible interval, and a probability that each treatment is best). Several sensitivity analyses were performed. Results Fifteen studies were identified with a total of 2921 cases of stoma reversal. Overall, study quality was poor with observed low (one study), moderate (seven studies) and high (seven studies) risk of bias. Circular closure was associated with the lowest SSI risk (OR 0.12; 95% CI 0.02-0.40) and was the best of six skin closure techniques (probability of being best = 68.9%). Circular closure remained the best after sensitivity analyses. Conclusion This study showed that circular closure is the best skin closure technique after stoma reversal in terms of SSI rate, but the quality of supporting evidence is limited, precluding definite conclusions. C1 [Li, L. T.; Berger, R. L.; Arita, N. A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Boston, MA USA. [Hicks, S. C.] Dana Farber Canc Inst, Dept Stat, Boston, MA 02115 USA. [Davila, J. A.] Univ Texas Hlth Sci Ctr Houston, Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Houston, TX 77030 USA. [Kao, L. S.; Liang, M. K.] Univ Texas Hlth Sci Ctr Houston, Dept Surg, Houston, TX 77030 USA. RP Li, LT (reprint author), 2450 Holcombe,Suite 01Y, Houston, TX 77021 USA. EM Linday@bcm.edu RI Liang, Mike/L-8493-2015; OI Liang, Mike/0000-0001-7063-7291; Hicks, Stephanie/0000-0002-7858-0231 NR 39 TC 6 Z9 6 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1462-8910 EI 1463-1318 J9 COLORECTAL DIS JI Colorectal Dis. PD JUN PY 2014 VL 16 IS 6 BP 406 EP 416 DI 10.1111/codi.12556 PG 11 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA AH2GW UT WOS:000335940500013 PM 24422861 ER PT J AU Tyler, KL AF Tyler, Kenneth L. TI Current developments in understanding of West Nile virus central nervous system disease SO CURRENT OPINION IN NEUROLOGY LA English DT Review DE acute flaccid paralysis; antiviral therapy; encephalitis; meningitis; vaccine; West Nile virus ID UNITED-STATES; T-CELLS; ANTIVIRAL RESPONSE; FLACCID PARALYSIS; CHIMERIC VACCINE; IMMUNE-RESPONSE; INFECTION; ENCEPHALITIS; PATHOGENESIS; OUTBREAK AB Purpose of reviewWest Nile virus (WNV) is the most important cause of epidemic encephalitis in the United States. We review articles published in the last 18months related to the epidemiology, immunology, clinical features, and treatment of this disease.Recent findingsThere was a resurgence in WNV disease in the United States in 2012. The WNV strain now predominant in the United States (NA/WN02) differs from the initial emergent isolate in 1999 (NY99). However, differences in the genetics of currently circulating United States WNV strains do not explain variations in epidemic magnitude or disease severity. Innate and acquired immunity are critical in control of WNV, and in some cases pathways are central nervous system specific. The clinical features of infection are now well understood, although nonconfirmed observations of chronic viral excretion in urine remain controversial. There is no specific antiviral therapy for WNV, but studies of antivirals specific for other flaviviruses may identify agents with promise against WNV. Phase I and II human WNV vaccine clinical trials have established that well tolerated and immunogenic WNV vaccines can be developed.SummaryWNV remains an important public health problem. Although recent studies have significantly increased our understanding of host immune and genetic factors involved in control of WNV infection, no specific therapy is yet available. Development of a well tolerated, immunogenic, and effective vaccine against WNV is almost certainly feasible, but economic factors and the lack of predictability of the magnitude and location of outbreaks are problematic for designing phase III trials and ultimate licensure. C1 [Tyler, Kenneth L.] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA. [Tyler, Kenneth L.] Eastern Colorado Healthcare Syst, Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Sch Med, Dept Neurol, Mailstop B-182,12700 East 19th Ave, Aurora, CO 80045 USA. EM ken.tyler@ucdenver.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NINDS [1 R01 NS076512]; NIAID [1 R21 AI01064]; Department of Veterans Affairs (MERIT) [BX000963] FX K.L.T. is supported by grants from the NINDS (1 R01 NS076512), NIAID (1 R21 AI01064), and the Department of Veterans Affairs (MERIT Grant BX000963). NR 64 TC 7 Z9 7 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1350-7540 EI 1473-6551 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD JUN PY 2014 VL 27 IS 3 BP 342 EP 348 DI 10.1097/WCO.0000000000000088 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AH2QQ UT WOS:000335966500013 PM 24722324 ER PT J AU Schwartz, KA Preer, G McKeag, H Newton, AW AF Schwartz, Kimberly A. Preer, Genevieve McKeag, Heather Newton, Alice W. TI Child maltreatment: a review of key literature in 2013 SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE abusive head trauma; child maltreatment; child neglect; child physical abuse; child sexual abuse ID ABUSIVE HEAD TRAUMA; HOME-VISITATION; PHYSICAL ABUSE; YOUNG-CHILDREN; UNITED-STATES; SEXUAL-ABUSE; OUTCOMES; UPDATE; HEALTH; CARE AB Purposes of reviewThis review summarizes new findings in the field of maltreatment, addressing epidemiology, physical abuse, abusive head trauma, sexual abuse, sequelae, and prevention.Recent findingsMany articles this year focus on establishing a framework for thinking about how to evaluate a child for maltreatment, the consequences of maltreatment, and the current understanding of prevention efforts. Interestingly, some research has helped to reinforce some concepts that were clinically appreciated, especially related to retinal hemorrhages.SummaryThe volume, quality, and breadth of research relating to child maltreatment continue to improve and expand our understanding of child abuse pediatrics. These authors summarize notable advances in our understanding of child maltreatment over the past year. C1 [Schwartz, Kimberly A.] Boston Med Ctr, Dept Pediat, Child Protect Team, Boston, MA USA. [Preer, Genevieve] Boston Med Ctr, Dept Pediat, Div Family Advocacy, Boston, MA USA. [McKeag, Heather] Tufts Univ, Sch Med, Dept Pediat, Boston, MA 02111 USA. [McKeag, Heather] Tufts Floating Hosp Children, Child Protect Program, Boston, MA USA. [Newton, Alice W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Newton, Alice W.] Massachusetts Gen Hosp, Child Protect Program, Boston, MA 02114 USA. RP Newton, AW (reprint author), Massachusetts Gen Hosp, Dept Pediat, Room 516,175 Cambridge St, Boston, MA 02114 USA. EM anewton@partners.org NR 47 TC 5 Z9 5 U1 5 U2 36 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 EI 1531-698X J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD JUN PY 2014 VL 26 IS 3 BP 396 EP 404 DI 10.1097/MOP.0000000000000102 PG 9 WC Pediatrics SC Pediatrics GA AH2MY UT WOS:000335956800020 PM 24786369 ER PT J AU Miller, PS Evangelista, LS Giger, JN Martinez-Maza, O Corvera-Tindel, T Magpantay, L Pena, G Doering, LV AF Miller, Pamela S. Evangelista, Lorraine S. Giger, Joyce Newman Martinez-Maza, Otoniel Corvera-Tindel, Teresita Magpantay, Larry Pena, Guadalupe Doering, Lynn V. TI Exhaustion, immuno-inflammation, and pathogen burden after cardiac surgery: An exploratory study SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE vital exhaustion; inflammation; pathogen burden; Coronary heart disease; herpesviruses; cytokines ID C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; ANTIINFLAMMATORY CYTOKINE INTERLEUKIN-10; BYPASS GRAFT-SURGERY; VITAL EXHAUSTION; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; SOCIOECONOMIC-STATUS; ADHESION MOLECULES; ANGINA-PECTORIS AB Background: Exhaustion, a consequence of prolonged stress characterized by unusual fatigue, is associated with increased risk of cardiac morbidity and mortality. In patients recovering from coronary artery bypass (CABG), little is known about the relationship of 1) immune-mediated inflammation and resultant endothelial activation, and 2) cumulative exposure to infectious pathogens (pathogen burden (PB)) implicated in coronary atherosclerosis to exhaustion. Aim: The aim of this exploratory study was to investigate the association of PB, inflammatory markers (interleukin (IL)-6, IL-10) and a marker of endothelial activation (soluble intercellular adhesion molecule-1 (sICAM-1)) to exhaustion. Methods: One to two months post-CABG, 42 individuals who met inclusion criteria were assessed for exhaustion using the Maastricht Interview for Vital Exhaustion. Serum IgG antibodies to herpes simplex virus (HSV)-1, HSV-2, cytomegalovirus, Epstein Barr virus, and inflammatory and endothelial activation markers were measured by enzyme-linked immunosorbent assay. Pathogen burden was defined as the total number of seropositive exposures: low (0-1), moderate (2-3), and high (4). Results: Prevalence of exhaustion was 40.5%. Relative to non-exhausted patients, exhausted patients demonstrated a higher frequency of moderate PB (h=0.73, p=0.04) but lower frequency of high PB (h=1.05, p=0.03). Exhaustion showed a non-significant trend for positive correlations with IL-6 and sICAM-1 levels, and inverse relation to PB. In subgroup analysis, exhausted patients had stronger correlations with IL-6 and IL-6:IL-10 and a tendency towards higher serum IL-10 concentrations compared with their non-exhausted counterparts. Conclusion: This hypothesis-generating study provides preliminary evidence that elevated post-CABG exhaustion may be associated with PB, inflammation, and endothelial activation. C1 [Miller, Pamela S.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Miller, Pamela S.; Giger, Joyce Newman; Corvera-Tindel, Teresita; Doering, Lynn V.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Evangelista, Lorraine S.] Univ Calif Irvine, Program Nursing Sci, Irvine, CA USA. [Giger, Joyce Newman] Amer Univ Hlth Sci, Signal Hill, CA USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. [Corvera-Tindel, Teresita] Vet Affairs Greater Los Angeles Hlth Care Syst, Nursing Res Dept, Los Angeles, CA USA. [Magpantay, Larry; Pena, Guadalupe] Univ Calif Los Angeles, David Geffen Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90095 USA. RP Miller, PS (reprint author), Univ Calif San Francisco, Sch Nursing, 2 Koret Way,N411Y,Box 0606, San Francisco, CA 94143 USA. EM Pamela.Miller@ucsf.edu RI Martinez-Maza, Otoniel/B-2667-2009 OI Martinez-Maza, Otoniel/0000-0003-1364-0675 FU American Academy of Nurse Practitioners Foundation; Sigma Theta Tau International; Veterans Affairs Pre-doctoral Nurse Fellowship; James B. Pendleton Charitable Trust; McCarthy Family Foundation FX This work was supported by grants from the American Academy of Nurse Practitioners Foundation; Sigma Theta Tau International; and Veterans Affairs Pre-doctoral Nurse Fellowship. This work was carried out in the facilities of the UCLA AIDS Institute, which were supported, in part, by funds from the James B. Pendleton Charitable Trust and the McCarthy Family Foundation. NR 45 TC 1 Z9 1 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1474-5151 EI 1873-1953 J9 EUR J CARDIOVASC NUR JI Eur. J. Cardiovasc. Nurs. PD JUN PY 2014 VL 13 IS 3 BP 211 EP 220 DI 10.1177/1474515113482805 PG 10 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA AG8RO UT WOS:000335686100003 PM 23524631 ER PT J AU Kitaoka, T Miyoshi, Y Namba, N Miura, K Kubota, T Ohata, Y Fujiwara, M Takagi, M Hasegawa, T Juppner, H Ozono, K AF Kitaoka, Taichi Miyoshi, Yoko Namba, Noriyuki Miura, Kohji Kubota, Takuo Ohata, Yasuhisa Fujiwara, Makoto Takagi, Masaki Hasegawa, Tomonobu Jueppner, Harald Ozono, Keiichi TI Two Japanese familial cases of Caffey disease with and without the common COL1A1 mutation and normal bone density, and review of the literature SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE Cortical bone; Hyperostosis; Type 1 collagen; Mutation; Bone mineral density; Bone formation ID INFANTILE CORTICAL HYPEROSTOSIS; HYPER-OSTOSIS; MR FINDINGS; SPECTRUM AB Caffey disease, also known as infantile cortical hyperostosis, is a rare bone disease characterized by acute inflammation with swelling of soft tissues and hyperostosis of the outer cortical surface in early infancy. The common heterozygous mutation of the COL1A1 gene, p.Arg1014Cys, has been reported in patients with Caffey disease. However, its pathogenesis remains to be elucidated, and the reason for the incomplete penetrance and transient course of the disease is still unclear. In the present study, we performed mutation analysis of the COL1A1 and COL1A2 genes and measured bone mineral density in two Japanese familial cases of Caffey disease. The index case and two clinically healthy members of one family carry the common heterozygous mutation; in contrast, no mutation in COL1A1 or COL1A2 was identified in the affected members of the second family. In addition, we found normal bone mineral density in adult patients of both families who have had an episode of cortical hyperostosis regardless of the presence or absence of the common p.Arg1014Cys mutation. Conclusion: The results reveal that Caffey disease is genetically heterogeneous and that affected and unaffected adult patients with or without the common COL1A1 mutation have normal bone mineral density. C1 [Kitaoka, Taichi; Miyoshi, Yoko; Namba, Noriyuki; Miura, Kohji; Kubota, Takuo; Ohata, Yasuhisa; Fujiwara, Makoto; Ozono, Keiichi] Osaka Univ, Grad Sch Med, Dept Pediat, Suita, Osaka 5650871, Japan. [Takagi, Masaki; Hasegawa, Tomonobu] Keio Univ, Dept Pediat, Sch Med, Shinjuku Ku, Tokyo 1608582, Japan. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Dept Pediat, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Dept Med, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Dept Pediat, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ozono, K (reprint author), Osaka Univ, Grad Sch Med, Dept Pediat, 2-2 Yamada Oka, Suita, Osaka 5650871, Japan. EM keioz@ped.med.osaka-u.ac.jp FU Ministry of Health, Labour, and Welfare of Japan [KH20Q007a-1] FX This study was supported in part by grants-in-aid from the Ministry of Health, Labour, and Welfare (KH20Q007a-1) of Japan. NR 22 TC 2 Z9 2 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6199 EI 1432-1076 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD JUN PY 2014 VL 173 IS 6 BP 799 EP 804 DI 10.1007/s00431-013-2252-8 PG 6 WC Pediatrics SC Pediatrics GA AH8ON UT WOS:000336397500015 PM 24390061 ER PT J AU De Greef, D Aernouts, J Aerts, J Cheng, JT Horwitz, R Rosowski, JJ Dirckx, JJJ AF De Greef, Daniel Aernouts, Jef Aerts, Johan Cheng, Jeffrey Tao Horwitz, Rachelle Rosowski, John J. Dirckx, Joris J. J. TI Viscoelastic properties of the human tympanic membrane studied with stroboscopic holography and finite element modeling SO HEARING RESEARCH LA English DT Article ID HUMAN MIDDLE-EAR; SOUND-TRANSMISSION; MOTION; SURFACE; TOMOGRAPHY; EARDRUM; RABBIT; GERBIL AB A new anatomically-accurate Finite Element (FE) model of the tympanic membrane (TM) and malleus was combined with measurements of the sound-induced motion of the TM surface and the bony manubrium, in an isolated TM-malleus preparation. Using the results, we were able to address two issues related to how sound is coupled to the ossicular chain: (i) Estimate the viscous damping within the tympanic membrane itself, the presence of which may help smooth the broadband response of a potentially highly resonant TM, and (ii) Investigate the function of a peculiar feature of human middle-ear anatomy, the thin mucosal epithelial fold that couples the mid part of the human manubrium to the TM. Sound induced motions of the surface of ex vivo human eardrums and mallei were measured with stroboscopic holography, which yields maps of the amplitude and phase of the displacement of the entire membrane surface at selected frequencies. The results of these measurements were similar, but not identical to measurements made in intact ears. The holography measurements were complemented by laser-Doppler vibrometer measurements of sound-induced umbo velocity, which were made with fine-frequency resolution. Comparisons of these measurements to predictions from a new anatomically accurate FE model with varied membrane characteristics suggest the TM contains viscous elements, which provide relatively low damping, and that the epithelial fold that connects the central section of the human manubrium to the TM only loosely couples the TM to the manubrium. The laser-Doppler measurements in two preparations also suggested the presence of significant variation in the complex modulus of the TM between specimens. (C) 2014 Elsevier B.V. All rights reserved. C1 [De Greef, Daniel; Aernouts, Jef; Aerts, Johan; Dirckx, Joris J. J.] Univ Antwerp, Lab Biomed Phys, B-2020 Antwerp, Belgium. [Aernouts, Jef; Cheng, Jeffrey Tao; Horwitz, Rachelle; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Aernouts, Jef; Cheng, Jeffrey Tao; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Horwitz, Rachelle; Rosowski, John J.] Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Boston, MA 02115 USA. RP De Greef, D (reprint author), Univ Antwerp, Lab Biomed Phys, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. EM daniel.degreef@uantwerpen.be OI De Greef, Daniel/0000-0003-2631-4211 FU agency for Innovation by Science and Technology in Flanders (IWT-Vlaanderen); Research Foundation Flanders (FWO); University of Antwerp; US National Institute of Health FX Financial support to this project was given by the agency for Innovation by Science and Technology in Flanders (IWT-Vlaanderen), the Research Foundation Flanders (FWO), the University of Antwerp and the US National Institute of Health. We thank Mike Ravicz and Saumil Merchant for the valuable discussions, Melissa McKinnon for her technical assistance. NR 35 TC 16 Z9 16 U1 1 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD JUN PY 2014 VL 312 BP 69 EP 80 DI 10.1016/j.heares.2014.03.002 PG 12 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA AH8BD UT WOS:000336358200008 PM 24657621 ER PT J AU Halko, MA Connors, EC Sanchez, J Merabet, LB AF Halko, Mark A. Connors, Erin C. Sanchez, Jaime Merabet, Lotfi B. TI Real World Navigation Independence in the Early Blind Correlates With Differential Brain Activity Associated With Virtual Navigation SO HUMAN BRAIN MAPPING LA English DT Article DE early blind; virtual environments; navigation; way finding; path integration; posterior parietal cortex; temporal parietal junction ID FUNCTIONAL MAGNETIC-RESONANCE; SPATIAL NAVIGATION; CAUDATE-NUCLEUS; PLACE CELLS; ROUTE; ACTIVATION; CORTEX; HIPPOCAMPUS; COMPLEX; ABILITY AB Navigating is a complex cognitive task that places high demands on spatial abilities, particularly in the absence of sight. Significant advances have been made in identifying the neural correlates associated with various aspects of this skill; however, how the brain is able to navigate in the absence of visual experience remains poorly understood. Furthermore, how neural network activity relates to the wide variability in navigational independence and skill in the blind population is also unknown. Using functional magnetic resonance imaging, we investigated the neural correlates of audio-based navigation within a large scale, indoor virtual environment in early profoundly blind participants with differing levels of spatial navigation independence (assessed by the Santa Barbara Sense of Direction scale). Performing path integration tasks in the virtual environment was associated with activation within areas of a core network implicated in navigation. Furthermore, we found a positive relationship between Santa Barbara Sense of Direction scores and activation within right temporal parietal junction during the planning and execution phases of the task. These findings suggest that differential navigational ability in the blind may be related to the utilization of different brain network structures. Further characterization of the factors that influence network activity may have important implications regarding how this skill is taught in the blind community. Hum Brain Mapp 35:2768-2778, 2014. (c) 2013 Wiley Periodicals, Inc. C1 [Halko, Mark A.] Harvard Univ, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol, Beth Israel Deaconess Med Ctr,Med Sch, Boston, MA 02114 USA. [Connors, Erin C.; Merabet, Lotfi B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Lab Visual Neuroplast,Dept Ophthalmol, Boston, MA 02114 USA. [Sanchez, Jaime] Univ Chile, Dept Comp Sci, Santiago, Chile. [Sanchez, Jaime] Univ Chile, CARE, Santiago, Chile. RP Merabet, LB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM lotfi_merabet@meei.harvard.edu OI Halko, Mark/0000-0002-7427-0789 FU NEI NIH HHS [R01 EY019924] NR 57 TC 6 Z9 7 U1 2 U2 12 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 JUN PY 2014 VL 35 IS 6 BP 2768 EP 2778 DI 10.1002/hbm.22365 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AF2PX UT WOS:000334555100021 PM 24027192 ER PT J AU Falkner, B Ingelfinger, J AF Falkner, Bonita Ingelfinger, Julie TI Understanding the Power of Perinatal Events and Metabolic Status in Childhood SO HYPERTENSION LA English DT Editorial Material ID BLOOD-PRESSURE; BIRTH-WEIGHT; DISEASE; GROWTH; RISK; LIFE C1 [Falkner, Bonita] Thomas Jefferson Univ, Dept Med & Pediat, Philadelphia, PA 19107 USA. [Ingelfinger, Julie] Massachusetts Gen Children, MassGen Hosp Children, Pediat Nephrol Unit, Boston, MA USA. RP Falkner, B (reprint author), Thomas Jefferson Univ, Dept Med & Pediat, 833 Chestnut St,Suite 700, Philadelphia, PA 19107 USA. EM bonita.falkner@jefferson.edu NR 11 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUN PY 2014 VL 63 IS 6 BP 1166 EP 1167 DI 10.1161/HYPERTENSIONAHA.114.03290 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AG5XL UT WOS:000335491900148 PM 24688124 ER PT J AU Raz, I Scirica, BM Braunwald, E Mosenzon, O Hirshberg, B Wiviott, SD Frederich, R Davidson, J Leiter, LA Bhatt, DL AF Raz, I Scirica, B. M. Braunwald, E. Mosenzon, O. Hirshberg, B. Wiviott, S. D. Frederich, R. Davidson, J. Leiter, L. A. Bhatt, D. L. TI SAXAGLIPTIN AND CARDIOVASCULAR OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES SO HYPERTENSION LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the High-Blood-Pressure-Research-Council-of-Australia (HBPRCA) / 39th Annual Scientific Meeting of the Australian-Atherosclerosis-Society (AAS) CY DEC 05-07, 2013 CL Melbourne, AUSTRALIA SP High Blood Pressure Res Council Australia, Australian Atherosclerosis Soc C1 [Raz, I; Mosenzon, O.] Hadassah Univ Hosp, Dept Med, Diabet Unit, IL-91240 Jerusalem, Israel. [Scirica, B. M.; Wiviott, S. D.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Scirica, B. M.; Braunwald, E.; Wiviott, S. D.; Bhatt, D. L.] Harvard Univ, Sch Med, Boston, MA USA. [Braunwald, E.; Bhatt, D. L.] VA Boston Healthcare Syst, TIMI Study Grp, Div Cardiovasc, Brigham & Womens Hosp, Boston, MA USA. [Hirshberg, B.] AstraZeneca Res & Dev, Wilmington, DE USA. [Frederich, R.] Bristol Myers Squibb Co, Princeton, NJ USA. [Davidson, J.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Endocrinol, Dallas, TX 75390 USA. [Leiter, L. A.] Univ Toronto, St Michaels Hosp, Div Endocrinol & Metab, Keenan Res Ctr,Li Ka Shing Knowledge Inst, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUN PY 2014 VL 63 IS 6 BP E167 EP E167 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AG5XL UT WOS:000335491900114 ER PT J AU Sullivan, D Raal, F Giugliano, RP Koren, MJ Roth, EM Weiss, R Kim, JB Somaratne, RS Yang, J Liu, T Albizem, M Scott, R Wasserman, SM Stein, EA AF Sullivan, D. Raal, F. Giugliano, R. P. Koren, M. J. Roth, E. M. Weiss, R. Kim, J. B. Somaratne, R. S. Yang, J. Liu, T. Albizem, M. Scott, R. Wasserman, S. M. Stein, E. A. TI EFFICACY AND SAFETY OF AMG 145, A FULLY HUMAN MONOCLONAL ANTIBODY TO PCSK9: DATA FROM FOUR PHASE 2 STUDIES IN OVER 1200 PATIENTS SO HYPERTENSION LA English DT Meeting Abstract CT 35th Annual Scientific Meeting of the High-Blood-Pressure-Research-Council-of-Australia (HBPRCA) / 39th Annual Scientific Meeting of the Australian-Atherosclerosis-Society (AAS) CY DEC 05-07, 2013 CL Melbourne, AUSTRALIA SP High Blood Pressure Res Council Australia, Australian Atherosclerosis Soc C1 [Sullivan, D.] Univ Witwatersrand, Carbohydrate & Lipid Metab Res Unit, Johannesburg, South Africa. [Raal, F.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Giugliano, R. P.] Jacksonville Ctr Clin Res, Jacksonville, FL USA. [Koren, M. J.] Royal Prince Alfred Hosp, Dept Clin Biochem, Camperdown, NSW 2050, Australia. [Roth, E. M.] Sterling Res Grp, Cincinnati, OH USA. [Weiss, R.] Maine Res Associates, Auburn, ME USA. [Kim, J. B.; Somaratne, R. S.; Yang, J.; Liu, T.; Albizem, M.; Scott, R.; Wasserman, S. M.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Stein, E. A.] Metab & Atherosclerosis Res Ctr, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUN PY 2014 VL 63 IS 6 BP E165 EP E166 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AG5XL UT WOS:000335491900108 ER PT J AU Hsiue, PP Gregson, AL Injean, P Vangala, S Brindis, RG Shemin, RJ Shahian, DM Miller, LG Shapiro, MF Benharash, P McKinnell, JA AF Hsiue, Peter P. Gregson, Aric L. Injean, Patil Vangala, Sitaram Brindis, Ralph G. Shemin, Richard J. Shahian, David M. Miller, Loren G. Shapiro, Martin F. Benharash, Peyman McKinnell, James A. TI Variation in Antibiotic Prophylaxis Selection for Coronary Artery Bypass Graft Procedures in an Era of Increasing Methicillin-Resistant Staphylococcus aureus Prevalence SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Letter ID SURGICAL SITE INFECTION; CARDIAC-SURGERY; METAANALYSIS C1 [Hsiue, Peter P.; Gregson, Aric L.; Injean, Patil; Vangala, Sitaram] Univ Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Dept Med, Los Angeles, CA 90095 USA. [Brindis, Ralph G.] Univ Calif San Francisco, Philip R Lee Inst Hlth Policy Studies, San Francisco, CA 94143 USA. [Shemin, Richard J.; Benharash, Peyman] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Cardiothorac Surg, Los Angeles, CA 90095 USA. [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Miller, Loren G.; McKinnell, James A.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA. [Shapiro, Martin F.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. RP McKinnell, JA (reprint author), Harbor UCLA Med Ctr, Infect Dis Clin Outcomes Res Unit, Div Infect Dis, Los Angeles Biomed Res Inst, 1124 West Carson St, Torrance, CA 90502 USA. EM dr.mckinnell@yahoo.com OI Gregson, Aric/0000-0001-6806-0868 FU NCATS NIH HHS [KL2TR000122, KL2 TR000122]; NHLBI NIH HHS [K23 HL102220, 5K23HL 102220-02] NR 10 TC 1 Z9 1 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUN 1 PY 2014 VL 35 IS 6 BP 737 EP 740 DI 10.1086/676436 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA AG8UK UT WOS:000335693500018 PM 24799655 ER PT J AU Villar, J Kacmarek, RM Guerin, C AF Villar, Jesus Kacmarek, Robert M. Guerin, Claude TI Clinical trials in patients with the acute respiratory distress syndrome: Burn after reading SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID ACUTE LUNG INJURY; DEFINITION C1 [Villar, Jesus] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus] Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Las Palmas Gran Canaria 35010, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesiol, Boston, MA 02115 USA. [Guerin, Claude] Hop Croix Rousse, Serv Reanimat Med, F-69004 Lyon, France. RP Villar, J (reprint author), Hosp Univ Dr Negrin, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Res Unit, Barranco Ballena S-N,4th Floor,South Wing, Las Palmas Gran Canaria 35010, Spain. EM jesus.villar54@gmail.com; rkacmarek@partners.org; claude.guerin@chu-lyon.fr NR 11 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD JUN PY 2014 VL 40 IS 6 BP 900 EP 902 DI 10.1007/s00134-014-3288-6 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA AH6ZJ UT WOS:000336281100020 PM 24718644 ER PT J AU Labarere, J Renaud, B Fine, MJ AF Labarere, Jose Renaud, Bertrand Fine, Michael J. TI Erratum to: How to derive and validate clinical prediction models for use in intensive care medicine (vol 40, pg 513, 2014) SO INTENSIVE CARE MEDICINE LA English DT Correction C1 [Labarere, Jose] Univ Hosp, Qual Care Unit, F-38043 Grenoble, France. [Labarere, Jose] Univ Grenoble 1, CNRS, TIMC, UMR 5525, Grenoble, France. [Renaud, Bertrand] Cochin Hosp, AP HP, Emergency Dept, Paris, France. [Renaud, Bertrand] Hop Hotel Dieu, AP HP, Emergency Dept, F-75181 Paris, France. [Renaud, Bertrand] Fac Med Paris Descartes, Paris, France. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Vet Affairs Ctr Hlth Equity & Res Promot, Pittsburgh, PA USA. [Fine, Michael J.] Univ Pittsburgh, Med Ctr, Div Gen Internal Med, Pittsburgh, PA USA. [Labarere, Jose] UQEM, F-38043 Grenoble 9, France. RP Labarere, J (reprint author), UQEM, Pavillon Taillefer,CHU BP217, F-38043 Grenoble 9, France. EM JLabarere@chu-grenoble.fr RI Labarere, Jose/N-1688-2014 NR 1 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 EI 1432-1238 J9 INTENS CARE MED JI Intensive Care Med. PD JUN PY 2014 VL 40 IS 6 BP 925 EP 925 DI 10.1007/s00134-014-3271-2 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA AH6ZJ UT WOS:000336281100033 ER PT J AU Hinds, O Wighton, P Tisdall, MD Hess, A Breiter, H van der Kouwe, A AF Hinds, Oliver Wighton, Paul Tisdall, M. Dylan Hess, Aaron Breiter, Hans van der Kouwe, Andre TI Neurofeedback Using Functional Spectroscopy SO INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY LA English DT Article DE biofeedback; spectroscopy; fMRI ID REAL-TIME FMRI; CORTEX; ACQUISITION; COMBINATION; DEPENDENCE; MOTION; TESLA; EPI AB Neurofeedback based on real-time measurement of the blood oxygenation level-dependent (BOLD) signal has potential for treatment of neurological disorders and behavioral enhancement. Commonly used methods are based on functional magnetic resonance imaging (fMRI) sequences that sacrifice speed and accuracy for whole-brain coverage, which is unnecessary in most applications. We present multivoxel functional spectroscopy (MVFS): a system for computing the BOLD signal from multiple volumes of interest (VOI) in real-time that improves speed and accuracy of neurofeedback. MVFS consists of a FS pulse sequence, a BOLD reconstruction component, a neural activation estimator, and a stimulus system. The FS pulse sequence is a single-voxel, magnetic resonance spectroscopy sequence without water suppression that has been extended to allow acquisition of a different VOI at each repetition and real-time subject head motion compensation. The BOLD reconstruction component determines the T2* decay rate, which is directly related to BOLD signal strength. The neural activation estimator discounts nuisance signals and scales the activation relative to the amount of ROI noise. Finally, the neurofeedback system presents neural activation-dependent stimuli to experimental subjects with an overall delay of less than 1 s. Here, we present the MVFS system, validation of certain components, examples of its usage in a practical application, and a direct comparison of FS and echo-planar imaging BOLD measurements. We conclude that in the context of realtime BOLD imaging, MVFS can provide superior accuracy and temporal resolution compared with standard fMRI methods. (c) 2014 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 24, 138-148, 2014 C1 [Hinds, Oliver] MIT, McGovern Inst Brain Res, Athinoula A Martinos Imaging Ctr, Cambridge, MA 02139 USA. [Wighton, Paul; Tisdall, M. Dylan; van der Kouwe, Andre] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Imaging Ctr, Charlestown, MA 02129 USA. [Wighton, Paul; Tisdall, M. Dylan; van der Kouwe, Andre] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Hess, Aaron] Univ Cape Town, Dept Human Biol, MRC UCT Med Imaging Res Unit, ZA-7925 Cape Town, Western Cape, South Africa. [Breiter, Hans] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Breiter, Hans] Northwestern Univ, Feinberg Sch Med, Dept Psychiat & Behav Sci, Chigaco, IL USA. RP Wighton, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Imaging Ctr, Charlestown, MA 02129 USA. EM pwighton@nmr.mgh.harvard.edu OI Hess, Aaron/0000-0002-9289-5619 FU NIH [R33DA026104, R21MH096559, R01HD071664, P41RR014075, S10RR021110]; Ellison Medical Foundation FX NIH grants (R33DA026104, R21MH096559, R01HD071664, P41RR014075, S10RR021110 and the Ellison Medical Foundation) NR 29 TC 0 Z9 0 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-9457 EI 1098-1098 J9 INT J IMAG SYST TECH JI Int. J. Imaging Syst. Technol. PD JUN PY 2014 VL 24 IS 2 BP 138 EP 148 DI 10.1002/ima.22088 PG 11 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA AG8JY UT WOS:000335665900003 PM 24999293 ER PT J AU Sunpath, H Winternheimer, P Cohen, S Tennant, I Chelin, N Gandhi, RT Murphy, RA AF Sunpath, H. Winternheimer, P. Cohen, S. Tennant, I. Chelin, N. Gandhi, R. T. Murphy, R. A. TI Double-dose lopinavir-ritonavir in combination with rifampicin-based anti-tuberculosis treatment in South Africa SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE second-line ART; toxicity; co-infection ID HEALTHY-VOLUNTEERS; LOPINAVIR/RITONAVIR; THERAPY AB BACKGROUND: The optimal treatment for tuberculosis (TB) in human immunodeficiency virus (HIV) infected patients in resource-poor settings receiving lopinavir-ritonavir (LPV/r) based second-line antiretroviral therapy (ART) has yet to be determined. In South Africa, clinicians are advised to use 'double-dose' LPV/r dosed at 800 mg/200 mg twice daily during anti-tuberculosis treatment. METHODOLOGY AND PRINCIPLE FINDINGS: We conducted a retrospective study of HIV-infected patients who received >= 2 months of double-dose LPV/r-based ART during concomitant rifampicin-containing anti-tuberculosis treatment. We used standard definitions for TB and HIV outcomes; virological failure was defined as a viral load >1000 copies/ml. During co-administration, gastro-intestinal toxicity occurred in 9/25 (36%) patients, a symptomatic rise in aspartate aminotransferase or alanine aminotransferase of any grade was noted in 3 (12%), with two Grade 3 events, and 3 (12%) patients required treatment discontinuation. Outcomes were favourable, with 20/25 (80%) patients achieving TB treatment success and virological failure observed among 3 (12%) patients during co-administration. CONCLUSION: We found the use of double-dose LPV/r during simultaneous standard anti-tuberculosis treatment to be an effective and reasonably well tolerated interim strategy. C1 [Sunpath, H.; Chelin, N.] McCord Hosp, Durban, South Africa. [Sunpath, H.; Winternheimer, P.] St Vincent Hosp, Indianapolis, IN USA. [Cohen, S.] NYU, Sch Med, Dept Med, New York, NY USA. [Tennant, I.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Gandhi, R. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gandhi, R. T.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Murphy, R. A.] Albert Einstein Coll Med, New York, NY USA. [Murphy, R. A.] Doctors Borders, New York, NY USA. RP Sunpath, H (reprint author), McCord Hosp, Durban, South Africa. EM henrysunpath@yebo.co.za FU Global Health Development, New York University School of Medicine, New York, NY, USA FX Funding for SC was provided by the Global Health Development, New York University School of Medicine, New York, NY, USA. NR 13 TC 3 Z9 3 U1 0 U2 3 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 EI 1815-7920 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD JUN PY 2014 VL 18 IS 6 BP 689 EP 693 DI 10.5588/ijtld.13.0492 PG 5 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA AH5VH UT WOS:000336198700013 PM 24903940 ER PT J AU Shipherd, JC Clum, G Suvak, M Resick, PA AF Shipherd, Jillian C. Clum, Gretchen Suvak, Michael Resick, Patricia A. TI Treatment-related reductions in PTSD and changes in physical health symptoms in women SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Health; Cognitive behavioral therapy; Health habits; Allostatic load; Posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; PROLONGED EXPOSURE THERAPY; SELF-REPORTED HEALTH; QUALITY-OF-LIFE; CHRONIC PAIN; ALLOSTATIC LOAD; PRIMARY-CARE; INTERPERSONAL VIOLENCE; SEXUAL-HARASSMENT AB This study examined the relationship between change in posttraumatic stress disorder (PTSD) symptoms over the course of PTSD treatment and the association with changes in general physical health symptoms. Both positive health habits (e.g., exercise) and negative (e.g., smoking), were examined to determine if they accounted for the association between changes in PTSD severity over time and changes in physical health. Participants were 150 women seeking treatment for PTSD. Latent growth curve modeling indicated a substantial relationship (R (2) = 34 %) between changes in PTSD and changes in physical health that occurred during and shortly following treatment for PTSD. However, there was no evidence to suggest that changes in health behaviors accounted for this relationship. Thus, PTSD treatment can have beneficial effects on self-reported physical health symptoms, even without direct treatment focus on health per se, and is not accounted for by shifts in health behavior. C1 [Shipherd, Jillian C.; Suvak, Michael; Resick, Patricia A.] VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, Boston, MA 02130 USA. [Shipherd, Jillian C.; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02130 USA. [Clum, Gretchen] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Global Community Hlth & Behav Sci, New Orleans, LA 70112 USA. [Suvak, Michael] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. RP Shipherd, JC (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA. EM Jillian.Shipherd@va.gov; gclum@tulane.edu; msuvak@suffolk.edu; Patricia.Resick@va.gov FU NIMH NIH HHS [R01 MH051509, 2-R01-MH51509] NR 65 TC 3 Z9 3 U1 7 U2 25 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 EI 1573-3521 J9 J BEHAV MED JI J. Behav. Med. PD JUN PY 2014 VL 37 IS 3 BP 423 EP 433 DI 10.1007/s10865-013-9500-2 PG 11 WC Psychology, Clinical SC Psychology GA AH7SE UT WOS:000336333300007 PM 23471544 ER PT J AU Carper, MM Traeger, L Gonzalez, JS Wexler, DJ Psaros, C Safren, SA AF Carper, Matthew M. Traeger, Lara Gonzalez, Jeffrey S. Wexler, Deborah J. Psaros, Christina Safren, Steven A. TI The differential associations of depression and diabetes distress with quality of life domains in type 2 diabetes SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Diabetes; T2DM; Quality of life; QOLI; Depression; Diabetes distress ID GLYCEMIC CONTROL; METAANALYSIS; ADULTS; SCALE; SATISFACTION; INSTRUMENTS; MORTALITY; SYMPTOMS; MELLITUS AB The present investigation aimed to understand quality of life domains relevant to adults with type 2 diabetes mellitus (T2DM), and the relative associations of depression and diabetes distress with these domains. Participants were 146 individuals with T2DM who were recruited for entry into a randomized controlled trial of cognitive behavioral therapy for adherence and depression. We conducted an exploratory factor analysis on the Quality of Life Inventory (QOLI) to establish domains of quality of life relevant to this patient population. Hierarchical multiple regression models were evaluated for each domain that emerged to determine independent associations of depression severity and diabetes distress with quality of life independent of demographic and illness factors. Results suggested four quality of life domains: achievement, psychosocial growth, interpersonal relationships, and environment, accounting for 60.1 % of variance in total QOLI scores. Depression severity was associated with poorer quality of life on the achievement, psychosocial growth, and environment domains (p's < 0.01), while diabetes distress was associated with poorer quality of life on the achievement (p < 0.001) domain and marginally associated with quality of life on the psychosocial growth (p < 0.10) domain. Interventions designed to address both depression and diabetes distress may lead to better quality of life outcomes than a generalized depression intervention or an intervention for diabetes alone. C1 [Carper, Matthew M.; Traeger, Lara; Psaros, Christina; Safren, Steven A.] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. [Traeger, Lara; Wexler, Deborah J.; Psaros, Christina; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Gonzalez, Jeffrey S.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA. [Gonzalez, Jeffrey S.] Yeshiva Univ Albert Einstein Coll Med, Diabet Res Ctr, Bronx, NY 10461 USA. [Wexler, Deborah J.] Massachusetts Gen Hosp, Diabet Res Ctr, Boston, MA 02114 USA. [Carper, Matthew M.] Temple Univ, Dept Psychol, Child & Adolescent Anxiety Disorders Clin, Philadelphia, PA 19122 USA. RP Carper, MM (reprint author), Temple Univ, Dept Psychol, Child & Adolescent Anxiety Disorders Clin, 1701 N 13th St, Philadelphia, PA 19122 USA. EM matthew.carper@temple.edu OI Carper, Matthew/0000-0001-7125-9851 FU NCRR NIH HHS [UL1 RR 025758, UL1 RR025758]; NIDDK NIH HHS [P30 DK020541, P60 DK020541, DK 020541]; NIMH NIH HHS [R01MH078571, K24 MH094214, R01 MH078571] NR 34 TC 9 Z9 10 U1 3 U2 23 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 EI 1573-3521 J9 J BEHAV MED JI J. Behav. Med. PD JUN PY 2014 VL 37 IS 3 BP 501 EP 510 DI 10.1007/s10865-013-9505-x PG 10 WC Psychology, Clinical SC Psychology GA AH7SE UT WOS:000336333300014 PM 23515932 ER PT J AU Yu, EW Kumbhani, R Siwila-Sackman, E DeLelys, M Preffer, FI Leder, BZ Wu, JY AF Yu, Elaine W. Kumbhani, Ruchit Siwila-Sackman, Erica DeLelys, Michelle Preffer, Frederic I. Leder, Benjamin Z. Wu, Joy Y. TI Teriparatide ( PTH1-34) Treatment Increases Peripheral Hematopoietic Stem Cells in Postmenopausal Women SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE HEMATOPOIETIC STEM CELL NICHE; PARATHYROID HORMONE; TERIPARATIDE; B CELL LYMPHOPOIESIS ID PARATHYROID-HORMONE; BONE-MARROW; PROGENITOR CELLS; LINING CELLS; NICHE; OSTEOCYTES; TRIAL; MICE; MOBILIZATION; OSTEOBLASTS AB Cells of the osteoblast lineage play an important role in regulating the hematopoietic stem cell (HSC) niche and early B-cell development in animal models, perhaps via parathyroid hormone (PTH)-dependent mechanisms. There are few human clinical studies investigating this phenomenon. We studied the impact of long-term daily teriparatide (PTH 1-34) treatment on cells of the hematopoietic lineage in postmenopausal women. Twenty-three postmenopausal women at high risk of fracture received teriparatide 20 mcg sc daily for 24 months as part of a prospective longitudinal trial. Whole blood measurements were obtained at baseline, 3, 6, 12, and 18 months. Flow cytometry was performed to identify hematopoietic subpopulations, including HSCs (CD34+/CD45(moderate); ISHAGE protocol) and early transitional B cells (CD19+, CD27-, IgD+, CD24[hi], CD38[hi]). Serial measurements of spine and hip bone mineral density (BMD) as well as serum P1NP, osteocalcin, and CTX were also performed. The average age of study subjects was 64 +/- 5 years. We found that teriparatide treatment led to an early increase in circulating HSC number of 40%+/- 14% (p=0.004) by month 3, which persisted to month 18 before returning to near baseline by 24 months. There were no significant changes in transitional B cells or total B cells over the course of the study period. In addition, there were no differences in complete blood count profiles as quantified by standard automated flow cytometry. Interestingly, the peak increase in HSC number was inversely associated with increases in bone markers and spine BMD. Daily teriparatide treatment for osteoporosis increases circulating HSCs by 3 to 6 months in postmenopausal women. This may represent a proliferation of marrow HSCs or increased peripheral HSC mobilization. This clinical study establishes the importance of PTH in the regulation of the HSC niche within humans. (c) 2014 American Society for Bone and Mineral Research. C1 [Yu, Elaine W.; Kumbhani, Ruchit; Siwila-Sackman, Erica; Leder, Benjamin Z.; Wu, Joy Y.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [DeLelys, Michelle; Preffer, Frederic I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wu, Joy Y.] Stanford Univ, Sch Med, Div Endocrinol, Stanford, CA 94305 USA. RP Wu, JY (reprint author), 300 Pasteur Dr,S-025, Stanford, CA 94305 USA. EM bzleder@partners.org; jywu1@stanford.edu FU NIH [AR54741, OD008466, AR61228]; Amgen Inc.; Eli Lilly Co. FX We thank Dr Henry Kronenberg for his helpful discussion and critical review of the manuscript. This work was supported by NIH grants AR54741 and OD008466 (to JYW) and AR61228, and funding support from Amgen Inc. and Eli Lilly Co. The clinical trial registration number is NCT00926380. NR 28 TC 6 Z9 6 U1 0 U2 3 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 JUN PY 2014 VL 29 IS 6 BP 1380 EP 1386 DI 10.1002/jbmr.2171 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AH3DJ UT WOS:000336001500010 PM 24420643 ER PT J AU Bianchi, MT Westover, MB AF Bianchi, Matt T. Westover, Michael Brandon TI Insomnia and Morning Motor Vehicle Accidents A Decision Analysis of the Risk of Hypnotics Versus the Risk of Untreated Insomnia SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID DRIVING IMPAIRMENT; BENZODIAZEPINES; ALCOHOL; IMPACT C1 [Bianchi, Matt T.; Westover, Michael Brandon] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM mtbianchi@partners.org NR 17 TC 0 Z9 0 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 EI 1533-712X J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2014 VL 34 IS 3 BP 400 EP 402 DI 10.1097/JCP.0000000000000134 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA AH3AR UT WOS:000335994100034 PM 24743722 ER PT J AU Siddiqui, A Nagy, PG Bonekamp, D Dreyer, KJ AF Siddiqui, Adeel Nagy, Paul G. Bonekamp, David Dreyer, Keith J. TI Changes to Stage 1 Meaningful Use in 2014: Impact on Radiologists SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE Meaningful Use; Stage 2; 2014 Base EHR; Certified electronic health record; Complete EHR; Electronic health records; Meaningful Use in radiology AB The goal of this work is to provide radiologists an update regarding changes to stage 1 of meaningful use in 2014. These changes were promulgated in the final rulemaking released by the Centers for Medicare and Medicaid Services and the Office of the National Coordinator for Health Information Technology in September 2012. Under the new rules, radiologists are exempt from meaningful use penalties provided that they are listed as radiologists under the Provider Enrollment, Chain and Ownership System (PECOS). A major caveat is that this exemption can be removed at any time. Additional concerns are discussed in the main text. Additional changes discussed include software editions independent of meaningful use stage (i.e., 2011 edition versus 2014 edition), changes to the definition of certified electronic health record technology (CEHRT), and changes to specific measures and exemptions to those measures. The new changes regarding stage 1 add complexity to an already complex program, but overall make achieving meaningful use a win-win situation for radiologists. There are no penalties for failure and incentive payments for success. The cost of upgrading to CEHRT may be much less than the incentive payments, adding a potential new source of revenue. Additional benefits may be realized if the radiology department can build upon a modern electronic health record to improve their practice and billing patterns. Meaningful use and electronic health records represent an important evolutionary step in US healthcare, and it is imperative that radiologists are active participants in the process. C1 [Siddiqui, Adeel] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Nagy, Paul G.; Bonekamp, David; Dreyer, Keith J.] Johns Hopkins Univ, Russell H Morgan Dept Radiol, Ellicott City, MD USA. [Dreyer, Keith J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Siddiqui, A (reprint author), Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. EM adeelsiddiquimd@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0897-1889 EI 1618-727X J9 J DIGIT IMAGING JI J. Digit. Imaging PD JUN PY 2014 VL 27 IS 3 BP 292 EP 296 DI 10.1007/s10278-014-9673-4 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH8PN UT WOS:000336400300002 PM 24682743 ER PT J AU Underhill, ML Crotser, CB AF Underhill, Meghan L. Crotser, Cheryl B. TI Seeking Balance: Decision Support Needs of Women Without Cancer and a Deleterious BRCA1 or BRCA2 Mutation SO JOURNAL OF GENETIC COUNSELING LA English DT Article DE Decision support; Hereditary breast and ovarian cancer syndrome; Patient centered care ID RANDOMIZED-TRIAL; BREAST-CANCER; HEREDITARY BREAST; RISK-ASSESSMENT; CARRIERS; AID; OOPHORECTOMY; INTERVENTION; PERSPECTIVES; MASTECTOMY AB Recommendations for women with a deleterious BRCA1 or BRCA2 gene mutation include complex medical approaches related to cancer risk reduction and detection. Current science has not yet fully elucidated decision support needs that women face when living with medical consequences associated with known hereditary cancer risk. The purpose of this study was to describe health communication and decision support needs in healthy women with BRCA1/2 gene mutations. The original researchers completed an interpretive secondary qualitative data analysis of 23 phenomenological narratives collected between 2008 and 2010. The Ottawa Decision Support and Patient Centered Communication frameworks guided the study design and analysis. Women described a pattern wherein breast and ovarian cancer risk, health related recommendations and decisions, and personal values were prioritized over time based on life contexts. Knowing versus acting on cancer risk was not a static process but an ongoing balancing act of considering current and future personal and medical values, further compounded by the complexity of recommendations. Women shared stories of anticipatory, physical and psychosocial consequences of the decision making experience. The findings have potential to generate future research questions and guide intervention development. Importantly, findings indicate a need for ongoing, long-term, support from genetics professionals and decision support interventions, which challenges the current practice paradigm. C1 [Underhill, Meghan L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. [Crotser, Cheryl B.] Roberts Wesleyan Coll, Sch Nursing, Rochester, NY USA. RP Underhill, ML (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, 450 Brookline Ave,L522, Boston, MA 02115 USA. EM meghanl_underhill@dfci.harvard.edu FU National Cancer Institute through University of Massachusetts Boston [NCIU54CA156732]; National Cancer Institute through Dana Farber Cancer Institute; National Cancer Institute through Phyllis F. Cantor Center FX Funding for Dr. Underhill to complete data analysis was provided by the National Cancer Institute Cancer & Health Disparities Fellowship Funding (NCIU54CA156732) through the University of Massachusetts Boston and Dana Farber Cancer Institute and through the Phyllis F. Cantor Center. Dr. Cheryl Crotser is the Charles S. Gallaher Chair for in the Department of Nursing at Roberts Wesleyan College. NR 36 TC 1 Z9 2 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1059-7700 EI 1573-3599 J9 J GENET COUNS JI J. Genet. Couns. PD JUN PY 2014 VL 23 IS 3 BP 350 EP 362 DI 10.1007/s10897-013-9667-2 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA AH7SQ UT WOS:000336334600008 PM 24271037 ER PT J AU Mills, R Barry, W Haga, SB AF Mills, Rachel Barry, William Haga, Susanne B. TI Public Trust in Genomic Risk Assessment for Type 2 Diabetes Mellitus SO JOURNAL OF GENETIC COUNSELING LA English DT Article DE Genetic counseling; Genomic testing; Type 2 diabetes; Patient trust; Personalized medicine ID BREAST-CANCER SUSCEPTIBILITY; RANDOMIZED CONTROLLED-TRIAL; ONLINE HEALTH INFORMATION; NATIONAL TRENDS SURVEY; ETHNIC DISPARITIES; AFRICAN-AMERICANS; BEHAVIORAL-RESPONSE; RACIAL-DIFFERENCES; GENETICS SERVICES; CARE PROVIDERS AB Patient trust in personal medical information is critical to increasing adherence to physician recommendations and medications. One of the anticipated benefits of learning of one's genomic risk for common diseases is the increased adoption of screening, preventive care and lifestyle changes. However, the equivocal results thus far reported of the positive impact of knowledge of genomic risk on behavior change may be due to lack of patients' trust in the results. As part of a clinical study to compare two methods of communication of genomic risk results for Type 2 diabetes mellitus (T2DM), we assessed patients' trust and preferred methods of delivery of genomic risk information. A total of 300 participants recruited from the general public in Durham, NC were randomized to receive their genomic risk for T2DM in-person from a genetic counselor or online through the testing company's web-site. Participants completed a baseline survey and three follow-up surveys after receiving results. Overall, participants reported high levels of trust in the test results. Participants who received their results in-person from the genetic counselor were significantly more likely to trust their results than those who reviewed their results on-line (p = 0.005). There was not a statistically significant difference in levels of trust among participants with increased genetic risk, as compared to other those with decreased or same as population risk (p = 0.1154). In the event they undergo genomic risk testing again, 55 % of participants overall indicated they would prefer to receive their results online compared to 28 % that would prefer to receive future results in-person. Of those participants preferring to receive results online, 77 % indicated they would prefer to have the option to speak to someone if they had questions with the online results (compared to accessing results online without the option of professional consultation). This is the first study to assess satisfaction with genomic risk testing by the method of delivery of the test result. The higher rate of trust in results delivered in-person suggests that online access reports may not result in serious consideration of results and lack of adoption of recommended preventive recommendations. C1 [Mills, Rachel; Haga, Susanne B.] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC 27708 USA. [Barry, William] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Mills, R (reprint author), Duke Univ, Duke Inst Genome Sci & Policy, 304 Res Dr,Box 90141, Durham, NC 27708 USA. EM r.mills@duke.edu OI Mills, Rachel/0000-0003-4420-9503 FU U.S. National Institutes of Health [1R21HL096573-01A1] FX This work was funded by the U.S. National Institutes of Health (1R21HL096573-01A1) and was partially presented as a poster presentation at the 2012 National Society of Genetic Counselors Annual Education Conference. We are grateful for the statistical support provided by Dr. Sunil Suchindran. Disclosures: R.M provides contracting services for the laboratory testing company GeneDx. W. B. declares no conflict of interest. S. B. H. serves as a consultant to the Inova Translational Medicine Institute of Inova Health Care Services (non-profit). NR 72 TC 0 Z9 0 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1059-7700 EI 1573-3599 J9 J GENET COUNS JI J. Genet. Couns. PD JUN PY 2014 VL 23 IS 3 BP 401 EP 408 DI 10.1007/s10897-013-9674-3 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA AH7SQ UT WOS:000336334600012 PM 24292896 ER PT J AU Goveas, JS Espeland, MA Hogan, PE Tindle, HA Shih, RA Kotchen, JM Robinson, JG Barnes, DE Resnick, SM AF Goveas, Joseph S. Espeland, Mark A. Hogan, Patricia E. Tindle, Hilary A. Shih, Regina A. Kotchen, Jane M. Robinson, Jennifer G. Barnes, Deborah E. Resnick, Susan M. TI Depressive Symptoms and Longitudinal Changes in Cognition: Women's Health Initiative Study of Cognitive Aging SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE depression; cognitive decline; vascular risk factors; cardiovascular disease; women; dementia; depressive symptoms ID LATE-LIFE DEPRESSION; APOLIPOPROTEIN-E GENOTYPE; PRIMARY-CARE PATIENTS; GERIATRIC DEPRESSION; VASCULAR DEPRESSION; POSTMENOPAUSAL WOMEN; ALZHEIMER-DISEASE; IMPAIRMENT; DEMENTIA; RISK AB Elevated depressive symptoms (DS) are associated with incident mild cognitive impairment and probable dementia in postmenopausal women. We examined the association of elevated DS with domain-specific cognitive changes and the moderating role of cardiovascular risk factor severity and cardiovascular disease (CVD). A total of 2221 elderly women who participated in the Women's Health Initiative Study of Cognitive Aging were separated into those with (N = 204) and without (N = 2017) elevated DS. The DS and multidomain cognitive outcomes were measured annually for an average follow-up of 5.04 years. Women with elevated DS showed baseline multidomain cognitive deficits but longitudinal declines in global cognition only. Persistent DS was related to greater global cognition, verbal knowledge and fluency, and memory declines. Significant DS-CVD interactions were observed cross-sectionally (but not longitudinally) for figural memory and fine motor speed. Future studies should investigate the role of nonvascular mechanisms linking DS and cognitive decline. C1 [Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. [Espeland, Mark A.; Hogan, Patricia E.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Tindle, Hilary A.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Shih, Regina A.] RAND Corp, Arlington, VA USA. [Kotchen, Jane M.] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Kotchen, Jane M.] Med Coll Wisconsin, Clin & Translat Sci Inst, Milwaukee, WI 53226 USA. [Robinson, Jennifer G.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat & Epidemiol, San Francisco, CA 94143 USA. [Barnes, Deborah E.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Barnes, Deborah E.] San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA USA. [Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Goveas, JS (reprint author), Med Coll Wisconsin, Dept Psychiat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM jgoveas@mcw.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; Department of Health and Human Services; National Institute on Aging [NO1-AG-1-2106]; Intramural Research Program, National Institute on Aging; National Institutes of Health; Alzheimer's Association [NIRG-11-204070]; Extendicare Foundation; Brain & Behavior Research Foundation (NARSAD); Wyeth Pharmaceuticals; Brain and Behavior Research Foundation (previously NARSAD) young investigator award FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The Women's Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The WHI Study of Cognitive Aging (WHISCA) was supported by the Department of Health and Human Services and the National Institute on Aging (NO1-AG-1-2106). SMR is supported by the Intramural Research Program, National Institute on Aging, and National Institutes of Health. JSG is supported by the Alzheimer's Association New Investigator NIRG-11-204070 and Extendicare Foundation, and previously by Brain & Behavior Research Foundation (NARSAD) young investigator, and Research for a Healthier Tomorrow, a Component of the Advancing a Healthier Wisconsin Endowment at MCW. The Women's Health Initiative Memory Study was funded in part by Wyeth Pharmaceuticals as an ancillary study to the WHI. DB's contributions were supported in part by Brain and Behavior Research Foundation (previously NARSAD) young investigator award. NR 46 TC 11 Z9 11 U1 3 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 EI 1552-5708 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD JUN PY 2014 VL 27 IS 2 BP 94 EP 102 DI 10.1177/0891988714522697 PG 9 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA AH6DG UT WOS:000336220300004 PM 24584465 ER PT J AU Hay, RJ Johns, NE Williams, HC Bolliger, IW Dellavalle, RP Margolis, DJ Marks, R Naldi, L Weinstock, MA Wulf, SK Michaud, C Murray, CJL Naghavi, M AF Hay, Roderick J. Johns, Nicole E. Williams, Hywel C. Bolliger, Ian W. Dellavalle, Robert P. Margolis, David J. Marks, Robin Naldi, Luigi Weinstock, Martin A. Wulf, Sarah K. Michaud, Catherine Murray, Christopher J. L. Naghavi, Mohsen TI The Global Burden of Skin Disease in 2010: An Analysis of the Prevalence and Impact of Skin Conditions SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID SYSTEMATIC ANALYSIS; DISABILITY WEIGHTS; COMMUNITY; SCABIES; ECZEMA; DERMATOLOGY; ETHIOPIA; CRITERIA AB The Global Burden of Disease (GBD) Study 2010 estimated the GBD attributable to 15 categories of skin disease from 1990 to 2010 for 187 countries. For each of the following diseases, we performed systematic literature reviews and analyzed resulting data: eczema, psoriasis, acne vulgaris, pruritus, alopecia areata, decubitus ulcer, urticaria, scabies, fungal skin diseases, impetigo, abscess, and other bacterial skin diseases, cellulitis, viral warts, molluscum contagiosum, and non-melanoma skin cancer. We used disability estimates to determine nonfatal burden. Three skin conditions, fungal skin diseases, other skin and subcutaneous diseases, and acne were in the top 10 most prevalent diseases worldwide in 2010, and eight fell into the top 50; these additional five skin problems were pruritus, eczema, impetigo, scabies, and molluscum contagiosum. Collectively, skin conditions ranged from the 2nd to 11th leading cause of years lived with disability at the country level. At the global level, skin conditions were the fourth leading cause of nonfatal disease burden. Using more data than has been used previously, the burden due to these diseases is enormous in both high- and low-income countries. These results argue strongly to include skin disease prevention and treatment in future global health strategies as a matter of urgency. C1 [Hay, Roderick J.] Int Fdn Dermatol, London W1T 5HQ, England. [Johns, Nicole E.; Bolliger, Ian W.; Wulf, Sarah K.; Murray, Christopher J. L.; Naghavi, Mohsen] Univ Washington, Inst Hlth Metr & Evaluat, Washington, DC USA. [Williams, Hywel C.] Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham NG7 2RD, England. [Dellavalle, Robert P.] Denver VA Med Ctr, Dermatol Serv, Denver, CO USA. [Margolis, David J.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Margolis, David J.] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Marks, Robin] Skin & Canc Fdn, Melbourne, Vic, Australia. [Naldi, Luigi] Azienda Osped Papa Giovanni XXIII, Dept Dermatol, Bergamo, Italy. [Weinstock, Martin A.] Brown Univ, Div Dermatoepidemiol, Providence, RI 02912 USA. [Michaud, Catherine] China Med Board, Cambridge, MA USA. RP Hay, RJ (reprint author), Int Fdn Dermatol, 4 Fitzroy Sq, London W1T 5HQ, England. EM roderick.hay@ifd.org RI Bolliger, Ian/C-4207-2016; Naldi, Luigi/K-6343-2016; OI Bolliger, Ian/0000-0001-8055-297X; Naldi, Luigi/0000-0002-3160-2835; Johns, Nicole/0000-0003-4513-4582 NR 29 TC 109 Z9 111 U1 46 U2 88 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 JUN PY 2014 VL 134 IS 6 BP 1527 EP 1534 DI 10.1038/jid.2013.446 PG 8 WC Dermatology SC Dermatology GA AH5TJ UT WOS:000336193700010 PM 24166134 ER PT J AU Ginat, DT Swearingen, B Curry, W Cahill, D Madsen, J Schaefer, PW AF Ginat, Daniel Thomas Swearingen, Brooke Curry, William Cahill, Daniel Madsen, Joseph Schaefer, Pamela W. TI 3 Tesla Intraoperative MRI for Brain Tumor Surgery SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE 3T; intraoperative MRI; glioma; pituitary tumor; laser ablation ID LOW-GRADE GLIOMA; TRANSSPHENOIDAL PITUITARY SURGERY; GLIOBLASTOMA-MULTIFORME; PRELIMINARY EXPERIENCE; INTERVENTIONAL MRI; CLINICAL ARTICLE; IMAGING GUIDANCE; RESECTION; EXTENT; SURVIVAL AB Implementation of intraoperative magnetic resonance imaging (iMRI) has been shown to optimize the extent of resection and safety of brain tumor surgery. In addition, iMRI can help account for the phenomenon of brain shift and can help to detect complications earlier than routine postoperative imaging, which can potentially improve patient outcome. The higher signal-to-noise ratio offered by 3 Tesla (T) iMRI compared with lower field strength systems is particularly advantageous. The purpose of this article is to review the imaging protocols, imaging findings, and technical considerations related to 3T iMRI. To maximize efficiency, iMRI sequences can be tailored to particular types of tumors and procedures, including nonenhancing brain tumor surgery, enhancing brain tumor surgery, transsphenoidal pituitary tumor surgery, and laser ablation. Unique imaging findings on iMRI include the presence of surgically induced enhancement, which can be a potential confounder for residual enhancing tumor, and hyperacute hemorrhage, which tends to have intermediate signal on T1-weighted sequences and high signal on T2-weighted sequences due to the presence of oxyhemoglobin. MR compatibility and radiofrequency shielding pose particularly stringent technical constraints at 3T and influence the design and usage of the surgical suite with iMRI. J. Magn. Reson. Imaging 2014;39:1357-1365. (c) 2013 Wiley Periodicals, Inc. C1 [Ginat, Daniel Thomas] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Swearingen, Brooke; Curry, William; Cahill, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Madsen, Joseph; Schaefer, Pamela W.] Harvard Univ, Sch Med, Dept Neurosurg, Boston Childrens Hosp, Boston, MA USA. RP Ginat, DT (reprint author), 55 Fruit St, Boston, MA 02114 USA. EM ginatd01@gmail.com OI Cahill, Daniel/0000-0003-2552-6546 NR 56 TC 7 Z9 7 U1 0 U2 6 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 JUN PY 2014 VL 39 IS 6 BP 1357 EP 1365 DI 10.1002/jmri.24380 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG5LM UT WOS:000335460500003 PM 24921066 ER PT J AU Bot, AGJ Becker, SJE Bruijnzeel, H Mulders, MAM Ring, D Vranceanu, AM AF Bot, Arjan G. J. Becker, Stephanie J. E. Bruijnzeel, Hanneke Mulders, Marjolein A. M. Ring, David Vranceanu, Ana-Maria TI Creation of the Abbreviated Measures of the Pain Catastrophizing Scale and the Short Health Anxiety Inventory: The PCS-4 and SHAI-5 SO JOURNAL OF MUSCULOSKELETAL PAIN LA English DT Article DE Health anxiety; pain catastrophizing; short form questionnaires ID RANDOMIZED CONTROLLED-TRIAL; ARM PAIN; MUSCULOSKELETAL PAIN; POSTOPERATIVE PAIN; BACK-PAIN; HYPOCHONDRIASIS; ASSOCIATION; DISABILITY; DEPRESSION; THERAPY AB Objective: In patients with arm and upper extremity illness, pain catastrophizing and health anxiety are important factors in disability, pain and patient satisfaction. The aim of this study was to develop a shorter version of the 13-item Pain Catastrophizing Scale [PCS] and 18-item Short Health Anxiety Inventory [SHAI]. Methods: One hundred and sixty-four patients [54% women, mean age of 51 years] with a variety of upper extremity diagnoses enrolled in this study. Patients completed the PCS, the SHAI, the Disabilities of Arm Shoulder and Hand questionnaire [DASH] for disability, the Patient Health Questionnaire-9 [PHQ-9] for depressive symptoms and a scale to measure pain. Inter-correlation analyses were conducted on each of the subscales of the PCS and the SHAI and questions were selected based on the magnitude of their inter-item correlation. Results: Questions 3, 6, 8 and 11 remained in the PCS-4 and showed good internal consistency [alpha = 0.86] and correlated highly with the original PCS [r = 0.96]. Questions 2, 3, 12, 15 and 17 were chosen for the SHAI-5. The SHAI-5 had alpha = 0.67 and had a correlation or r = 0.87 with the SHAI-18. Both the SHAI-5 and PCS-4 had equal correlations with DASH, PHQ and pain as the original questionnaires. Conclusions: We found that the PCS-4 and SHAI-5 were comparable to the original questionnaires, but further studies should be conducted in order to confirm our findings. This study provides preliminary evidence that the PCS-4 and SHAI-5 could be used to screen for health anxiety and pain catastrophizing in busy orthopedic settings. C1 [Bot, Arjan G. J.; Becker, Stephanie J. E.; Bruijnzeel, Hanneke; Mulders, Marjolein A. M.; Ring, David] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. [Bot, Arjan G. J.; Becker, Stephanie J. E.; Ring, David; Vranceanu, Ana-Maria] Harvard Univ, Sch Med, Boston, MA USA. [Vranceanu, Ana-Maria] Massachusetts Gen Hosp, Benson Henry Mind Body Inst, Dept Behav Med, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org RI Becker, Stephanie/N-5761-2014 FU VSB fonds; Prins Bernhard CultuurFonds/Banning de Jong Fonds; Anna Fonds travel grant; Anna Fonds; Genootschap Noorthey; Vreedefonds''; Wright Medical Technology Inc.; Biomet; Skeletal Dynamics; Hand Surgery Fellowship from AO North America; Orthopedic Association of Trauma (OTA) FX Arjan G.J. Bot has received grants from "VSB fonds'', "Prins Bernhard CultuurFonds/Banning de Jong Fonds'', both non-medical grants and the orthopaedic: "Anna Fonds travel grant''; Stephanie J.E. Becker has received grants from "Anna Fonds'', "Genootschap Noorthey'' and "Vreedefonds''.; Hanneke Bruijnzeel has received a grant from "Anna Fonds".; Marjolein A. M. Mulders has received a grant from "Anna Fonds''.; David Ring receives royalties from Wright Medical Technology Inc.; is consultant for Wright Medical, Skeletal Dynamics, Biomet; received honoraria from AO North America, AO International; has royalties contracted with Biomet, Skeletal Dynamics; has stock Options in Illuminos; received study specific grants from Skeletal Dynamics (Pending); received funding for Hand Surgery Fellowship from AO North America and is Deputy Editor for Review Articles, Journal of Hand Surgery Am., Deputy Editor for Hand and Wrist, Journal of Orthopaedic Trauma, Assistant Editor, Journal of Shoulder and Elbow Surgery. Ana-Maria Vranceanu received a grant from the Orthopedic Association of Trauma (OTA). NR 44 TC 3 Z9 3 U1 0 U2 5 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1058-2452 J9 J MUSCULOSKELET PAIN JI J. Musculoskelet. Pain PD JUN PY 2014 VL 22 IS 2 BP 145 EP 151 DI 10.3109/10582452.2014.883020 PG 7 WC Rehabilitation; Rheumatology SC Rehabilitation; Rheumatology GA AH8OE UT WOS:000336396600005 ER PT J AU Panizzi, P Stone, JR Nahrendorf, M AF Panizzi, Peter Stone, James R. Nahrendorf, Matthias TI Endocarditis and molecular imaging SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Review ID STAPHYLOCOCCUS-AUREUS ENDOCARDITIS; EXPERIMENTAL INFECTIVE ENDOCARDITIS; IN-VIVO; BACTERIAL-ENDOCARDITIS; MEDICAL PROGRESS; DIAGNOSIS; MANAGEMENT; ANTIBODY; BIOLUMINESCENCE; PROTHROMBIN C1 [Panizzi, Peter] Auburn Univ, Dept Drug Discovery & Dev, Harrison Sch Pharm, Auburn, AL 36849 USA. [Stone, James R.; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Stone, James R.; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu OI Panizzi, Peter/0000-0003-0141-8807 FU National Institutes of Health, National Heart, Lung, and Blood Institute [R00HL094533, R01HL114477]; National Institute of Allergy and Infectious Diseases Grant [2R44AI085840-02] FX This work was supported by the National Institutes of Health through grants provided by the National Heart, Lung, and Blood Institute, R00HL094533 (to P. P.) & R01HL114477 (to P. P. and M.N.), the National Institute of Allergy and Infectious Diseases Grant 2R44AI085840-02 (to P.P.). NR 65 TC 4 Z9 4 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JUN PY 2014 VL 21 IS 3 BP 486 EP 495 DI 10.1007/s12350-014-9902-8 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AH6YI UT WOS:000336278000008 PM 24797384 ER PT J AU Hage, FG Garcia, EV AF Hage, Fadi G. Garcia, Ernest V. TI The independent prognostic value of left ventricular dyssynchrony SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material ID PHASE-ANALYSIS; MECHANICAL DYSSYNCHRONY; CARDIOMYOPATHY; DEATH; ERA C1 [Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. [Garcia, Ernest V.] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30322 USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Lyons Harrison Res Bldg 314,1900 Univ BLVD, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 18 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 EI 1532-6551 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JUN PY 2014 VL 21 IS 3 BP 541 EP 543 DI 10.1007/s12350-014-9878-4 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA AH6YI UT WOS:000336278000013 PM 24623398 ER PT J AU Abramowicz, S Simon, LE Susarla, HK Lee, EY Cheon, JE Kim, S Kaban, LB AF Abramowicz, Shelly Simon, Lisa E. Susarla, Harlyn K. Lee, Edward Y. Cheon, Jung-Eun Kim, Susan Kaban, Leonard B. TI Are Panoramic Radiographs Predictive of Temporomandibular Joint Synovitis in Children With Juvenile Idiopathic Arthritis? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID INVOLVEMENT; PREVALENCE; ULTRASOUND; SIGNS AB Purpose: To identify specific panoramic radiographic findings associated with temporomandibular joint (TMJ) synovitis in children with juvenile idiopathic arthritis (JIA). Materials and Methods: This was a retrospective study of children with JIA evaluated at Boston Children's Hospital. Patients were included if they had a confirmed diagnosis of JIA, a panoramic radiograph, and a contemporaneous TMJ magnetic resonance imaging (MRI) study with contrast. Medical records and imaging studies were reviewed to document demographic, panoramic (accentuated antegonial notch, short ramus and condyle unit [RCU] length, and abnormal condyle morphology: decreased condyle anteroposterior or superoinferior dimension) and MRI findings. The outcome variable was the presence or absence of TMJ synovitis on MRI. Descriptive and bivariate statistics and logistic regression models were used to identify associations (significant at P <= .05). Results: Thirty patients (21 girls) with a mean age of 11.1 years (range, 5 to 16 yr) met the inclusion criteria. Of these, 15 patients had MRI scans positive for synovitis (bilateral in 18 joints in 9 patients and unilateral in 6 joints in 6 patients). The remaining 15 patients did not have evidence of synovitis on MRI. In the synovitis group, 18 of 24 joints (75%) showed abnormal panoramic findings (abnormal condyle morphology in 18 joints, accentuated antegonial notch in 9 joints, or short RCU length in 5 joints). In the nonsynovitis group, 15 of 36 joints (42%) showed abnormal panoramic findings (abnormal condyle morphology in 12 joints, accentuated antegonial notch in 6 joints, or short RCU length in 4 joints). Abnormal condyle morphology and accentuated antegonial notching on panoramic radiographs were found to be significantly correlated with synovitis (P = .0005 and .044, respectively). In a logistic regression model, abnormal condyle morphology was significantly associated with an increase in likelihood of TMJ synovitis versus those joints with normal condyle morphology (P = .007). Joints with abnormal condyle morphology and accentuated antegonial notching were 7.5 times as likely to have synovitis (P = .009) versus those joints without abnormal panoramic findings. Conclusion: Results of this preliminary study indicate that in this sample of children with JIA, the combination of abnormal condyle morphology and accentuated antegonial notching on a panoramic radiograph correlates with TMJ synovitis on MRI. (C) 2014 American Association of Oral and Maxillofacial Surgeons C1 [Abramowicz, Shelly; Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Abramowicz, Shelly] Boston Childrens Hosp, Boston, MA USA. [Simon, Lisa E.; Susarla, Harlyn K.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Lee, Edward Y.] Harvard Univ, Sch Med, Dept Radiol, Boston Childrens Hosp, Boston, MA 02115 USA. [Cheon, Jung-Eun] Seoul Natl Univ, Coll Med, Dept Radiol, Seoul, South Korea. [Cheon, Jung-Eun] Childrens Hosp, Seoul, South Korea. [Kim, Susan] Harvard Univ, Sch Med, Dept Pediat, Rheumatol Program,Boston Childrens Hosp, Boston, MA 02115 USA. [Kaban, Leonard B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Abramowicz, S (reprint author), 1365 Clifton Rd,Bldg B,Suite 2300, Atlanta, GA 30322 USA. EM sabram5@emory.edu FU Oral and Maxillofacial Surgery Foundation/American Association of Maxillofacial Surgeons Faculty Educator Development Award; Massachusetts General Hospital Oral and Maxillofacial Surgery Education and Research Fund; Harvard Medical School's Scholars in Medicine FX This project was supported in part by the Oral and Maxillofacial Surgery Foundation/American Association of Maxillofacial Surgeons Faculty Educator Development Award (to S. A.), the Massachusetts General Hospital Oral and Maxillofacial Surgery Education and Research Fund, and Harvard Medical School's Scholars in Medicine (to L.S.). NR 16 TC 4 Z9 4 U1 1 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2014 VL 72 IS 6 BP 1063 EP 1069 DI 10.1016/j.joms.2013.11.021 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AH3NZ UT WOS:000336032200008 PM 24742698 ER PT J AU Oral, E Neils, A Yabannavar, P Muratoglu, OK AF Oral, Ebru Neils, Andrew Yabannavar, Pooja Muratoglu, Orhun K. TI The Effect of an Additional Phosphite Stabilizer on the Properties of Radiation Cross-Linked Vitamin E Blends of UHMWPE SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE synergy; antioxidant; total joint replacement; hip; knee ID MOLECULAR-WEIGHT POLYETHYLENE; CRACK PROPAGATION RESISTANCE; TOTAL HIP-ARTHROPLASTY; IRRADIATED UHMWPE; ALPHA-TOCOPHEROL; FATIGUE RESISTANCE; WEAR-RESISTANCE; OXIDATION; OSTEOLYSIS; COMPONENTS AB Antioxidant stabilization of radiation cross-linked ultrahigh molecular weight polyethylene (UHMWPE) has been introduced to improve the oxidative stability of total joint implant bearing surfaces. Blending of an antioxidant with UHMWPE resin powder followed by consolidation and radiation cross-linking has been cleared by the FDA for use in both total hips and total knees for designs incorporating two antioxidants, namely vitamin E and Covernox (a medical grade version of Irganox 1010). The antioxidants in the polymer are expected to protect the polymer during consolidation, during radiation cross-linking, on the shelf before implantation, and in vivo after implantation. To maximize the protection of the polymer afforded by the antioxidant in vivo, a novel approach may be the use of multiple antioxidants, especially to protect the primary antioxidant for a longer period of time. We hypothesized that the addition of a phosphite stabilizer (Irgafos 168) commonly used in conjunction with hindered phenolic antioxidants in polymer processing could improve the oxidative stability of radiation cross-linked blends of vitamin E. To test our hypothesis, we prepared UHMWPE blends with 0.05wt% Irgafos and 0.05wt% vitamin E and compared its cross-link density, wear resistance, tensile properties, and impact strength to control blends containing only vitamin E. Our hypothesis was not supported; the cross-link density of UHMWPE was significantly decreased by the additive without additional benefit to oxidative stability. To our knowledge, this was the first attempt at using multiple stabilizers in medical grade UHMWPE. (c) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:757-761, 2014. C1 [Oral, Ebru; Neils, Andrew; Yabannavar, Pooja; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. [Yabannavar, Pooja] MIT, Dept Mat Sci & Engn, Boston, MA USA. RP Oral, E (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. EM eoral@partners.org FU Aston Medical; Corin Ltd.; Corin Ltd., Iconacy; Zimmer; Renovis; Conformis; Mako; Biomet FX No external funds were used for this study. One or more the authors received royalties from Aston Medical, Corin Ltd., Iconacy, Zimmer, Renovis, Conformis, Mako, and Biomet on implant material technology not related to the technology discussed in this study. One of the authors is an unpaid consultant for Biomet. NR 42 TC 1 Z9 1 U1 2 U2 32 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 JUN PY 2014 VL 32 IS 6 BP 757 EP 761 DI 10.1002/jor.22597 PG 5 WC Orthopedics SC Orthopedics GA AE1GC UT WOS:000333716100004 PM 24536024 ER PT J AU Winter, H Heyman, M AF Winter, Harland Heyman, Melvin TI Value of Endoscopic Mucosal Biopsies in Normal-Appearing Colonic Mucosa SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Editorial Material C1 [Winter, Harland; Heyman, Melvin] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Winter, H (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hwinter@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUN PY 2014 VL 58 IS 6 BP 676 EP 677 DI 10.1097/MPG.0000000000000384 PG 2 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AH6SS UT WOS:000336261600008 PM 24866780 ER PT J AU Gosselin, KB Feldman, HA Sonis, AL Bechard, LJ Kellogg, MD Gura, K Venick, R Gordon, CM Guinan, EC Duggan, C AF Gosselin, Kerri B. Feldman, Henry A. Sonis, Andrew L. Bechard, Lori J. Kellogg, Mark D. Gura, Kathleen Venick, Robert Gordon, Catherine M. Guinan, Eva C. Duggan, Christopher TI Serum Citrulline as a Biomarker of Gastrointestinal Function During Hematopoietic Cell Transplantation in Children SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE biomarker; citrulline; gastrointestinal function; hematopoietic cell transplantation ID SHORT-BOWEL SYNDROME; PLASMA CITRULLINE; INTESTINAL FAILURE; ENTEROCYTE MASS; PARENTERAL-NUTRITION; MUCOSITIS; DISEASE; MARKER; PATHOBIOLOGY; CHEMOTHERAPY AB Objectives:We sought to determine whether serum citrulline (CIT), an amino acid produced by small bowel enterocytes, was associated with clinical and biochemical markers of gastrointestinal function in children undergoing hematopoietic cell transplantation (HCT).Methods:We conducted a multicenter, prospective cohort study of 26 children to define time-related changes in serum CIT during the course of HCT. Markers of gastrointestinal function including oral energy intake, emesis, stool volume, presence of graft-versus-host disease (GVHD), oral mucositis severity, and cytokine and neurohormone levels were measured. Weekly serum CIT concentrations were obtained from 10 days prior until 30 days after HCT.Results:Mean baseline CIT concentration was 22.7mol/L (95% confidence interval [CI] 17.7-27.6) on day -10, which decreased to a nadir of 7.5mol/L (95% CI 3.1-18.0, P=0.017) on day 8 following HCT before returning to baseline by day 30. After adjustment for IL-6 level (1.0% lower CIT per 10% increase in interleukin-6, P=0.004), presence of acute GVHD (27% lower CIT, P=0.025), and oral energy intake (2.1% lower CIT per 10% decrease in energy intake, P=0.018), the nadir shifted to day 10, when mean CIT concentration was lower in patients with severe oral mucositis (6.7mol/L, 95% CI 3.4-13.1) than in those without severe mucositis (11.9mol/L, 95% CI 5.8-24.4, P=0.003). Change in CIT was not correlated with stool volume, C-reactive protein, tumor necrosis factor-, leptin, or ghrelin.Conclusions:In children undergoing HCT, serum CIT correlates with measures of gastrointestinal function (oral mucositis severity, dietary intake, acute GVHD) and may reflect mucosal injury to the gastrointestinal tract. C1 [Gosselin, Kerri B.; Feldman, Henry A.; Sonis, Andrew L.; Bechard, Lori J.; Kellogg, Mark D.; Gura, Kathleen; Duggan, Christopher] Boston Childrens Hosp, Boston, MA USA. [Venick, Robert] UCLA Mattel Childrens Hosp, Los Angeles, CA USA. [Gordon, Catherine M.] Brown Univ, Providence, RI 02912 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Duggan, C (reprint author), Boston Childrens Hosp, Ctr Nutr, Div Gastroenterol Hepatol & Nutr, 300 Longwood Ave, Boston, MA 02115 USA. EM christopher.duggan@childrens.harvard.edu FU Massachusetts Vitamin Litigation Grant; Harvard Clinical and Translational Science Center [UL1 RR-025758]; National Institutes of Health [K24 HD 058795, T32 DK 7477-30]; Bill and Melinda Gates Foundation [OPP1066203] FX The present study was supported by the Massachusetts Vitamin Litigation Grant, the Harvard Clinical and Translational Science Center UL1 RR-025758, and National Institutes of Health grants K24 HD 058795 and T32 DK 7477-30. C. D. was supported in part by Bill and Melinda Gates Foundation Award OPP1066203. NR 29 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUN PY 2014 VL 58 IS 6 BP 709 EP 714 DI 10.1097/MPG.0000000000000335 PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA AH6SS UT WOS:000336261600015 PM 24614125 ER PT J AU Erickson, MA Morofuji, Y Owen, JB Banks, WA AF Erickson, Michelle A. Morofuji, Yoichi Owen, Joshua B. Banks, William A. TI Rapid Transport of CCL11 across the Blood-Brain Barrier: Regional Variation and Importance of Blood Cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; COGNITIVE FUNCTION; RAT-BRAIN; EOTAXIN; CAPILLARY; MOUSE; CHEMOKINE; RECEPTOR; PLASMA; NEUROGENESIS AB Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine. C1 [Erickson, Michelle A.] Univ Penn, Dept Pathol, Sch Dent Med, Philadelphia, PA 19104 USA. [Erickson, Michelle A.; Morofuji, Yoichi; Owen, Joshua B.; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Erickson, Michelle A.; Morofuji, Yoichi; Owen, Joshua B.; Banks, William A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. [Owen, Joshua B.] Univ Kentucky, Dept Chem, Lexington, KY 40506 USA. [Morofuji, Yoichi] Nagasaki Univ, Dept Neurosurg, Nagasaki 852, Japan. RP Banks, WA (reprint author), Bldg 1,Rm 810A,1660 Columbian Way, Seattle, WA 98108 USA. EM wabanks1@u.washington.edu FU National Institutes of Health National Institute on Aging [R01-AG029839]; National Institutes of Health National Institute of Neurological Disorders and Stroke [R01NS051334] FX This work was supported by the National Institutes of Health National Institute on Aging [Grant R01-AG029839]; and National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant R01NS051334]. NR 42 TC 13 Z9 13 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2014 VL 349 IS 3 BP 497 EP 507 DI 10.1124/jpet.114.213074 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AH5GJ UT WOS:000336156200014 PM 24706984 ER PT J AU Neuhaus, V Bot, AGJ Swellengrebel, CHJ Jain, NB Warner, JJP Ring, DC AF Neuhaus, Valentin Bot, Arjan G. J. Swellengrebel, Christiaan H. J. Jain, Nitin B. Warner, Jon J. P. Ring, David C. TI Treatment choice affects inpatient adverse events and mortality in older aged inpatients with an isolated fracture of the proximal humerus SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE Comorbidity; complication; operation; proximal humerus fracture; surgery; arthroplasty; open reduction and internal fixation ID SURGICAL-TREATMENT; NONOPERATIVE TREATMENT; CLASSIFICATION; COMPLICATIONS; ARTHROPLASTY; SURGERY; HEMIARTHROPLASTY; EPIDEMIOLOGY; OBESITY; TRENDS AB Background: This study tests the null hypothesis that, among patients aged 65 and older admitted to a United States hospital with an isolated fracture of the proximal humerus (no other injuries or fractures), there are no differences between operative (fixation or arthroplasty) and nonoperative treatments with respect to inpatient adverse events, inpatient mortality, and discharge to a long-term care facility rates accounting for comorbidities. Methods: Using a large national database representing an estimated 132,005 patients aged 65 and older admitted to a US hospital with an isolated proximal humerus fracture between 2003 and 2007. Sixty-one percent did not have surgery, 22% were treated with open reduction and internal fixation (ORIF), and 17% were treated with arthroplasty. Results: The risk of an in hospital adverse event was 21% overall and was 4.4 times greater with arthroplasty and 2.7 times greater with ORIF compared to nonoperative treatment. The risk of in hospital death was 1.8% overall and was 2.8 times greater with ORIF compared to nonoperative treatment. Patients treated operatively were less likely to be discharged to a long-term facility compared to patients treated nonoperatively. Conclusion: In spite of a tendency to treat the most infirm patients (those that are not discharged to home) nonoperatively, operative treatment (open reduction and internal fixation in particular) is an independent risk factor for inpatient adverse events and mortality in older-aged patients admitted to the hospital with an isolated fracture of the proximal humerus and should perhaps be offered more judiciously. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Neuhaus, Valentin; Bot, Arjan G. J.; Swellengrebel, Christiaan H. J.; Ring, David C.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Jain, Nitin B.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Jain, Nitin B.] Harvard Univ, Sch Med, Boston, MA USA. [Jain, Nitin B.; Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. [Jain, Nitin B.] Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA. RP Ring, DC (reprint author), Massachusetts Gen Hosp, Yawkey Ctr, Orthopaed Hand & Upper Extrem Serv, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Neuhaus, Valentin/0000-0003-4012-5628 FU "Gottfried und Julia Bangerter-Rhyner-Stiftung", Switzerland; Prins Bernhard Cultuurfonds/Banning- de Jong fonds; VSB fonds; Anna Fonds, the Netherlands; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [1K23AR059199]; Foundation for PMR; Biomedical Research Institute at Brigham and Women's Hospital FX Valentin Neuhaus, MD, was supported by the "Gottfried und Julia Bangerter-Rhyner-Stiftung", Switzerland, for Scientific Research. Arjan G.J. Bot, MD, was supported by the Prins Bernhard Cultuurfonds/Banning- de Jong fonds, VSB fonds and the Anna Fonds, the Netherlands. Nitin B. Jain, MD, MSPH, is supported by funding from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) project number 1K23AR059199, Foundation for PM&R, and Biomedical Research Institute at Brigham and Women's Hospital. The other authors their immediate families, and any research foundation with which they are affiliated received no financial payments or other benefits from any commercial entity related to the subject of this article. NR 29 TC 7 Z9 7 U1 0 U2 0 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 JUN PY 2014 VL 23 IS 6 BP 800 EP 806 DI 10.1016/j.jse.2013.09.006 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AH8XS UT WOS:000336422100010 PM 24135421 ER PT J AU Vogel, LA Moen, TC Macaulay, AA Arons, RR Cadet, ER Ahmad, CS Levine, WN AF Vogel, Laura A. Moen, Todd C. Macaulay, Alec A. Arons, Raymond R. Cadet, Edwin R. Ahmad, Christopher S. Levine, William N. TI Superior labrum anterior-to-posterior repair incidence: a longitudinal investigation of community and academic databases SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article DE SLAP lesion; incidence; SPARCS; OSHPD; ABOS ID II SLAP LESIONS; GLENOID LABRUM; IISLAP LESIONS; ARTHROSCOPIC TREATMENT; SNYDER CLASSIFICATION; RISING INCIDENCE; LONG HEAD; TEARS; OUTCOMES; BICEPS AB Background: Superior labrum anterior-to-posterior (SLAP) lesion repair is controversial regarding indications and potential complications. Methods: Databases were used to determine the SLAP repair incidence compared with all orthopaedic procedures over a period of 10 years. In part A, the New York Statewide Planning and Research Cooperative System ambulatory surgery database was investigated from 2002 to 2009. In part B, the California Office of Statewide Health Planning and Development ambulatory surgery database was investigated from 2005 to 2009. In part C, the American Board of Orthopaedic Surgery (ABOS) database was investigated from 2003 to 2010. Results: In part A, from 2002 to 2009, there was a 238% increase in SLAP repair volume compared with a 125% increase in all orthopaedic procedures. In part B, from 2005 to 2009, there was a 20.17% increase in SLAP repair volume compared with a decrease of 13.64% in all orthopaedic procedures. In part C, among candidates performing at least 1 SLAP repair, there was no statistically significant difference in likelihood of performing a SLAP repair (95% confidence interval, 0.973-1.003) in 2010 as compared with 2003 (P > .10). Conclusions: There has been a significant increase in the incidence of SLAP repairs in the past 10 years in statewide databases. This pattern was not seen in the ABOS database, in which the annual volume of SLAP repairs remained stable over the same period. This suggests that SLAP lesions have been over-treated with surgical repair but that part II ABOS candidates are becoming more aware of the need to narrow indications. Level of evidence: Epidemiology Study, Database Analysis. (C) 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Vogel, Laura A.; Arons, Raymond R.; Cadet, Edwin R.; Ahmad, Christopher S.; Levine, William N.] New York Presbyterian Columbia Univ Med Ctr, Ctr Shoulder Elbow & Sports Med, Dept Orthopaed Surg, New York, NY 10032 USA. [Moen, Todd C.] WB Carrell Mem Clin, Dallas, TX USA. [Macaulay, Alec A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Levine, WN (reprint author), New York Presbyterian Columbia Univ Med Ctr, Ctr Shoulder Elbow & Sports Med, Dept Orthopaed Surg, 622 W 168th St,PH 1117, New York, NY 10032 USA. EM wnl1@columbia.edu NR 47 TC 5 Z9 5 U1 1 U2 7 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 JUN PY 2014 VL 23 IS 6 BP E119 EP E126 DI 10.1016/j.jse.2013.11.002 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA AH8XS UT WOS:000336422100001 PM 24496049 ER PT J AU Sung, S Kimball, AB AF Sung, Sarah Kimball, Alexa B. TI An evaluation of educational debt levels in dermatology residents and effects on career choices SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 [Sung, Sarah; Kimball, Alexa B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin, 50 Staniford St,Suite 240, Boston, MA 02141 USA. EM Harvardskinstudies@partners.org NR 4 TC 1 Z9 1 U1 0 U2 1 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 JUN PY 2014 VL 70 IS 6 BP 1141 EP 1142 DI 10.1016/j.jaad.2013.09.060 PG 3 WC Dermatology SC Dermatology GA AH3NJ UT WOS:000336030400039 PM 24831320 ER PT J AU Benavidez, OJ Gauvreau, K Geva, T AF Benavidez, Oscar J. Gauvreau, Kimberlee Geva, Tal TI Diagnostic Errors in Congenital Echocardiography: Importance of Study Conditions SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Congenital echocardiography; Diagnostic error; Quality; Outcomes ID HEART-DISEASE; ACCURACY AB Background: Diagnostic errors are unwanted clinical events that place patients at risk for injury. The authors have previously reported that a majority of congenital echocardiography errors have clinical impacts and, on the basis of a small cohort, identified factors associated with diagnostic error. The objectives of this study were (1) to evaluate patient risk factors for diagnostic errors in a large contemporary cohort and (2) to identify risk factors for situation-related diagnostic errors. Methods: Diagnostic errors were identified at a large academic pediatric cardiac center from 2004 to 2011. Clinical and situational variables were collected from diagnostic error cases and controls. Results: Among the 254 diagnostic error cases, 66% affected clinical management or patients experienced adverse events; 77% of errors were preventable or possibly preventable. Coronary arteries, pulmonary veins, and the aortic arch were most commonly involved with diagnostic errors. Multivariate analysis identified the following patient-related risk factors: rare or very rare diagnoses (adjusted odds ratio [AOR], 6.3; P < .001), high anatomic complexity (AOR, 3.4; P < .001), and weight < 5 kg (AOR, 2.7; P < .001). Risk factors related to the setting of the echocardiographic study included evening or night (7 PM to 6: 59 AM) study interpretation (AOR, 2.6; P = .005) and weekend studies (Friday through Sunday) (AOR, 1.6; P = .04). The model area under the receiver operating characteristic curve was 0.833. Conclusions: In addition to patient risk factors, the setting of an echocardiographic study and interpretation contribute to risk for a diagnostic error. Studies interpreted overnight or performed during a weekend should be considered for a quality improvement activity to reduce diagnostic errors or their impact. C1 [Benavidez, Oscar J.] Harvard Univ, Sch Med, Dept Cardiol, Boston Childrens Hosp, Boston, MA USA. [Benavidez, Oscar J.; Gauvreau, Kimberlee; Geva, Tal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Congenital Cardiol, Boston, MA USA. [Benavidez, Oscar J.; Gauvreau, Kimberlee; Geva, Tal] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Benavidez, OJ (reprint author), Massachusetts Gen Hosp, Div Pediat Congenital Cardiol, 175 Cambridge St, Boston, MA 02114 USA. EM ojbenavidez@partners.org FU Robert Wood Johnson Foundation's Harold Amos Medical Faculty Program FX Dr Benavidez is supported a grant from the Robert Wood Johnson Foundation's Harold Amos Medical Faculty Program. NR 11 TC 9 Z9 9 U1 0 U2 1 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 JUN PY 2014 VL 27 IS 6 BP 616 EP 623 DI 10.1016/j.echo.2014.03.001 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH8PD UT WOS:000336399300009 PM 24709004 ER PT J AU Della Corte, A Body, SC Booher, AM Schaefers, HJ Milewski, RK Michelena, HI Evangelista, A Pibarot, P Mathieu, P Limongelli, G Shekar, PS Aranki, SF Ballotta, A Di Benedetto, G Sakalihasan, N Nappi, G Eagle, KA Bavaria, JE Frigiola, A Sundt, TM AF Della Corte, Alessandro Body, Simon C. Booher, Anna M. Schaefers, Hans-Joachim Milewski, Rita K. Michelena, Hector I. Evangelista, Arturo Pibarot, Philippe Mathieu, Patrick Limongelli, Giuseppe Shekar, Prem S. Aranki, Sary F. Ballotta, Andrea Di Benedetto, Giuseppe Sakalihasan, Natzi Nappi, Gianantonio Eagle, Kim A. Bavaria, Joseph E. Frigiola, Alessandro Sundt, Thoralf M. CA Int Bicuspid Aortic Valve Consorti TI Surgical treatment of bicuspid aortic valve disease: Knowledge gaps and research perspectives SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Review ID DILATED ASCENDING AORTA; PRACTICE GUIDELINES; AMERICAN-COLLEGE; NATURAL-HISTORY; EARLIER STAGE; REPLACEMENT; STENOSIS; AORTOPATHY; RISK; DISSECTION C1 [Della Corte, Alessandro; Nappi, Gianantonio] Univ Naples 2, Dept Cardiothorac Sci, Div Cardiac Surg, I-80131 Naples, Italy. [Body, Simon C.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Booher, Anna M.; Eagle, Kim A.] Univ Michigan, Med Ctr, Dept Internal Med, Div Cardiol, Ann Arbor, MI 48109 USA. [Schaefers, Hans-Joachim] Univ Saarland, Med Ctr, Dept Thorac & Cardiovasc Surg, Homburg, Germany. [Milewski, Rita K.; Bavaria, Joseph E.] Hosp Univ Penn, Dept Cardiovasc Surg, Philadelphia, PA 19104 USA. [Michelena, Hector I.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Evangelista, Arturo] Hosp Valle De Hebron, Dept Cardiol, Barcelona, Spain. [Pibarot, Philippe; Mathieu, Patrick] Univ Laval, Quebec City, PQ, Canada. [Limongelli, Giuseppe] Univ Naples 2, Monaldi Hosp, Div Cardiol, I-80131 Naples, Italy. [Shekar, Prem S.; Aranki, Sary F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiac Surg, Boston, MA 02115 USA. [Ballotta, Andrea; Frigiola, Alessandro] IRCCS Policlin San Donato, Dept Cardiac Surg, Milan, Italy. [Di Benedetto, Giuseppe] Univ Hosp, Heart Dept, Salerno, Italy. [Sakalihasan, Natzi] Univ Hosp, Cardiovasc Surg Serv, Liege, Belgium. [Sundt, Thoralf M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA. RP Della Corte, A (reprint author), Univ Naples 2, V Monaldi Hosp, Dept Cardiothorac Sci, Via L Bianchi, I-80131 Naples, Italy. EM aledellacorte@libero.it RI Di Salvo, Giovanni/O-7033-2015; OI Di Salvo, Giovanni/0000-0002-0305-0113; Pluchinotta, Francesca Romana/0000-0001-7185-7157; Della Corte, Alessandro/0000-0002-4636-3339; LImongelli, Giuseppe/0000-0002-8291-9517 FU AbbVie; Thrasos Therapeutics, Inc. FX Simon C. Body reports consulting fees from AbbVie. Kim A. Eagle reports a research grant from Gore. Thoralf M. Sundt reports consulting fees from Thrasos Therapeutics, Inc. All other authors have nothing to disclose with regard to commercial support. NR 75 TC 19 Z9 21 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 2014 VL 147 IS 6 BP 1749 EP U78 DI 10.1016/j.jtcvs.2014.01.021 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AH9HF UT WOS:000336452000014 PM 24534676 ER PT J AU Coselli, JS Volguina, IV LeMaire, SA Sundt, TM Connolly, HM Stephens, EH Schaff, HV Milewicz, DM Vricella, LA Dietz, HC Minard, CG Miller, DC AF Coselli, Joseph S. Volguina, Irina V. LeMaire, Scott A. Sundt, Thoralf M. Connolly, Heidi M. Stephens, Elizabeth H. Schaff, Hartzell V. Milewicz, Dianna M. Vricella, Luca A. Dietz, Harry C. Minard, Charles G. Miller, D. Craig CA Aortic Valve Operative Outcomes M TI Early and 1-year outcomes of aortic root surgery in patients with Marfan syndrome: A prospective, multicenter, comparative study SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID VALVE-SPARING OPERATION; ASCENDING AORTA; REPLACEMENT; REGURGITATION; GUIDELINES; MORBIDITY; MORTALITY; ANEURYSM AB Objective: To compare the 1-year results after aortic valve-sparing (AVS) or valve-replacing (AVR) aortic root replacement from a prospective, international registry of 316 patients with Marfan syndrome (MFS). Methods: Patients underwent AVS (n = 239, 76%) or AVR (n = 77, 24%) aortic root replacement at 19 participating centers from 2005 to 2010. One-year follow-up data were complete for 312 patients (99%), with imaging findings available for 293 (94%). The time-to-events were compared between groups using Kaplan-Meier curves and Cox proportional hazards models. Results: Two patients (0.6%)-1 in each group-died within 30 days. No significant differences were found in early major adverse valve-related events (MAVRE; P = .6). Two AVS patients required early reoperation for coronary artery complications. The 1-year survival rates were similar in the AVR (97%) and AVS (98%) groups; the procedure type was not significantly associated with any valve-related events. At 1 year and beyond, aortic regurgitation of at least moderate severity (>= 2+) was present in 16 patients in the AVS group (7%) but in no patients in the AVR group (P = .02). One AVS patient required late AVR. Conclusions: AVS aortic root replacement was not associated with greater 30-day mortality or morbidity rates than AVR root replacement. At 1 year, no differences were found in survival, valve- related morbidity, or MAVRE between the AVS and AVR groups. Of concern, 7% of AVS patients developed grade >= 2+ aortic regurgitation, emphasizing the importance of 5 to 10 years of follow-up to learn the long-term durability of AVS versus AVR root replacement in patients with MFS. C1 [Coselli, Joseph S.; Volguina, Irina V.; LeMaire, Scott A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, Houston, TX 77584 USA. [Coselli, Joseph S.; Volguina, Irina V.; LeMaire, Scott A.] Texas Heart Inst, Dept Cardiovasc Surg, Houston, TX 77025 USA. [Sundt, Thoralf M.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. [Connolly, Heidi M.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Stephens, Elizabeth H.; Miller, D. Craig] Stanford Univ, Sch Med, Dept Cardiothorac Surg, Stanford, CA 94305 USA. [Schaff, Hartzell V.] Mayo Clin, Dept Surg, Div Cardiovasc Surg, Rochester, MN USA. [Milewicz, Dianna M.] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Div Med Genet, Houston, TX 77030 USA. [Vricella, Luca A.] Johns Hopkins Univ Hosp, Dept Surg, Div Cardiac Surg, Baltimore, MD 21287 USA. [Dietz, Harry C.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. [Minard, Charles G.] Baylor Coll Med, Dan L Duncan Inst Clin & Translat Res, Houston, TX 77584 USA. RP Volguina, IV (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Div Cardiothorac Surg, One Baylor Plaza,BCM 390, Houston, TX 77584 USA. EM volguina@bcm.edu OI Schaff, Hartzell/0000-0003-0994-027X FU National Marfan Foundation; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex; Vascutek Ltd, St Jude Medical, Inc; Macquet Cardiovascular/Getinge Group; Dan L. Duncan Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Tex FX The present study was sponsored by the National Marfan Foundation and Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Tex. The National Marfan Foundation received unrestricted support from Vascutek Ltd, St Jude Medical, Inc, and the Macquet Cardiovascular/Getinge Group. Dr Minard is supported by the Dan L. Duncan Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Tex. NR 20 TC 20 Z9 21 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 2014 VL 147 IS 6 BP 1758 EP 1766 DI 10.1016/j.jtcvs.2014.02.021 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA AH9HF UT WOS:000336452000015 PM 24655904 ER PT J AU Antczak, C Trinh, VQ Sood, A Ravi, P Roghmann, F Trudeau, V Chang, SL Karakiewicz, PI Kibel, AS Krishna, N Nguyen, PL Saad, F Sammon, JD Sukumar, S Zorn, KC Sun, M Trinh, QD AF Antczak, Carina Trinh, Vincent Q. Sood, Akshay Ravi, Praful Roghmann, Florian Trudeau, Vincent Chang, Steven L. Karakiewicz, Pierre I. Kibel, Adam S. Krishna, Nandita Nguyen, Paul L. Saad, Fred Sammon, Jesse D. Sukumar, Shyam Zorn, Kevin C. Sun, Maxine Trinh, Quoc-Dien TI The Health Care Burden of Skeletal Related Events in Patients with Renal Cell Carcinoma and Bone Metastasis SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma, renal cell; bone and bones; neoplasm metastasis; hospital charges ID ZOLEDRONIC ACID; PROSTATE-CANCER; UNITED-STATES; SURVIVAL; COMPLICATIONS; SECONDARY; PATTERNS; THERAPY; DISEASE AB Purpose: We examined temporal trends in skeletal related events and associated charges in patients with renal cell carcinoma metastatic to bone. We also identified patient and hospital characteristics associated with skeletal related events and related mortality. Materials and Methods: Using the Nationwide Inpatient Sample we abstracted data on patients with renal cell carcinoma who were diagnosed with concomitant bone metastasis between 1998 and 2010. Patients who experienced a skeletal related event were identified and hospital charges were calculated. Multivariate regression models fitted with generalized estimating equations were used to examine predictors of skeletal related events and related in-hospital mortality. Results: Between 1998 and 2010 a weighted estimate of 144,889 renal cell carcinoma hospital visits of patients with bone metastasis was identified in the Nationwide Inpatient Sample, of which 20.8% involved a skeletal related event. In these cases from 1998 to 2010 the inflation adjusted mean yearly costs associated with hospital admission increased by 207% in 2013 United States dollars (estimated annual percent change 8.94%, p < 0.001). Conversely, the rates of skeletal related events and skeletal related event associated mortality decreased significantly (estimated annual percent change -1.11% and -2.9%, respectively, each p < 0.001). Conclusions: The prevalence and in-hospital mortality of skeletal related event associated hospitalization for metastatic renal cell carcinoma is decreasing but such charges to health care in the United States are increasing at an alarming rate. These findings highlight the need for cost-effective treatment strategies to prevent or treat these morbid complications. C1 [Antczak, Carina; Trinh, Vincent Q.; Roghmann, Florian; Trudeau, Vincent; Karakiewicz, Pierre I.; Zorn, Kevin C.; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Saad, Fred] Univ Montreal, Ctr Hlth, Div Urol, Montreal, PQ, Canada. [Sood, Akshay; Ravi, Praful; Sammon, Jesse D.] Vattikuti Urol Inst, Henry Ford Hlth Syst, Detroit, MI USA. [Roghmann, Florian] Ruhr Univ Bochum, Marienhosp, Dept Urol, Herne, Germany. [Sood, Akshay; Chang, Steven L.; Kibel, Adam S.; Krishna, Nandita; Trinh, Quoc-Dien] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Div Urol Surg, Boston, MA 02115 USA. [Sood, Akshay; Chang, Steven L.; Kibel, Adam S.; Krishna, Nandita; Trinh, Quoc-Dien] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. [Sukumar, Shyam] Univ Minnesota, Dept Urol, Minneapolis, MN USA. RP Antczak, C (reprint author), 1058 St Denis, Montreal, PQ H2X 3J4, Canada. EM carina.antczak@gmail.com NR 20 TC 4 Z9 4 U1 1 U2 3 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 JUN PY 2014 VL 191 IS 6 BP 1678 EP 1684 DI 10.1016/j.juro.2013.12.042 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AI0IS UT WOS:000336531100010 PM 24384157 ER PT J AU Gray, PJ Fedewa, SA Shipley, WU Efstathiou, JA Lin, CC Zietman, AL Virgo, KS AF Gray, P. J. Fedewa, S. A. Shipley, W. U. Efstathiou, J. A. Lin, C. C. Zietman, A. L. Virgo, K. S. TI Re: Use of Potentially Curative Therapies for Muscle-Invasive Bladder Cancer in the United States: Results from the National Cancer Data Base Editorial Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 [Gray, P. J.; Fedewa, S. A.; Shipley, W. U.; Efstathiou, J. A.; Lin, C. C.; Zietman, A. L.; Virgo, K. S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gray, PJ (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD JUN PY 2014 VL 191 IS 6 BP 1731 EP 1732 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA AI0IS UT WOS:000336531100023 ER PT J AU Saunders, RS Fernandes-Taylor, S Kind, AJH Engelbert, TL Greenberg, CC Smith, MA Matsumura, JS Kent, KC AF Saunders, Richard S. Fernandes-Taylor, Sara Kind, Amy J. H. Engelbert, Travis L. Greenberg, Caprice C. Smith, Maureen A. Matsumura, Jon S. Kent, K. Craig TI Rehospitalization to primary versus different facilities following abdominal aortic aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RURAL PATIENTS; SURGERY; VOLUME; CARE; REGIONALIZATION; READMISSIONS; HOSPITALS; MORTALITY; RESECTION; FAILURE AB Objective: Reducing readmissions represents a unique opportunity to improve care and reduce health care costs and is the focus of major payers. A large number of surgical patients are readmitted to hospitals other than where the primary surgery was performed, resulting in clinical decisions that do not incorporate the primary surgeon and potentially alter outcomes. This study characterizes readmission to primary vs different hospitals after abdominal aortic aneurysm (AAA) repair and examines the implications with regard to mortality and cost. Methods: Patients who underwent open or endovascular aneurysm repair for AAA were identified from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse, a random 5% national sample of Medicare beneficiaries from 2005 to 2009. Outcomes for patients who underwent AAA repair and were readmitted within 30 days of initial discharge were compared based on readmission location (primary vs different hospital). Results: A total of 885 patients underwent AAA repair and were readmitted within 30 days. Of these, 626 (70.7%) returned to the primary facility, and 259 (29.3%) returned to a different facility. Greater distance from patient residence to the primary hospital was the strongest predictor of readmission to a different facility. Patients living 50 to 100 miles from the primary hospital were more likely to be readmitted to a different hospital compared with patients living <10 miles away (odds ratio, 8.50; P < .001). Patients with diagnoses directly related to the surgery (eg, wound infection) were more likely to be readmitted to the primary hospital, whereas medical diagnoses (eg, pneumonia and congestive heart failure) were more likely to be treated at a different hospital. There was no statistically significant difference in mortality between patients readmitted to a different or the primary hospital. Median total 30-day payments were significantly lower at different vs primary hospitals (primary, $11,978 vs different, $11,168; P = .04). Conclusions: Readmission to a different facility after AAA repair is common and occurs more frequently than for the overall Medicare population. Patients travelling a greater distance for AAA repair are more likely to return to different vs the primary hospital when further care is required. For AAA repair, quality healthcare may be achieved at marginally lower cost and with greater patient convenience for selected readmissions at hospitals other than where the initial procedure was performed. C1 [Saunders, Richard S.; Fernandes-Taylor, Sara; Engelbert, Travis L.; Greenberg, Caprice C.; Matsumura, Jon S.; Kent, K. Craig] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Surg Outcomes Res Program WiSOR, Dept Surg, Madison, WI USA. [Kind, Amy J. H.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Div Geriatr, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA. [Kind, Amy J. H.] William S Middleton Hosp, GRECC, US Dept Vet Affairs, Madison, WI USA. RP Kent, KC (reprint author), H4 710 Clin Sci Ctr, 600 Highland Ave, Madison, WI 53792 USA. EM kent@surgery.wisc.edu FU Health Innovation Program; University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program; Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR) through the National Center for Advancing Translational Sciences (NCATS) [UL1TR000427] FX This project was supported in part by the Health Innovation Program, the University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program, and the Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (UW ICTR) through the National Center for Advancing Translational Sciences (NCATS), grant UL1TR000427. NR 27 TC 12 Z9 12 U1 0 U2 3 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 JUN PY 2014 VL 59 IS 6 BP 1502 EP + DI 10.1016/j.jvs.2013.12.015 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AH8DH UT WOS:000336363800004 PM 24491237 ER PT J AU Lombardi, JV Cambria, RP Nienaber, CA Chiesa, R Mossop, P Haulon, S Zhou, Q Jia, FY AF Lombardi, Joseph V. Cambria, Richard P. Nienaber, Christoph A. Chiesa, Roberto Mossop, Peter Haulon, Stephan Zhou, Qing Jia, Feiyi CA STABLE Investigators TI Aortic remodeling after endovascular treatment of complicated type B aortic dissection with the use of a composite device design SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 29-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg ID STENT-GRAFT PLACEMENT; INTERNATIONAL REGISTRY; THORACIC AORTA; FALSE LUMEN; REPAIR; MANAGEMENT; IRAD; MULTICENTER; INSIGHTS; OUTCOMES AB Objective: The purpose of this study is to report updated clinical and aortic remodeling results from the Study for the Treatment of complicated Type B Aortic Dissection using Endoluminal repair (STABLE) trial, a prospective, multicenter study evaluating safety and effectiveness of a pathology-specific endovascular system (proximal stent graft and distal bare metal stent) for the treatment of complicated type B aortic dissection. Methods: All 86 enrolled patients (mean age, 59 years; 73.3% men) were treated within 90 days of symptom onset (55 with acute dissections and 31 with nonacute dissections). Inclusion criteria were branch vessel obstruction/compromise, impending rupture as evidenced by periaortic effusion/hematoma, resistant hypertension, persistent pain/symptoms, or aortic growth >= 5 mm within 3 months (or transaortic diameter >= 40 mm). Remodeling of the dissected aorta, including thrombosis of the false lumen and changes in the true lumen, false lumen, and transaortic diameter, were assessed in patients with available computed tomographic imaging through 2 years. Results: The 30-day mortality rate was 4.7% (4/86) in the overall patient group (5.5% in acute patients and 3.2% in nonacute patients). Freedom from all-cause mortality was 88.3% at 1 year and 84.7% at 2 years (no significant difference between acute and nonacute patients). From baseline to 2 years, the true lumen diameter increased significantly in the descending thoracic aorta and the more distal abdominal aorta, along with a decrease in the false lumen diameter in both aortic segments. A majority of patients had either a stable or shrinking transaortic diameter in the thoracic (80.3% at 1 year and 73.9% at 2 years) or abdominal aorta (79.1% at 1 year and 66.7% at 2 years). Transaortic growth (>5 mm) occurred predominantly in acute dissections. Consistently, a shorter time from symptom onset to treatment was found to predict transaortic growth in the abdominal aorta (P = .03). Conclusions: Endovascular repair of complicated type B aortic dissection with the use of a composite construct demonstrates favorable early clinical outcomes and aortic remodeling. However, patients treated in the acute setting may be prone to aortic growth and may require close observation. Follow-up through 5 years is ongoing. C1 [Lombardi, Joseph V.] Cooper Univ Hosp, Dept Surg, Camden, NJ 08103 USA. [Cambria, Richard P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Nienaber, Christoph A.] Univ Hosp Rostock, Dept Med, Rostock, Germany. [Chiesa, Roberto] Hosp San Raffaele, Dept Surg, I-20132 Milan, Italy. [Mossop, Peter] St Vincents Hosp, Dept Radiol, Melbourne, Vic, Australia. [Haulon, Stephan] CHRU Lille, Hosp Cardiol, Dept Surg, F-59037 Lille, France. [Zhou, Qing; Jia, Feiyi] MED Inst, W Lafayette, IN USA. RP Lombardi, JV (reprint author), Cooper Univ Hosp, Div Vasc & Endovasc Surg, Three Cooper Plaza,Ste 411, Camden, NJ 08103 USA. EM lombardi-joseph@CooperHealth.edu NR 26 TC 18 Z9 21 U1 1 U2 2 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 JUN PY 2014 VL 59 IS 6 BP 1544 EP 1554 DI 10.1016/j.jvs.2013.12.038 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AH8DH UT WOS:000336363800010 PM 24560244 ER PT J AU Kougias, P Sharath, S Barshes, NR Lowery, B Garcia, A Pak, T Bechara, CF Pisimisis, G AF Kougias, Panos Sharath, Sherene Barshes, Neal R. Lowery, Briauna Garcia, Andrea Pak, Taemee Bechara, Carlos F. Pisimisis, George TI Impact of cumulative intravascular contrast exposure on renal function in patients with occlusive and aneurysmal vascular disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 38th Annual Spring Meeting of the Peripheral-Vascular-Surgery-Society CY MAY 29, 2013 CL San Francisco, CA SP Peripheral Vasc Surg Soc ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; RISK-FACTORS; INDUCED NEPHROPATHY; PROXIMAL FIXATION; REPAIR; DYSFUNCTION; CONSEQUENCES; TERM AB Objective: Patients with occlusive or aneurysmal vascular disease are repeatedly exposed to intravascular (IV) contrast for diagnostic or therapeutic purposes. We sought to determine the long-term impact of cumulative iodinated IV contrast exposure (CIVCE) on renal function; the latter was defined by means of National Kidney Foundation (NKF) criteria. Methods: We performed a longitudinal study of consecutive patients without renal insufficiency at baseline (NFK stage I or II) who underwent interventions for arterial occlusive or aneurysmal disease. We collected detailed data on any IV iodinated contrast exposure (including diagnostic or therapeutic angiography, cardiac catheterization, IV pyelography, computed tomography with IV contrast, computed tomographic angiography); medication exposure throughout the observation period; comorbidities; and demographics. The primary end point was the development of renal failure (RF) (defined as NFK stage 4 or 5). Analysis was performed with the use of a shared frailty model with clustering at the patient level. Results: Patients (n = 1274) had a mean follow-up of 5.8 (range, 2.2-14) years. In the multivariate model with RF as the dependent variable and after adjusting for the statistically significant covariates of baseline renal function (hazard ratio [HR], 0.95; P < .001), diabetes (HR, 1.8; P = .007), use of an angiotensin-converting enzyme inhibitor (HR, 0.63; P = .03), use of antiplatelets (HR, 0.5; P = .01), cumulative number of open vascular operations performed (HR, 1.2; P = .001), and congestive heart failure (HR, 3.2; P < .001), CIVCE remained an independent predictor for RF development (HR, 1.1; P < .001). In the multivariate survival analysis model and after adjusting for the statistically significant covariates of perioperative myocardial infarction (HR, 3.9; P < .001), age at entry in the cohort (HR, 1.05; P = .035), total number of open operations (HR, 1.51; P < .001), and serum albumin (HR, 0.47; P < .001), CIVCE was an independent predictor of death (HR, 1.07; P < .001). Conclusions: Cumulative IV contrast exposure is an independent predictor of RF and death in patients with occlusive and aneurysmal vascular disease. C1 [Kougias, Panos; Sharath, Sherene; Barshes, Neal R.; Lowery, Briauna; Bechara, Carlos F.; Pisimisis, George] Michael E DeBakey VA Med Ctr, Dept Surg, Houston, TX USA. [Kougias, Panos; Barshes, Neal R.; Garcia, Andrea; Pak, Taemee; Bechara, Carlos F.; Pisimisis, George] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. RP Kougias, P (reprint author), Houston VAMC, Dept Surg, 2002 Holcombe Blvd OCL 112, Houston, TX 77030 USA. EM pkougias@bcm.edu NR 17 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 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2014 VL 59 IS 6 BP 1644 EP 1650 DI 10.1016/j.jvs.2013.12.039 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA AH8DH UT WOS:000336363800025 PM 24560864 ER PT J AU Lee, LC Ge, L Zhang, ZH Pease, M Nikolic, SD Mishra, R Ratcliffe, MB Guccione, JM AF Lee, Lik Chuan Ge, Liang Zhang, Zhihong Pease, Matthew Nikolic, Serjan D. Mishra, Rakesh Ratcliffe, Mark B. Guccione, Julius M. TI Patient-specific finite element modeling of the Cardiokinetix Parachute(A (R)) device: effects on left ventricular wall stress and function SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE Myocardial infarction; Remodeling; Finite element method; Surgical ventricular restoration ID CHRONIC HEART-FAILURE; MYOCARDIAL-INFARCTION; MRI; RESTORATION; MECHANICS; ANEURYSM AB The Parachute(A (R)) (Cardiokinetix, Inc., Menlo Park, California) is a catheter-based device intended to reverse left ventricular (LV) remodeling after antero-apical myocardial infarction. When deployed, the device partitions the LV into upper and lower chambers. To simulate its mechanical effects, we created a finite element LV model based on computed tomography (CT) images from a patient before and 6 months after Parachute(A (R)) implantation. Acute mechanical effects were determined by in silico device implantation (VIRTUAL-Parachute). Chronic effects of the device were determined by adjusting the diastolic and systolic material parameters to better match the 6-month post-implantation CT data and LV pressure data at end-diastole (ED) (POST-OP). Regional myofiber stress and pump function were calculated in each case. The principal finding is that VIRTUAL-Parachute was associated with a 61.2 % reduction in the lower chamber myofiber stress at ED. The POST-OP model was associated with a decrease in LV diastolic stiffness and a larger reduction in myofiber stress at the upper (27.1 %) and lower chamber (78.4 %) at ED. Myofiber stress at end-systole and stroke volume was little changed in the POST-OP case. These results suggest that the primary mechanism of Parachute(A (R)) is a reduction in ED myofiber stress, which may reverse eccentric post-infarct LV hypertrophy. C1 [Lee, Lik Chuan; Ge, Liang; Ratcliffe, Mark B.; Guccione, Julius M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Lee, Lik Chuan; Ge, Liang; Ratcliffe, Mark B.; Guccione, Julius M.] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. [Lee, Lik Chuan; Ge, Liang; Zhang, Zhihong; Mishra, Rakesh; Ratcliffe, Mark B.; Guccione, Julius M.] San Francisco VA Med Ctr, Div Surg Serv 112, San Francisco, CA 94121 USA. [Pease, Matthew; Nikolic, Serjan D.] Cardiokinetix Inc, Menlo Pk, CA USA. [Mishra, Rakesh] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Ratcliffe, MB (reprint author), San Francisco VA Med Ctr, Div Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. EM mark.ratcliffe@va.gov FU NIH [R01-HL-084431, R01-HL-077921, R01-HL-118627] FX This study was supported by an unrestricted gift from Cardiokinetix and NIH grants R01-HL-084431 (Dr. Ratcliffe), R01-HL-077921 and R01-HL-118627 (Dr. Guccione). NR 23 TC 15 Z9 17 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0140-0118 EI 1741-0444 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD JUN PY 2014 VL 52 IS 6 BP 557 EP 566 DI 10.1007/s11517-014-1159-5 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA AH8HO UT WOS:000336378200005 PM 24793158 ER PT J AU Hess, AT Jacobson, SW Jacobson, JL Molteno, CD van der Kouwe, AJW Meintjes, EM AF Hess, Aaron T. Jacobson, Sandra W. Jacobson, Joseph L. Molteno, Christopher D. van der Kouwe, Andre J. W. Meintjes, Ernesta M. TI A comparison of spectral quality in magnetic resonance spectroscopy data acquired with and without a novel EPI-navigated PRESS sequence in school-aged children with fetal alcohol spectrum disorders SO METABOLIC BRAIN DISEASE LA English DT Article DE Magnetic resonance spectroscopy; Motion correction; B0 correction; EPI navigator; Fetal alcohol spectrum disorders; South Africa ID RISK-FACTORS; SIGNAL LOSS; EXPOSURE; MOTION; CAPE; FEATURES; WOMEN; FMRI; IQ AB Single voxel spectroscopy (SVS) can generate useful information regarding metabolite concentrations provided that the MR signal can be averaged over several minutes during which the subject remains stationary. This requirement can be particularly challenging for children who cannot otherwise be scanned without sedation. To address this problem we developed an EPI volume navigated (vNav) SVS PRESS sequence, which applies real-time head pose (location and orientation), frequency, and first-order B0 shim adjustments. A water-independent preprocessing algorithm removes residual frequency and phase shifts resulting from within-TR movements. We compare results and performance of the standard and vNav PRESS sequences in a sample of 9- to 10-year-olds from a South African cohort of children with fetal alcohol spectrum disorders (FASD) and healthy controls. Magnetic resonance spectroscopy (MRS) data in the deep cerebellar nuclei were initially acquired with the standard PRESS sequence. The children were re-scanned 1 year later with the vNav PRESS sequence. Good quality data were acquired in 73 % using the vNav PRESS sequence, compared to only 50 % for the standard PRESS sequence. Additionally, tighter linewidths and smaller variances in the measured concentrations were observed. These findings confirm previous reports demonstrating the efficacy of our innovative vNav sequence with healthy volunteers and young children with HIV and expand its application to a school-aged population with FASD-disorders often associated with attention problems and hyperactivity. This study provides the most direct evidence to date regarding degree to which these new methods can improve data quality in research studies employing MRS. C1 [Hess, Aaron T.; Meintjes, Ernesta M.] Univ Cape Town, Fac Hlth Sci, MRC UCT Med Imaging Res Unit, ZA-7925 Cape Town, South Africa. [Hess, Aaron T.; Jacobson, Sandra W.; Jacobson, Joseph L.; Meintjes, Ernesta M.] Univ Cape Town, Dept Human Biol, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. [Hess, Aaron T.] Univ Oxford, Ctr Clin Magnet Resonance Res, Oxford, England. [Jacobson, Sandra W.; Jacobson, Joseph L.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA. [Jacobson, Sandra W.; Jacobson, Joseph L.; Molteno, Christopher D.] Univ Cape Town, Dept Psychiat & Mental Hlth, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. [van der Kouwe, Andre J. W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [van der Kouwe, Andre J. W.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Meintjes, EM (reprint author), Univ Cape Town, Dept Human Biol, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. EM sandra.jacobson@wayne.edu; ernesta.meintjes@gmail.com FU South African Research Chairs Initiative of the Department of Science and Technology; National Research Foundation of South Africa; Medical Research Council of South Africa; NIH/National Institute on Alcohol Abuse and Alcoholism [R21AA017410, R01AA016781, R01 AA09524, U01 AA014790, U24 AA014815]; University of Cape Town; Wayne State University; Joseph Young, Sr., Fund from the State of Michigan; Collaborative Initiative on Fetal Alcohol Spectrum Disorders [U01, U24] FX This research was funded by grants from the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa, Medical Research Council of South Africa, NIH/National Institute on Alcohol Abuse and Alcoholism (R21AA017410, R01AA016781, R01 AA09524, U01 AA014790, and U24 AA014815) and the University of Cape Town, Wayne State University, and Joseph Young, Sr., Fund from the State of Michigan. We thank Siemens, Bruce Spottiswoode, Ph.D., the CUBIC radiographers Marie-Louise de Villiers and Nailah Maroof, Lindie du Plessis for assistance with LCModel analyses, Mathematician/Physicist M. Dylan Tisdall, our UCT and WSU research staff Maggie September, Nicolette Hamman, Mariska Pienaar, Emma Makin, and Neil Dodge. We also thank the dysmorphologists, H. Eugene Hoyme, Luther K. Robinson, and Nathanial Khaole, who conducted the dysmorphology diagnostic examinations of the children for FASD, funded by U01 and U24 grants from the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (listed above). We also greatly appreciate the participation of the mothers and children in the longitudinal study. NR 33 TC 2 Z9 2 U1 1 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 EI 1573-7365 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD JUN PY 2014 VL 29 IS 2 SI SI BP 323 EP 332 DI 10.1007/s11011-014-9487-6 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA AH7SU UT WOS:000336335200012 PM 24488204 ER PT J AU Heatwole, C Bode, R Johnson, N Dekdebrun, J Dilek, N Heatwole, M Hilbert, JE Luebbe, E Martens, W Mcdermott, MP Rothrock, N Thornton, C Vickrey, BG Victorson, D Moxley, R AF Heatwole, Chad Bode, Rita Johnson, Nicholas Dekdebrun, Jeanne Dilek, Nuran Heatwole, Mark Hilbert, James E. Luebbe, Elizabeth Martens, William Mcdermott, Michael P. Rothrock, Nan Thornton, Charles Vickrey, Barbara G. Victorson, David Moxley, Richard, III TI MYOTONIC DYSTROPHY HEALTH INDEX: INITIAL EVALUATION OF A DISEASE-SPECIFIC OUTCOME MEASURE SO MUSCLE & NERVE LA English DT Article DE pain management; pain assessment; myotonic dystrophy type 1; facioscapulohumeral muscular dystrophy; rehabilitation ID PATIENT-REPORTED OUTCOMES; QUALITY-OF-LIFE; MUSCULAR-DYSTROPHY; DRUG DEVELOPMENT; CTG REPEAT; PERSPECTIVE; VALIDITY; TYPE-1; TRIALS; GENE AB Introduction: We examined the effects of pain site and intensity on function in patients with myotonic dystrophy type 1 (DM1) and facioscapulohumeral muscular dystrophy (FSHD) and chronic pain. Methods: Questionnaires assessing pain sites, pain extent (number of sites), pain intensity, and pain interference were completed by 182 individuals with DM1 (43%) or FSHD (57%) and chronic pain. Results: There was a positive association between pain extent and intensity with pain interference, and a negative association with psychological functioning in both DM1 and FSHD. Pain intensity at specific sites had differential impact beyond the effects of pain intensity alone. Head pain intensity independently affected psychological functioning, whereas leg, foot, hip, and knee pain contributed independently to the prediction of pain interference. Conclusions: Pain site and intensity differentially modulates the effect of chronic pain on function in DM1 and FSHD patients. Researchers and clinicians should consider these factors when assessing and treating pain. Muscle Nerve 49: 900-905, 2014 C1 [Heatwole, Chad; Dekdebrun, Jeanne; Dilek, Nuran; Hilbert, James E.; Luebbe, Elizabeth; Martens, William; Mcdermott, Michael P.; Thornton, Charles; Moxley, Richard, III] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA. [Bode, Rita] Psychometr Consultant, Chicago, IL USA. [Johnson, Nicholas] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Mcdermott, Michael P.] Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. [Rothrock, Nan; Victorson, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Vickrey, Barbara G.] Univ Calif Los Angeles, Med Ctr, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Vickrey, Barbara G.] Greater Los Angeles VA HealthCare Syst, Los Angeles, CA USA. RP Heatwole, C (reprint author), Univ Rochester, Med Ctr, Dept Neurol, 601 Elmwood Ave,Box 673, Rochester, NY 14642 USA. EM chad_heatwole@urmc.rochester.edu FU National Institute of Arthritis and Musculoskeletal and Skin Disorders [1K23AR055947]; Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center [NINDS U54NS48843]; Muscular Dystrophy Association; Saunders Family Fund; University of Rochester CTSA award from the National Center for Research Resources [UL1 RR024160]; National Center for Advancing Translational Sciences of the National Institutes of Health FX Partial support for this research was provided by the National Institute of Arthritis and Musculoskeletal and Skin Disorders (1K23AR055947), the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center (NINDS U54NS48843), the Muscular Dystrophy Association, and the Saunders Family Fund. The project described in this publication was also supported by the University of Rochester CTSA award number UL1 RR024160 from the National Center for Research Resources and the National Center for Advancing Translational Sciences of the 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. Additional information regarding the MDHI is available at the Neuromuscular Institute of Quality-of-Life Studies and Outcome Measure Development website www.QOLINSTITUTE.com and MDHI licensing opportunities can be reviewed at: www.urmc.rochester.edu/techtransfer. NR 27 TC 5 Z9 5 U1 2 U2 7 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 JUN PY 2014 VL 49 IS 6 BP 906 EP 914 DI 10.1002/mus.24079 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AH2MA UT WOS:000335954400016 PM 24142420 ER PT J AU Peng, ZC Zhang, NH Chandra, D Homanics, GE Olsen, RW Houser, CR AF Peng, Zechun Zhang, Nianhui Chandra, Dave Homanics, Gregg E. Olsen, Richard W. Houser, Carolyn R. TI Altered Localization of the delta Subunit of the GABA(A) Receptor in the Thalamus of alpha 4 Subunit Knockout Mice SO NEUROCHEMICAL RESEARCH LA English DT Article DE Immunohistochemistry; Non-synaptic GABA receptors; Plasticity; Receptor trafficking; Tonic inhibition; Ventrobasal nucleus ID TEMPORAL-LOBE EPILEPSY; AMINOBUTYRIC ACID(A) RECEPTORS; INTERMITTENT ETHANOL TREATMENT; CEREBELLAR GRANULE CELLS; ADULT-RAT BRAIN; TONIC INHIBITION; PHARMACOLOGICAL CHARACTERIZATION; IMMUNOCYTOCHEMICAL DISTRIBUTION; ENDOPLASMIC-RETICULUM; BEHAVIORAL-RESPONSES AB The alpha 4 subunit of the GABA(A) receptor (GABA(A)R) is highly expressed in the thalamus where receptors containing the alpha 4 and delta subunits are major mediators of tonic inhibition. The alpha 4 subunit also exhibits considerable plasticity in a number of physiological and pathological conditions, raising questions about the expression of remaining GABA(A)R subunits when the alpha 4 subunit is absent. Immunohistochemical studies of an alpha 4 subunit knockout (KO) mouse revealed a substantial decrease in delta subunit expression in the ventrobasal nucleus of the thalamus as well as other forebrain regions where the alpha 4 subunit is normally expressed. In contrast, several subunits associated primarily with phasic inhibition, including the alpha 1 and gamma 2 subunits, were moderately increased. Intracellular localization of the delta subunit was also altered. While delta subunit labeling was decreased within the neuropil, some labeling remained in the cell bodies of many neurons in the ventrobasal nucleus. Confocal microscopy demonstrated co-localization of this labeling with an endoplasmic reticulum marker, and electron microscopy demonstrated increased immunogold labeling near the endoplasmic reticulum in the alpha 4 KO mouse. These results emphasize the strong partnership of the delta and alpha 4 subunit in the thalamus and suggest that the alpha 4 subunit of the GABA(A)R plays a critical role in trafficking of the delta subunit to the neuronal surface. The findings also suggest that previously observed reductions in tonic inhibition in the alpha 4 subunit KO mouse are likely to be related to alterations in delta subunit expression, in addition to loss of the alpha 4 subunit. C1 [Peng, Zechun; Zhang, Nianhui; Houser, Carolyn R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Chandra, Dave; Homanics, Gregg E.] Univ Pittsburgh, Dept Anesthesiol & Pharmacol & Chem Biol, Pittsburgh, PA USA. [Olsen, Richard W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Houser, Carolyn R.] VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, CHS 73-235, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu FU National Institutes of Health [NS075245, AA14022, AA13004, AA007680]; Veterans Affairs Medical Research Funds FX We thank Drs. Jean-Marc Fritschy and Werner Sieghart for generously sharing their GABAAR subunit-specific antisera that have made these studies possible. We also thank Christine Huang and Yliana Cetina for outstanding assistance with tissue processing and figure preparation. This work was supported by National Institutes of Health Grants NS075245 (CRH), AA14022 and AA13004 (GEH), AA007680 (RWO), and Veterans Affairs Medical Research Funds (CRH). NR 72 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 EI 1573-6903 J9 NEUROCHEM RES JI Neurochem. Res. PD JUN PY 2014 VL 39 IS 6 SI SI BP 1104 EP 1117 DI 10.1007/s11064-013-1202-1 PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA AH6WJ UT WOS:000336272500013 PM 24352815 ER PT J AU Kim, WH Singh, V Chung, MK Hinrichs, C Pachauri, D Okonkwo, OC Johnson, SC AF Kim, Won Hwa Singh, Vikas Chung, Moo K. Hinrichs, Chris Pachauri, Deepti Okonkwo, Ozioma C. Johnson, Sterling C. CA Alzheimer's Dis Neuroimaging Initi TI Multi-resolutional shape features via non-Euclidean wavelets: Applications to statistical analysis of cortical thickness SO NEUROIMAGE LA English DT Article DE Non-Euclidean wavelet; Multi-resolution analysis; Graph wavelets; Shape analysis; Cortical thickness discrimination; Alzheimer's disease ID ALZHEIMERS-DISEASE; SURFACE-AREA; GRAY-MATTER; HEAT KERNEL; CHILDREN; CT; ADOLESCENTS; MRI; REPRESENTATION; SCHIZOPHRENIA AB Statistical analysis on arbitrary surface meshes such as the cortical surface is an important approach to understanding brain diseases such as Alzheimer's disease (AD). Surface analysis may be able to identify specific cortical patterns that relate to certain disease characteristics or exhibit differences between groups. Our goal in this paper is to make group analysis of signals on surfaces more sensitive. To do this, we derive multi-scale shape descriptors that characterize the signal around each mesh vertex, i.e., its local context, at varying levels of resolution. In order to define such a shape descriptor, we make use of recent results from harmonic analysis that extend traditional continuous wavelet theory from the Euclidean to a non-Euclidean setting (i.e., a graph, mesh or network). Using this descriptor, we conduct experiments on two different datasets, the Alzheimer's Disease NeuroImaging Initiative (ADNI) data and images acquired at the Wisconsin Alzheimer's Disease Research Center (W-ADRC), focusing on individuals labeled as having Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy controls. In particular, we contrast traditional univariate methods with our multi-resolution approach which show increased sensitivity and improved statistical power to detect a group-level effects. We also provide an open source implementation. (C) 2014 Elsevier Inc. All rights reserved. C1 [Kim, Won Hwa; Singh, Vikas; Hinrichs, Chris; Pachauri, Deepti] Univ Wisconsin, Dept Comp Sci, Madison, WI 53706 USA. [Singh, Vikas; Chung, Moo K.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53705 USA. [Kim, Won Hwa; Singh, Vikas; Okonkwo, Ozioma C.; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [Okonkwo, Ozioma C.; Johnson, Sterling C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI 53792 USA. RP Kim, WH (reprint author), Univ Wisconsin, Dept Comp Sci, 1210 W Dayton St, Madison, WI 53706 USA. EM wonhwa@cs.wisc.edu; vsingh@biostat.wisc.edu OI Kim, Won Hwa/0000-0001-5393-0883; Johnson, Sterling/0000-0002-8501-545X FU NIH [R01AG040396, R01AG021155, P30 AG010129, K01 AG030514]; NSF [RI 1116584]; NSF CAREER award [1252725]; UW ADRC [P50 AG033514]; Wisconsin Partnership Program; UW ICTR [1UL1RR025011]; CIBM pre-doctoral fellowship via NLM grant [5T15LM007359]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research FX We provide a freely downloadable implementation of this framework at http://pages.cs.wisc.edu/-wonhwa/CTA_toolbox/. This research was supported by funding from NIH R01AG040396, NIH R01AG021155, NSF RI 1116584, NSF CAREER award 1252725, UW ADRC (P50 AG033514), the Wisconsin Partnership Program, UW ICTR (1UL1RR025011)and Chris Hinrichs was supported by a CIBM pre-doctoral fellowship via NLM grant 5T15LM007359. We appreciate N. Maritza Dowling, Jennifer Oh, Vamsi Ithapu, Joon H. Lee and Gun W. Park for their help in processing the data and/or the preparation of this manuscript.; Data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Mesa Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseininated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129 and K01 AG030514. NR 52 TC 11 Z9 11 U1 0 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2014 VL 93 BP 107 EP 123 DI 10.1016/j.neuroimage.2014.02.028 PN 1 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA AH7WW UT WOS:000336347100010 PM 24614060 ER PT J AU Portelius, E Holtta, M Soininen, H Bjerke, M Zetterberg, H Westerlund, A Herukka, SK Blennow, K Mattsson, N AF Portelius, Erik Holtta, Mikko Soininen, Hilkka Bjerke, Maria Zetterberg, Henrik Westerlund, Anni Herukka, Sanna-Kaisa Blennow, Kaj Mattsson, Niklas TI Altered Cerebrospinal Fluid Levels of Amyloid beta and Amyloid Precursor-Like Protein 1 Peptides in Down's Syndrome SO NEUROMOLECULAR MEDICINE LA English DT Article DE Down's syndrome; Amyloid beta; Amyloid precursor-like protein 1; Mass spectrometry; Cerebrospinal fluid ID ALZHEIMERS-DISEASE; BRAIN; BIOMARKER; CLEAVAGE; SYSTEM AB Down's syndrome (DS) patients develop early Alzheimer's disease pathology with abundant cortical amyloid plaques, likely due to overproduction of the amyloid precursor protein (APP), which subsequently leads to amyloid beta (A beta) aggregation. This is reflected in cerebrospinal fluid (CSF) levels of the 42-amino acid long A beta peptide (A beta 1-42), which are increased in young DS patients and decreases with age. However, it is unclear whether DS also affects other aspects of A beta metabolism, including production of shorter C- and N-terminal truncated A beta peptides, and production of peptides from the amyloid precursor-like protein 1 (APLP1), which is related to APP, and cleaved by the same enzymatic processing machinery. APLP1-derived peptides may be surrogate markers for A beta 1-42 production in the brain. Here, we used hybrid immunoaffinity-mass spectrometry and enzyme-linked immunosorbent assays to monitor several A beta and APLP1 peptides in CSF from DS patients (n = 12) and healthy controls (n = 20). CSF levels of A beta 1-42 and three endogenous peptides derived from APLP1 (APL1 beta 25, APL1 beta 27 and APL1 beta 28) were decreased in DS compared with controls, while a specific A beta peptide, A beta 1-28, was increased in a majority of the DS individuals. This study indicates that DS causes previously unknown specific alterations of APP and APLP1 metabolism. C1 [Portelius, Erik; Holtta, Mikko; Bjerke, Maria; Zetterberg, Henrik; Westerlund, Anni; Blennow, Kaj; Mattsson, Niklas] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden. [Soininen, Hilkka; Herukka, Sanna-Kaisa] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Soininen, Hilkka; Herukka, Sanna-Kaisa] Univ Eastern Finland, Inst Clin Med Neurol, Sch Med, Kuopio 70211, Finland. [Zetterberg, Henrik] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Mattsson, Niklas] Univ Calif San Francisco, San Francisco VA Med Ctr, CIND, San Francisco, CA USA. [Mattsson, Niklas] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Portelius, E (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Gothenburg, Sweden. EM erik.portelius@neuro.gu.se FU Swedish Research Council [14002, K2010-63P-21562-01-4, K2011-61X-20401-05-6]; Stiftelsen Gamla Tjanarinnor; Magn. Bergvalls Stiftelse; Gun och Bertil Stohnes Stiftelse; Swedish Brain Fund; Alzheimer Foundation, Sweden; Dementia Association, Sweden; Wenner-gren foundation; Strategic for UEF-BRAIN; JPND Project BIOMARKAPD; Goteborgs Lakaresallskap; Svenska Lakaresallskapet; Klinisk Biokemi i Norden; Carl-Bertil Laurells fond FX The study was supported by the Swedish Research Council (Project Nos. 14002, K2010-63P-21562-01-4, K2011-61X-20401-05-6), Stiftelsen Gamla Tjanarinnor, Magn. Bergvalls Stiftelse, Gun och Bertil Stohnes Stiftelse, the Swedish Brain Fund, the Alzheimer Foundation, Sweden, the Dementia Association, Sweden, Wenner-gren foundation, Strategic for UEF-BRAIN and the JPND Project BIOMARKAPD, Goteborgs Lakaresallskap, Svenska Lakaresallskapet, Klinisk Biokemi i Norden, Carl-Bertil Laurells fond. NR 26 TC 7 Z9 7 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 EI 1559-1174 J9 NEUROMOL MED JI Neuromol. Med. PD JUN PY 2014 VL 16 IS 2 BP 510 EP 516 DI 10.1007/s12017-014-8302-1 PG 7 WC Neurosciences SC Neurosciences & Neurology GA AH6EW UT WOS:000336224500022 PM 24740518 ER PT J AU Borsook, D Aasted, CM Burstein, R Becerra, L AF Borsook, David Aasted, Christopher M. Burstein, Rami Becerra, Lino TI Migraine Mistakes: Error Awareness SO NEUROSCIENTIST LA English DT Article DE headache; pain; insula; basal ganglia; neural networks ID MEDIAL PREFRONTAL CORTEX; BASAL GANGLIA; PREDICTION ERRORS; CINGULATE CORTEX; ORBITOFRONTAL CORTEX; REWARD PREDICTION; DOPAMINE NEURONS; BRAIN; ANXIETY; INSULA AB Error awareness or detection is the conscious and subconscious processing to evaluate physiological signals that are different from a baseline or homeostatic level. Migraine is a unique neurological disorder in which there are repeated attacks interspersed by attack-free periods. These attacks are dynamic and multidimensional in the sense that sensory, affective, autonomic, and cognitive functions are altered and these changes evolve differently before (pre-ictal), during (ictal), and immediately after (post-ictal) an attack. Thus migraine serves as a model disease to understand how the brain monitors and react to the presence of errors. C1 [Borsook, David; Aasted, Christopher M.; Becerra, Lino] Harvard Univ, Sch Med, Ctr Pain & Brain, Boston, MA USA. [Borsook, David; Aasted, Christopher M.; Becerra, Lino] Harvard Univ, Massachusetts Gen Hosp, Sch Med, PAIN Grp,Boston Childrens Hosp, Boston, MA USA. [Borsook, David; Aasted, Christopher M.; Becerra, Lino] Harvard Univ, Sch Med, McLean Hosp, Boston, MA USA. [Burstein, Rami] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Boston, MA USA. RP Borsook, D (reprint author), Boston Childrens Hosp, Ctr Pain & Brain, 9 Hope Ave,Box 26, Waltham, MA 02453 USA. EM dborsook@partners.org FU National Institute of Neurological Disorders and Stroke (NINDS) [R01 NS073997, R01 NS075018, K24 NS064050, R01 NS069847, R37 079778] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS) (R01 NS073997, R01 NS075018, and K24 NS064050) to DB, and R01 NS069847 and R37 079778 to RB. NR 93 TC 3 Z9 3 U1 0 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 EI 1089-4098 J9 NEUROSCIENTIST JI Neuroscientist PD JUN PY 2014 VL 20 IS 3 BP 291 EP 304 DI 10.1177/1073858413503711 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AH6TZ UT WOS:000336265200013 PM 24047609 ER PT J AU Kemmerly, T Vuong, C Kaunitz, JD AF Kemmerly, Thomas Vuong, Carolyn Kaunitz, Jonathan D. TI A Novel Phosphorus Repletion Strategy in a Patient With Duodenal Perforation SO NUTRITION IN CLINICAL PRACTICE LA English DT Article DE adult; nutrition; phosphates; duodenum; drug shortage; parenteral formulas/compounding; GI access; phosphorus; fluids-electrolytes/acid-base; enteral access; parenteral nutrition; enema; life cycle; minerals/trace elements ID SEVERE HYPOPHOSPHATEMIA; ENEMA; HYPERPHOSPHATEMIA; NUTRITION AB We describe a case in which a patient receiving parenteral nutrition (PN) developed hypophosphatemia. Due to lack of availability of parenteral phosphate supplements, we chose to restore phosphate using diluted hypertonic sodium phosphate enemas. Due to the recent shortages of parenteral minerals and vitamins, such an alternate means of repletion is of increasing importance. Diluted hypertonic sodium phosphate enemas are inexpensive, easy to administer, and effective since phosphate is readily absorbed across the rectal mucosa. We hope that through this type of repletion, life-threatening hypophosphatemia among patients receiving PN can be avoided. C1 [Kemmerly, Thomas] Cedars Sinai Med Residency Program, Los Angeles, CA USA. [Vuong, Carolyn] WLAVA Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Dept Med, Los Angeles, CA USA. [Vuong, Carolyn] WLAVA Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Dept Pharm, Los Angeles, CA USA. [Kaunitz, Jonathan D.] UCLA Sch Med, Dept Med, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] UCLA Sch Med, Dept Surg, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), UCLA Sch Med, West Los Angeles VAMC, Bldg 114,Room 217E, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [R01 DK054221] NR 17 TC 1 Z9 1 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0884-5336 EI 1941-2452 J9 NUTR CLIN PRACT JI Nutr. Clin. Pract. PD JUN PY 2014 VL 29 IS 3 BP 402 EP 405 DI 10.1177/0884533614529997 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA AH0FP UT WOS:000335794900020 PM 24743045 ER PT J AU Fox, E Mosse', YP Meany, HM Gurney, JG Khanna, G Jackson, HA Gordon, G Shusterman, S Park, JR Cohn, SL Adamson, PC London, WB Maris, JM Balis, FM AF Fox, Elizabeth Mosse', Yael P. Meany, Holly M. Gurney, James G. Khanna, Geetika Jackson, Hollie A. Gordon, Gary Shusterman, Suzanne Park, Julie R. Cohn, Susan L. Adamson, Peter C. London, Wendy B. Maris, John M. Balis, Frank M. TI Time to Disease Progression in Children With Relapsed or Refractory Neuroblastoma Treated With ABT-751: A Report from the Children's Oncology Group (ANBL0621) SO PEDIATRIC BLOOD & CANCER LA English DT Article DE childhood cancer; clinical trial; microtubule inhibitor; neuroblastoma; time to progression ID BIOAVAILABLE TUBULIN INHIBITOR; PEDIATRIC-PATIENTS; SOLID TUMORS; RELIABILITY; POPULATION; VALIDITY; CANCER AB BackgroundABT-751, an orally bioavailable sulfonamide binds the colchicine site of beta-tubulin and inhibits microtubule polymerizaton. Prior phase I studies established the recommended dose in children with solid tumors as 200mg/m(2) PO dailyx7 days every 21 days and subjects with neuroblastoma experienced prolonged stable disease. We conducted a phase 2 study (NCT00436852) in children and adolescents with progressive neuroblastoma to determine if ABT-751 prolonged the time to progression (TTP) compared to a hypothesized standard based on a historical control population. ProcedureChildren and adolescents (n=91) with a median (range) age 7.7 (2.3-21.5) years and progressive neuroblastoma were enrolled and stratified by disease status into disease measureable by CT/MRI (n=47) or disease assessable by I-123-metaiodobenzylguanine scintigraphy (MIBG, n=44). Response was evaluated using RECIST for measureable disease and the Curie score for MIBG-avid disease. ResultsABT-751 was well tolerated. The objective response rate was 7%. The median TTP was 42 days (95% CI: 36, 56) in the measureable disease stratum and 45 days (95% CI: 42, 85) in the MIBG-avid disease stratum. TTP was similar to the historical control group (n=136, median TTP 42 days). For the combined strata (n=91), 1-year progression free survival (PFS) was 134% and overall survival (OS) was 48 +/- 5%. ConclusionsThe low objective response rate and failure to prolong TTP indicate that ABT-751 is not sufficiently active to warrant further development for neuroblastoma. However, this trial demonstrates the utility of TTP as the primary endpoint in phase 2 trials in children and adolescents with neuroblastoma. Pediatr Blood Cancer 2014;61:990-996. (c) 2013 Wiley Periodicals, Inc. C1 [Fox, Elizabeth; Mosse', Yael P.; Adamson, Peter C.; Maris, John M.; Balis, Frank M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Meany, Holly M.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Gurney, James G.] Univ Memphis, Sch Publ Hlth, Memphis, TN 38152 USA. [Gurney, James G.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Khanna, Geetika] Washington Univ, Sch Med, St Louis, MO USA. [Jackson, Hollie A.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Gordon, Gary] Abbott Labs, Abbott Pk, IL 60064 USA. [Shusterman, Suzanne; London, Wendy B.] Boston Childrens Hosp, Boston, MA USA. [Shusterman, Suzanne; London, Wendy B.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Park, Julie R.] Seattle Childrens Hosp, Seattle, WA USA. [Cohn, Susan L.] Univ Chicago, Chicago, IL 60637 USA. [London, Wendy B.] Children Oncol Grp Stat & Data Ctr, Gainesville, FL USA. RP Fox, E (reprint author), Childrens Hosp Philadelphia, CTRB4016,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM foxe@email.chop.edu OI Cohn, Susan/0000-0001-5749-7650 FU Abbott Laboratories (Abbott Park, IL); National Cancer Institute of the NIH [U10 CA 098453, U10 CA98413] FX Grant sponsor: Abbott Laboratories (Abbott Park, IL); Grant sponsor: National Cancer Institute of the NIH; Grant numbers: U10 CA 098453; U10 CA98413 NR 15 TC 7 Z9 8 U1 1 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 JUN PY 2014 VL 61 IS 6 BP 990 EP 996 DI 10.1002/pbc.24900 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AE9IC UT WOS:000334320100010 PM 24347462 ER PT J AU Hitzler, JK He, WS Doyle, J Cairo, M Camitta, BM Chan, KW Perez, MAD Fraser, C Gross, TG Horan, JT Kennedy-Nasser, AA Kitko, C Kurtzberg, J Lehmann, L O'Brien, T Pulsipher, MA Smith, FO Zhang, MJ Eapen, M Carpenter, PA AF Hitzler, Johann K. He, Wensheng Doyle, John Cairo, Mitchell Camitta, Bruce M. Chan, Ka Wah Diaz Perez, Miguel A. Fraser, Christopher Gross, Thomas G. Horan, John T. Kennedy-Nasser, Alana A. Kitko, Carrie Kurtzberg, Joanne Lehmann, Leslie O'Brien, Tracey Pulsipher, Michael A. Smith, Franklin O. Zhang, Mei-Jie Eapen, Mary Carpenter, Paul A. CA CIBMTR Pediat Canc Working Comm TI Outcome of Transplantation for Acute Lymphoblastic Leukemia in Children With Down Syndrome SO PEDIATRIC BLOOD & CANCER LA English DT Article DE acute lymhoblastic leukemia; Down syndrome; hematopoietic stem cell transplantation; pediatric; relapse; trisomy 21 ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; 2ND REMISSION; TOXICITY; FAILURE; REGIMEN; RELAPSE AB We report on 27 patients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) who received allogeneic hematopoietic cell transplantation (HCT) between 2000 and 2009. Seventy-eight percent of patients received myeloablative conditioning and 52% underwent transplantation in second remission. Disease-free survival (DFS) was 24% at a median of 3 years. Post-transplant leukemic relapse was more frequent than expected for children with DS-ALL (54%) than for non-DS ALL. These data suggest leukemic relapse rather than transplant toxicity is the most important cause of treatment failure. Advancements in leukemia control are especially needed for improvement in HCT outcomes for DS-ALL. Pediatr Blood Cancer 2014;61:1126-1128. (c) 2014 Wiley Periodicals, Inc. C1 [Hitzler, Johann K.; Doyle, John] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [He, Wensheng; Zhang, Mei-Jie; Eapen, Mary] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Cairo, Mitchell] New York Med Coll, Valhalla, NY 10595 USA. [Camitta, Bruce M.] Med Coll Wisconsin, Midwest Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA. [Chan, Ka Wah] Texas Transplant Inst, San Antonio, TX USA. [Diaz Perez, Miguel A.] Hosp Nino Jesus, Madrid, Spain. [Fraser, Christopher] Royal Childrens Hosp, Herston, Qld, Australia. [Gross, Thomas G.] Nationwide Childrens Hosp, Columbus, OH USA. [Horan, John T.] Childrens Healthcare Atlanta Egleston, Atlanta, GA USA. [Kennedy-Nasser, Alana A.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Kitko, Carrie] Univ Michigan, Ann Arbor, MI 48109 USA. [Kurtzberg, Joanne] Duke Univ, Durham, NC USA. [Lehmann, Leslie] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Brien, Tracey] Sydney Childrens Hosp, Sydney, NSW, Australia. [Pulsipher, Michael A.] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Smith, Franklin O.] Univ Cincinnati, Inst Canc, Cincinnati, OH USA. [Carpenter, Paul A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Carpenter, PA (reprint author), Fred Hutchinson Canc Res Ctr, Mailstop D5-290,1024 Fairview Ave N, Seattle, WA 98109 USA. EM pcarpent@fhcrc.org FU Public Health Service [U24-CA76518]; National Cancer Institute; National Heart Lung and Blood Institute; National Institute of Allergy and Infectious Diseases and Heath Resources and Services Administration [HHSH234200637015C] FX Grant sponsor: Public Health Service; Grant number: U24-CA76518; Grant sponsor: National Cancer Institute; Grant sponsor: National Heart Lung and Blood Institute; Grant sponsor: National Institute of Allergy and Infectious Diseases and Heath Resources and Services Administration; Grant number: HHSH234200637015C NR 18 TC 3 Z9 3 U1 0 U2 1 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 JUN PY 2014 VL 61 IS 6 BP 1126 EP 1128 DI 10.1002/pbc.24918 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AE9IC UT WOS:000334320100036 PM 24391118 ER PT J AU Nowak, J Seidel, C Pietsch, T Friedrich, C von Hoff, K Rutkowski, S Warmuth-Metz, M AF Nowak, Johannes Seidel, Carolin Pietsch, Torsten Friedrich, Carsten von Hoff, Katja Rutkowski, Stefan Warmuth-Metz, Monika TI Ependymoblastoma of the Brainstem: MRI Findings and Differential Diagnosis SO PEDIATRIC BLOOD & CANCER LA English DT Article DE atypical teratoid; rhabdoid tumor; diffuse intrinsic pontine glioma; embryonal tumor with abundant neuropil and true rosettes; ependymoblastoma; medulloblastoma; primitive neuroectodermal tumor ID CENTRAL-NERVOUS-SYSTEM; TRUE ROSETTES ETANTR; OF-THE-LITERATURE; CASE-BASED UPDATE; ABUNDANT NEUROPIL; EMBRYONAL TUMOR AB Ependymoblastoma (EBL) is a rare malignant CNS tumor of early childhood, listed as a subgroup of primitive neuroectodermal tumors (PNET) in the 2007 WHO Classification of Tumours of the Central Nervous System. Histologically, EBL can be defined by multilayered, mitotically active ependymoblastic rosettes with central lumen as a histological hallmark. The prognosis seems to be far inferior to other embryonal CNS tumors, and known clinical and MRI characteristics of EBL are based on scattered case reports. We present and discuss two uncommon cases of histopathologically confirmed ependymoblastoma that both seem to originate from the brainstem. Pediatr Blood Cancer 2014;61:1132-1134. (c) 2014 Wiley Periodicals, Inc. C1 [Nowak, Johannes; Seidel, Carolin; Warmuth-Metz, Monika] Univ Hosp Wurzburg, Reference Ctr Neuroradiol, D-97080 Wurzburg, Germany. [Seidel, Carolin] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Pietsch, Torsten] Univ Bonn, Dept Neuropathol, Bonn, Germany. [Friedrich, Carsten; von Hoff, Katja; Rutkowski, Stefan] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Hematol & Oncol, Hamburg, Germany. RP Warmuth-Metz, M (reprint author), Univ Hosp Wurzburg, Reference Ctr Neuroradiol, Josef Schneider Str 11, D-97080 Wurzburg, Germany. EM warmuth_m@ukw.de FU Deutsche Kinderkrebsstiftung (German Childhood Cancer Foundation) FX Grant sponsor: Deutsche Kinderkrebsstiftung (German Childhood Cancer Foundation) NR 20 TC 3 Z9 4 U1 0 U2 8 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 JUN PY 2014 VL 61 IS 6 BP 1132 EP 1134 DI 10.1002/pbc.24915 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA AE9IC UT WOS:000334320100038 PM 24464920 ER PT J AU Goldberg, J Magruder, KM Forsberg, CW Kazis, LE Ustun, TB Friedman, MJ Litz, BT Vaccarino, V Heagerty, PJ Gleason, TC Huang, GD Smith, NL AF Goldberg, Jack Magruder, Kathryn M. Forsberg, Christopher W. Kazis, Lewis E. Uestuen, T. Bedirhan Friedman, Matthew J. Litz, Brett T. Vaccarino, Viola Heagerty, Patrick J. Gleason, Theresa C. Huang, Grant D. Smith, Nicholas L. TI The association of PTSD with physical and mental health functioning and disability (VA Cooperative Study #569: the course and consequences of posttraumatic stress disorder in Vietnam-era Veteran twins) SO QUALITY OF LIFE RESEARCH LA English DT Article DE PTSD; Vietnam-era Veterans; VR-36; WHODAS 2.0 ID QUALITY-OF-LIFE; COMBAT EXPOSURE; SYMPTOMS; REGISTRY; ORGANIZATION; COMORBIDITY; VERSION; SF-36; CIDI AB To assess the relationship of posttraumatic stress disorder (PTSD) with health functioning and disability in Vietnam-era Veterans. A cross-sectional study of functioning and disability in male Vietnam-era Veteran twins. PTSD was measured by the Composite International Diagnostic Interview; health functioning and disability were assessed using the Veterans RAND 36-Item Health Survey (VR-36) and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). All data collection took place between 2010 and 2012. Average age of the 5,574 participating Veterans (2,102 Vietnam theater and 3,472 non-theater) was 61.0 years. Veterans with PTSD had poorer health functioning across all domains of VR-36 and increased disability for all subscales of WHODAS 2.0 (all p < .001) compared with Veterans without PTSD. Veterans with PTSD were in poorer overall health on the VR-36 physical composite summary (PCS) (effect size = 0.31 in theater and 0.47 in non-theater Veterans; p < .001 for both) and mental composite summary (MCS) (effect size = 0.99 in theater and 0.78 in non-theater Veterans; p < .001 for both) and had increased disability on the WHODAS 2.0 summary score (effect size = 1.02 in theater and 0.96 in non-theater Veterans; p < .001 for both). Combat exposure, independent of PTSD status, was associated with lower PCS and MCS scores and increased disability (all p < .05, for trend). Within-pair analyses in twins discordant for PTSD produced consistent findings. Vietnam-era Veterans with PTSD have diminished functioning and increased disability. The poor functional status of aging combat-exposed Veterans is of particular concern. C1 [Goldberg, Jack; Forsberg, Christopher W.; Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr S152E, Seattle, WA 98108 USA. [Goldberg, Jack; Smith, Nicholas L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Magruder, Kathryn M.] Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. [Magruder, Kathryn M.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Kazis, Lewis E.] Bedford VAMC, Ctr Hlth Qual Outcomes & Econ Res CHQOER, Bedford, MA USA. [Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Uestuen, T. Bedirhan] WHO, Classificat & Terminol Team, CH-1211 Geneva, Switzerland. [Friedman, Matthew J.] Natl Ctr Posttraumat Stress Disorder, Dept Vet Affairs, White River Jct, VT USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Pharmacol & Psychiat, Hanover, NH USA. [Friedman, Matthew J.] Geisel Sch Med Dartmouth, Dept Toxicol, Hanover, NH USA. [Litz, Brett T.] VA Boston Healthcare Syst, Massachusetts Epidemiol Res & Informat Ctr, Boston, MA USA. [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Vaccarino, Viola] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. [Heagerty, Patrick J.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Gleason, Theresa C.; Huang, Grant D.] VA Off Res & Dev, Cooperat Studies Program, Washington, DC USA. RP Goldberg, J (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr S152E, 1600 South Columbian Way, Seattle, WA 98108 USA. EM jack.goldberg@va.gov FU Cooperative Studies Program (CSP) of the Office of Research and Development, Clinical Science Research and Development of the United States Department of Veterans Affairs (VA) [569]; National Institutes of Health [K24 HL077506] FX Dr. Goldberg 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. The funding source was involved in the design and conduct of the study, and the interpretation, preparation, review, and approval of the manuscript. The authors were responsible for the collection, management, analysis, and interpretation of the data and for the preparation of the manuscript and its submission for publication. The authors gratefully acknowledge the continued cooperation and participation of the members of the VET Registry: without their contribution this research would not have been possible. The authors would also like to thank the members of the Department of Veterans Affairs Cooperative Study #569 Group (in addition to the authors): I. Curtis, A. Ali, B. Majerczyk, B. Harp, K. Moore, A. Fox, M. Tsai, A. Mori, J. Sporleder, P. Terry, Seattle, WA; D. Yeager, Charleston, SC. Executive Committee: S. Eisen, Washington, DC; A. Snodgrass, Albuquerque, NM. Data Monitoring Committee: J. Vasterling, Boston, MA; M. Stein, La Jolla, CA; B. Booth, Little Rock, AR; J. Westermeyer, Minneapolis, MN. Planning Committee: M. McFall, Seattle, WA; T. O'Leary, S. Eisen, Washington, DC; M. Smith, Palo Alto, CA; K. Swanson, Albuquerque, NM. SF-36 (R) is a registered trademark of the Medical Outcomes Trust. The Cooperative Studies Program (CSP) of the Office of Research and Development, Clinical Science Research and Development, of the United States Department of Veterans Affairs (VA), has provided financial support for Cooperative Study #569 and the development and maintenance of the Vietnam Era Twin (VET) Registry. Dr. Viola Vaccarino was supported in part by a National Institutes of Health award, K24 HL077506 NR 41 TC 12 Z9 12 U1 0 U2 6 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 JUN PY 2014 VL 23 IS 5 BP 1579 EP 1591 DI 10.1007/s11136-013-0585-4 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AH8YD UT WOS:000336423200017 PM 24318083 ER PT J AU Conhaim, RL Watson, KE Dovi, WF Bates, ML AF Conhaim, Robert L. Watson, Kal E. Dovi, William F. Bates, Melissa L. TI INHALED THROMBOLYTICS REDUCE LUNG MICROCLOT AND LEUKOCYTE INFILTRATION AFTER ACUTE BLOOD LOSS SO SHOCK LA English DT Article DE Acute lung injury; neutrophils; thromboembolism; shock lung; pulmonary circulation; fibrinolysis ID NEBULIZED ANTICOAGULANTS; INTERALVEOLAR PERFUSION; FIBRIN; RATS; INJURY; MICROVESSELS; COAGULOPATHY; INFLAMMATION; EDEMA AB We showed previously that a 30% blood loss in rats, without resuscitation, caused significant accumulation of microthrombi and leukocytes within the pulmonary circulation by 24 h. We hypothesized that the microthrombi formed spontaneously as a consequence of hemorrhage-induced stasis within the low-pressure pulmonary circuit and that the leukocytes were attracted to them. This suggested that elimination of the microthrombi, using an inhaled thrombolytic agent, could prevent the neutrophil sequestration after blood loss. To test this hypothesis, we removed 30% of the calculated blood volume from isoflurane-anesthetized, male Sprague-Dawley rats (350-500 g) over 5 min and allowed them to recover. Six hours later, we reanesthetized the rats and nebulized tissue plasminogen activator (80 or 320 mu g/kg), lactated Ringer's solution (LRS), or ipratropium bromide (i-bromide) into their lungs. We used i-bromide as a control after we discovered that nebulized LRS had thrombolytic properties. At 24 h, we removed and fixed the lungs and prepared sections for immunohistochemistry using antibodies against fibrinogen (microthrombi) and CD16 (leukocytes). Digital images of each section were obtained using a confocal microscope. Pixel counts of the images showed significantly less accumulation of microthrombi and leukocytes in lungs nebulized with tissue plasminogen activator or LRS than in nonnebulized lungs or in lungs nebulized with i-bromide (P 0.05). Lactated Ringer's solution becomes positively charged when nebulized (unlike i-bromide), suggesting that it eliminated microthrombi by fibrin depolymerization. We confirmed this using an in vitro assay. Our results demonstrate that lyses of microthrombi that accumulate in the lung after acute blood loss prevent subsequent leukocyte sequestration. C1 [Conhaim, Robert L.; Watson, Kal E.] Univ Wisconsin, Dept Surg, Sch Med & Publ Heath, Madison, WI USA. [Conhaim, Robert L.; Dovi, William F.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Bates, Melissa L.] Univ Wisconsin, Dept Pediat, Sch Med & Publ Heath, Madison, WI USA. RP Conhaim, RL (reprint author), H5-301-BX3236,600 Highland Ave, Madison, WI 53792 USA. EM rconhaim@wisc.edu FU Veterans Health Administration, Office of Research and Development, Department of Veterans Affairs, Biomedical Laboratory Research and Development Service FX This study was supported by the Veterans Health Administration, Office of Research and Development, Department of Veterans Affairs, Biomedical Laboratory Research and Development Service (R. L. C., principal investigator). NR 24 TC 1 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 EI 1540-0514 J9 SHOCK JI Shock PD JUN PY 2014 VL 41 IS 6 BP 528 EP 536 DI 10.1097/SHK.0000000000000149 PG 9 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA AH6CI UT WOS:000336217900010 PM 24837203 ER PT J AU Dunn, EC Masyn, KE Yudron, M Jones, SM Subramanian, SV AF Dunn, Erin C. Masyn, Katherine E. Yudron, Monica Jones, Stephanie M. Subramanian, S. V. TI Translating multilevel theory into multilevel research: challenges and opportunities for understanding the social determinants of psychiatric disorders SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Multilevel; Social determinants; Social and physical environments; Ecological; Context; Composition; Psychiatric disorders ID MENTAL-HEALTH; NEIGHBORHOOD CHARACTERISTICS; BIOLOGICAL SENSITIVITY; SYSTEMS SCIENCE; FUTURE-RESEARCH; MODELS; DEPRESSION; ENVIRONMENT; VIEW; EPIDEMIOLOGY AB The observation that features of the social environment, including family, school, and neighborhood characteristics, are associated with individual-level outcomes has spurred the development of dozens of multilevel or ecological theoretical frameworks in epidemiology, public health, psychology, and sociology, among other disciplines. Despite the widespread use of such theories in etiological, intervention, and policy studies, challenges remain in bridging multilevel theory and empirical research. This paper set out to synthesize these challenges and provide specific examples of methodological and analytical strategies researchers are using to gain a more nuanced understanding of the social determinants of psychiatric disorders, with a focus on children's mental health. To accomplish this goal, we begin by describing multilevel theories, defining their core elements, and discussing what these theories suggest is needed in empirical work. In the second part, we outline the main challenges researchers face in translating multilevel theory into research. These challenges are presented for each stage of the research process. In the third section, we describe two methods being used as alternatives to traditional multilevel modeling techniques to better bridge multilevel theory and multilevel research. These are (1) multilevel factor analysis and multilevel structural equation modeling; and (2) dynamic systems approaches. Through its review of multilevel theory, assessment of existing strategies, and examination of emerging methodologies, this paper offers a framework to evaluate and guide empirical studies on the social determinants of child psychiatric disorders as well as health across the life course. C1 [Dunn, Erin C.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02144 USA. [Masyn, Katherine E.; Yudron, Monica; Jones, Stephanie M.] Harvard Univ, Harvard Grad Sch Educ, Cambridge, MA 02138 USA. [Subramanian, S. V.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, 185 Cambridge St, Boston, MA 02144 USA. EM erindunn@pngu.mgh.harvard.edu FU NIMH NIH HHS [F31 MH088074, K01 MH102403] NR 86 TC 8 Z9 8 U1 3 U2 28 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 EI 1433-9285 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD JUN PY 2014 VL 49 IS 6 BP 859 EP 872 DI 10.1007/s00127-013-0809-5 PG 14 WC Psychiatry SC Psychiatry GA AH7BR UT WOS:000336287900003 PM 24469555 ER PT J AU Manchikanti, L Falco, FJE Hirsch, JA AF Manchikanti, Laxmaiah Falco, Frank J. E. Hirsch, Joshua A. TI Evidence-based guidelines improperly assessed epidural injections SO SPINE JOURNAL LA English DT Letter ID LUMBAR DISC HERNIATION; DOUBLE-BLIND TRIAL; RANDOMIZED CONTROLLED-TRIAL; RADICULAR PAIN; PERIRADICULAR INFILTRATION; STEROID INJECTIONS; SUBGROUP ANALYSIS; FOLLOW-UP; SCIATICA; INTERLAMINAR C1 [Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Paducah, KY 42003 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys, Newark, DE 19713 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), Univ Louisville, Dept Anesthesiol & Perioperat Med, 2831 Lone Oak Rd, Paducah, KY 42003 USA. NR 20 TC 0 Z9 0 U1 0 U2 4 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 JUN PY 2014 VL 14 IS 6 BP 1086 EP 1087 DI 10.1016/j.spinee.2014.01.029 PG 3 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA AH8UA UT WOS:000336412500047 PM 24851737 ER PT J AU Barrisford, GW Gershman, B Blute, ML AF Barrisford, Glen W. Gershman, Boris Blute, Michael L., Sr. TI The role of lymphadenectomy in the management of renal cell carcinoma SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Renal cell carcinoma; Renal cancer; Lymphadenectomy; Lymph node dissection ID LYMPH-NODE DISSECTION; PROSPECTIVE CLINICAL-TRIALS; RADICAL NEPHRECTOMY; STRATIFICATION TOOL; SURGICAL RESECTION; SURVIVAL; CANCER; PROGRESSION; METASTASES; PREDICTION AB The role of lymphadenectomy in the management of renal cell carcinoma has been established in staging but is less well defined as a therapeutic maneuver. Level one evidence suggests no survival benefit or increased complication rate with lymphadenectomy when performed concurrently with radical nephrectomy. However, several retrospective studies have identified a survival benefit when patients with increased risk of micrometastatic lymph node disease undergo lymphadenectomy. We perform a selective review of the literature and present the historical basis, risk assessment, use and development of nodal templates, and therapeutic benefits associated with the use of lymphadenectomy in the management of renal cell carcinoma. C1 [Barrisford, Glen W.; Gershman, Boris; Blute, Michael L., Sr.] Harvard Univ, Massachusetts Gen Hosp, Dept Urol, Sch Med, Boston, MA 02114 USA. RP Blute, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Urol, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM gbarrisford@partners.org; mblute@partners.org NR 28 TC 1 Z9 1 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD JUN PY 2014 VL 32 IS 3 BP 643 EP 649 DI 10.1007/s00345-014-1294-5 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AH8RL UT WOS:000336405800010 PM 24723269 ER PT J AU Sammon, JD Sharma, P Rahbar, H Roghmann, F Ghani, KR Sukumar, S Karakiewicz, PI Peabody, JO Elder, JS Menon, M Sun, M Trinh, QD AF Sammon, Jesse D. Sharma, Pranav Rahbar, Haider Roghmann, Florian Ghani, Khurshid R. Sukumar, Shyam Karakiewicz, Pierre I. Peabody, James O. Elder, Jack S. Menon, Mani Sun, Maxine Quoc-Dien Trinh TI Predictors of admission in patients presenting to the emergency department with urinary tract infection SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Urinary tract infection; Emergency department; Predictors of admission; Nationwide Emergency Department Sample (NEDS) ID ACUTE PYELONEPHRITIS; UROLOGIC DISEASES; AMERICA PROJECT; RESOURCE USE; WOMEN; HOSPITALIZATION; BEHAVIOR; THERAPY; ADULTS; TRENDS AB Previous studies examining the management of urinary tract infections (UTI) showed marked variability in the economical burden of care, with a tenfold increase in costs when patients require admission to the hospital. We sought to examine the patient and emergency department (ED) characteristics associated with hospitalization in patients presenting to the ED with UTI. An estimate of 10,798,343 patients with a primary diagnosis of UTI was presented to the ED from 2006 to 2009 and was abstracted from the Nationwide Emergency Department Sample. Univariable and multivariable analyses examined patient and hospital characteristics of those admitted with UTI. Between 2006 and 2009, 10.8 million patients presented to the ED in the United States for the treatment of UTI and 1.8 million patients (16.7 %) were admitted to the hospital for further management. Admitted patients were older, and a higher proportion had pyelonephritis, was male, and had Medicare. Admitted patients were also more likely to be seen at urban teaching hospitals, and/or treated at zip codes with higher median incomes. Following multivariable analysis, the independent predictors of admission included pyelonephritis (OR 5.29, 95 % CI 5.23-5.35), male gender (OR 1.58, 95 % CI 1.56-1.59), and advancing age (OR 1.037, 95 % CI 1.037-1.037). Expansion in ED utilization for the management of UTI has exceeded previous estimates. While the preponderance of patients presenting to the ED for UTI is discharged home, 16.7 % are admitted for further management. Predictors of inpatient admission on multivariable analyses included pyelonephritis, advancing age, and male gender. C1 [Sammon, Jesse D.; Sharma, Pranav; Ghani, Khurshid R.; Sukumar, Shyam; Peabody, James O.; Elder, Jack S.; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI 48202 USA. [Sammon, Jesse D.; Sharma, Pranav; Ghani, Khurshid R.; Sukumar, Shyam] Henry Ford Hlth Syst, VUI Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA. [Rahbar, Haider] Wayne State Univ, Sch Med, Detroit, MI USA. [Roghmann, Florian; Karakiewicz, Pierre I.; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol,Dept Surg,Med Sch, Boston, MA 02115 USA. RP Sammon, JD (reprint author), Henry Ford Hlth Syst, Vattikuti Urol Inst, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM jsammon79@gmail.com NR 25 TC 2 Z9 3 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD JUN PY 2014 VL 32 IS 3 BP 813 EP 819 DI 10.1007/s00345-013-1167-3 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AH8RL UT WOS:000336405800031 PM 24072010 ER PT J AU Paruch, JL Merkow, RP Bentrem, DJ Ko, CY Posner, MC Cohen, ME Bilimoria, KY Weber, SM AF Paruch, Jennifer L. Merkow, Ryan P. Bentrem, David J. Ko, Clifford Y. Posner, Mitchell C. Cohen, Mark E. Bilimoria, Karl Y. Weber, Sharon M. TI Impact of Hepatectomy Surgical Complexity on Outcomes and Hospital Quality Rankings SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID RISK-ADJUSTMENT; IMPROVEMENT PROGRAM; LIVER RESECTION; NSQIP; SURGERY; MODELS AB There is substantial variation in the surgical complexity of hepatectomy. Currently, the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) risk adjusts for hospital quality comparisons using only the primary procedure code. Our objectives were to (1) assess the association between secondary procedures and complications; (2) assess model performance with inclusion of surgical complexity adjustment; and (3) examine whether secondary procedures affect hospital quality rankings. Using ACS NSQIP (2007-2012), patients undergoing hepatectomy were identified. Secondary procedure codes and total work relative value units (RVUs) were used to approximate procedural complexity. The effect of procedural complexity variables on outcomes and hospital quality rankings were examined using hierarchical models. Among 11,826 patients who underwent hepatectomy at 261 hospitals, 32.8 % underwent at least one secondary procedure. Serious morbidity occurred in 18.0 % of patients. Seven of nine secondary procedures were significantly associated with death or serious morbidity on multivariable analysis. Model performance improved when secondary procedure categories were included, and secondary procedure categories outperformed total RVUs. The C-statistic for death or serious morbidity was 0.689 in the standard NSQIP model, 0.703 when total RVU was included, and 0.718 when secondary procedure categories were included. Of the 26 hospitals that were poor performers for death or serious morbidity using the standard ACS NSQIP model, three became average performers when secondary procedure categories were included in the model. Secondary procedures are associated with an increased risk of postoperative complications. Inclusion of secondary procedure code categories in research and risk prediction models should be considered for hepatectomy. C1 [Paruch, Jennifer L.; Merkow, Ryan P.; Ko, Clifford Y.; Cohen, Mark E.; Bilimoria, Karl Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. [Paruch, Jennifer L.; Merkow, Ryan P.; Posner, Mitchell C.] Univ Chicago, Dept Surg, Pritzker Sch Med, Chicago, IL 60637 USA. [Merkow, Ryan P.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Dept Surg, Surg Outcomes & Qual Improvement Ctr, Feinberg Sch Med, Chicago, IL 60611 USA. [Merkow, Ryan P.; Bentrem, David J.; Bilimoria, Karl Y.] Northwestern Univ, Northwestern Inst Comparat Effectiveness Res Onco, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Dept Surg, Chicago, IL USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Weber, Sharon M.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. RP Paruch, JL (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, Chicago, IL 60611 USA. EM jlparuch@gmail.com FU American Cancer Society; National Comprehensive Cancer Network FX This work was supported in part by the American Cancer Society (Drs. Merkow and Bilimoria) and the National Comprehensive Cancer Network (Dr. Bilimoria). NR 20 TC 8 Z9 8 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2014 VL 21 IS 6 BP 1773 EP 1780 DI 10.1245/s10434-014-3500-5 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA AG9GH UT WOS:000335726900005 PM 24558060 ER PT J AU Thompson, PM Stein, JL Medland, SE Hibar, DP Vasquez, AA Renteria, ME Toro, R Jahanshad, N Schumann, G Franke, B Wright, MJ Martin, NG Agartz, I Alda, M Alhusaini, S Almasy, L Almeida, J Alpert, K Andreasen, NC Andreassen, OA Apostolova, LG Appel, K Armstrong, NJ Aribisala, B Bastin, ME Bauer, M Bearden, CE Bergmann, O Binder, EB Blangero, J Bockholt, HJ Boen, E Bois, C Boomsma, DI Booth, T Bowman, IJ Bralten, J Brouwer, RM Brunner, HG Brohawn, DG Buckner, RL Buitelaar, J Bulayeva, K Bustillo, JR Calhoun, VD Cannon, DM Cantor, RM Carless, MA Caseras, X Cavalleri, GL Chakravarty, MM Chang, KD Ching, CRK Christoforou, A Cichon, S Clark, VP Conrod, P Coppola, G Crespo-Facorro, B Curran, JE Czisch, M Deary, IJ de Geus, EJC den Braber, A Delvecchio, G Depondt, C de Haan, L de Zubicaray, GI Dima, D Dimitrova, R Djurovic, S Dong, HW Donohoe, G Duggirala, R Dyer, TD Ehrlich, S Ekman, CJ Elvsashagen, T Emsell, L Erk, S Espeseth, T Fagerness, J Fears, S Fedko, I Fernandez, G Fisher, SE Foroud, T Fox, PT Francks, C Frangou, S Frey, EM Frodl, T Frouin, V Garavan, H Giddaluru, S Glahn, DC Godlewska, B Goldstein, RZ Gollub, RL Grabe, HJ Grimm, O Gruber, O Guadalupe, T Gur, RE Gur, RC Goring, H Hagenaars, S Hajek, T Hall, GB Hall, J Hardy, J Hartman, CA Hass, J Hatton, SN Haukvik, UK Hegenscheid, K Heinz, A Hickie, IB Ho, BC Hoehn, D Hoekstra, PJ Hollinshead, M Holmes, AJ Homuth, G Hoogman, M Hong, LE Hosten, N Hottenga, JJ Pol, HEH Hwang, KS Jack, CR Jenkinson, M Johnston, C Jonsson, E Kahn, R Kasperaviciute, D Kelly, S Kim, S Kochunov, P Koenders, L Kramer, B Kwok, JBJ Lagopoulos, J Laje, G Landen, M Landman, BA Lauriello, J Lawrie, SM Lee, PH Le Hellard, S Lemaitre, H Leonardo, CD Li, CS Liberg, B Liewald, DC Liu, XM Lopez, LM Loth, E Lourdusamy, A Luciano, M Macciardi, F Machielsen, MWJ MacQueen, GM Malt, UF Mandl, R Manoach, DS Martinot, JL Matarin, M Mather, KA Mattheisen, M Mattingsdal, M Meyer-Lindenberg, A McDonald, C McIntosh, AM McMahon, FJ McMahon, KL Meisenzahl, E Melle, I Milaneschi, Y Mohnke, S Montgomery, GW Morris, DW Moses, EK Mueller, BA Munoz Maniega, S Muhleisen, T Muller-Myhsok, B Mwangi, B Nauck, M Nho, K Nichols, TE Nilsson, LG Nugent, AC Nyberg, L Olvera, RL Oosterlaan, J Ophoff, RA Pandolfo, M Papalampropoulou-Tsiridou, M Papmeyer, M Paus, T Pausova, Z Pearlson, GD Penninx, BW Peterson, CP Pfennig, A Phillips, M Pike, GB Poline, JB Potkin, SG Putz, B Ramasamy, A Rasmussen, J Rietschel, M Rijpkema, M Risacher, SL Roffman, JL Roiz-Santianez, R Romanczuk-Seiferth, N Rose, EJ Royle, NA Rujescu, D Ryten, M Sachdev, PS Salami, A Satterthwaite, TD Savitz, J Saykin, AJ Scanlon, C Schmaal, L Schnack, HG Schork, AJ Schulz, SC Schur, R Seidman, L Shen, L Shoemaker, JM Simmons, A Sisodiya, SM Smith, C Smoller, JW Soares, JC Sponheim, SR Sprooten, E Starr, JM Steen, VM Strakowski, S Strike, L Sussmann, J Samann, PG Teumer, A Toga, AW Tordesillas-Gutierrez, D Trabzuni, D Trost, S Turner, J Van den Heuvel, M Van der Wee, NJ van Eijk, K van Erp, TGM van Haren, NEM Van 't Ent, D van Tol, MJ Hernandez, MCV Veltman, DJ Versace, A Volzke, H Walker, R Walter, H Wang, L Wardlaw, JM Weale, ME Weiner, MW Wen, W Westlye, LT Whalley, HC Whelan, CD White, T Winkler, AM Wittfeld, K Woldehawariat, G Wolf, C Zilles, D Zwiers, MP Thalamuthu, A Schofield, PR Freimer, NB Lawrence, NS Drevets, W AF Thompson, Paul M. Stein, Jason L. Medland, Sarah E. Hibar, Derrek P. Vasquez, Alejandro Arias Renteria, Miguel E. Toro, Roberto Jahanshad, Neda Schumann, Gunter Franke, Barbara Wright, Margaret J. Martin, Nicholas G. Agartz, Ingrid Alda, Martin Alhusaini, Saud Almasy, Laura Almeida, Jorge Alpert, Kathryn Andreasen, Nancy C. Andreassen, Ole A. Apostolova, Liana G. Appel, Katja Armstrong, Nicola J. Aribisala, Benjamin Bastin, Mark E. Bauer, Michael Bearden, Carrie E. Bergmann, Orjan Binder, Elisabeth B. Blangero, John Bockholt, Henry J. Boen, Erlend Bois, Catherine Boomsma, Dorret I. Booth, Tom Bowman, Ian J. Bralten, Janita Brouwer, Rachel M. Brunner, Han G. Brohawn, David G. Buckner, Randy L. Buitelaar, Jan Bulayeva, Kazima Bustillo, Juan R. Calhoun, Vince D. Cannon, Dara M. Cantor, Rita M. Carless, Melanie A. Caseras, Xavier Cavalleri, Gianpiero L. Chakravarty, M. Mallar Chang, Kiki D. Ching, Christopher R. K. Christoforou, Andrea Cichon, Sven Clark, Vincent P. Conrod, Patricia Coppola, Giovanni Crespo-Facorro, Benedicto Curran, Joanne E. Czisch, Michael Deary, Ian J. de Geus, Eco J. C. den Braber, Anouk Delvecchio, Giuseppe Depondt, Chantal de Haan, Lieuwe de Zubicaray, Greig I. Dima, Danai Dimitrova, Rali Djurovic, Srdjan Dong, Hongwei Donohoe, Gary Duggirala, Ravindranath Dyer, Thomas D. Ehrlich, Stefan Ekman, Carl Johan Elvsashagen, Torbjorn Emsell, Louise Erk, Susanne Espeseth, Thomas Fagerness, Jesen Fears, Scott Fedko, Iryna Fernandez, Guillen Fisher, Simon E. Foroud, Tatiana Fox, Peter T. Francks, Clyde Frangou, Sophia Frey, Eva Maria Frodl, Thomas Frouin, Vincent Garavan, Hugh Giddaluru, Sudheer Glahn, David C. Godlewska, Beata Goldstein, Rita Z. Gollub, Randy L. Grabe, Hans J. Grimm, Oliver Gruber, Oliver Guadalupe, Tulio Gur, Raquel E. Gur, Ruben C. Goering, Harald H. H. Hagenaars, Saskia Hajek, Tomas Hall, Geoffrey B. Hall, Jeremy Hardy, John Hartman, Catharina A. Hass, Johanna Hatton, Sean N. Haukvik, Unn K. Hegenscheid, Katrin Heinz, Andreas Hickie, Ian B. Ho, Beng-Choon Hoehn, David Hoekstra, Pieter J. Hollinshead, Marisa Holmes, Avram J. Homuth, Georg Hoogman, Martine Hong, L. Elliot Hosten, Norbert Hottenga, Jouke-Jan Pol, Hilleke E. Hulshoff Hwang, Kristy S. Jack, Clifford R., Jr. Jenkinson, Mark Johnston, Caroline Joensson, Erik G. Kahn, Rene S. Kasperaviciute, Dalia Kelly, Sinead Kim, Sungeun Kochunov, Peter Koenders, Laura Kraemer, Bernd Kwok, John B. J. Lagopoulos, Jim Laje, Gonzalo Landen, Mikael Landman, Bennett A. Lauriello, John Lawrie, Stephen M. Lee, Phil H. Le Hellard, Stephanie Lemaitre, Herve Leonardo, Cassandra D. Li, Chiang-shan Liberg, Benny Liewald, David C. Liu, Xinmin Lopez, Lorna M. Loth, Eva Lourdusamy, Anbarasu Luciano, Michelle Macciardi, Fabio Machielsen, Marise W. J. MacQueen, Glenda M. Malt, Ulrik F. Mandl, Rene Manoach, Dara S. Martinot, Jean-Luc Matarin, Mar Mather, Karen A. Mattheisen, Manuel Mattingsdal, Morten Meyer-Lindenberg, Andreas McDonald, Colm McIntosh, Andrew M. McMahon, Francis J. McMahon, Katie L. Meisenzahl, Eva Melle, Ingrid Milaneschi, Yuri Mohnke, Sebastian Montgomery, Grant W. Morris, Derek W. Moses, Eric K. Mueller, Bryon A. Munoz Maniega, Susana Muehleisen, Thomas W. Mueller-Myhsok, Bertram Mwangi, Benson Nauck, Matthias Nho, Kwangsik Nichols, Thomas E. Nilsson, Lars-Goeran Nugent, Allison C. Nyberg, Lars Olvera, Rene L. Oosterlaan, Jaap Ophoff, Roel A. Pandolfo, Massimo Papalampropoulou-Tsiridou, Melina Papmeyer, Martina Paus, Tomas Pausova, Zdenka Pearlson, Godfrey D. Penninx, Brenda W. Peterson, Charles P. Pfennig, Andrea Phillips, Mary Pike, G. Bruce Poline, Jean-Baptiste Potkin, Steven G. Puetz, Benno Ramasamy, Adaikalavan Rasmussen, Jerod Rietschel, Marcella Rijpkema, Mark Risacher, Shannon L. Roffman, Joshua L. Roiz-Santianez, Roberto Romanczuk-Seiferth, Nina Rose, Emma J. Royle, Natalie A. Rujescu, Dan Ryten, Mina Sachdev, Perminder S. Salami, Alireza Satterthwaite, Theodore D. Savitz, Jonathan Saykin, Andrew J. Scanlon, Cathy Schmaal, Lianne Schnack, Hugo G. Schork, Andrew J. Schulz, S. Charles Schuer, Remmelt Seidman, Larry Shen, Li Shoemaker, Jody M. Simmons, Andrew Sisodiya, Sanjay M. Smith, Colin Smoller, Jordan W. Soares, Jair C. Sponheim, Scott R. Sprooten, Emma Starr, John M. Steen, Vidar M. Strakowski, Stephen Strike, Lachlan Sussmann, Jessika Saemann, Philipp G. Teumer, Alexander Toga, Arthur W. Tordesillas-Gutierrez, Diana Trabzuni, Daniah Trost, Sarah Turner, Jessica Van den Heuvel, Martijn van der Wee, Nic J. van Eijk, Kristel van Erp, Theo G. M. van Haren, Neeltje E. M. van 't Ent, Dennis van Tol, Marie-Jose Hernandez, Maria C. Valdes Veltman, Dick J. Versace, Amelia Voelzke, Henry Walker, Robert Walter, Henrik Wang, Lei Wardlaw, Joanna M. Weale, Michael E. Weiner, Michael W. Wen, Wei Westlye, Lars T. Whalley, Heather C. Whelan, Christopher D. White, Tonya Winkler, Anderson M. Wittfeld, Katharina Woldehawariat, Girma Wolf, Christiane Zilles, David Zwiers, Marcel P. Thalamuthu, Anbupalam Schofield, Peter R. Freimer, Nelson B. Lawrence, Natalia S. Drevets, Wayne CA Alzheimer's Dis Neuroimaging EPIGEN Consortium IMAGEN Consortium Saguenay Youth Study SYS Grp TI The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data SO BRAIN IMAGING AND BEHAVIOR LA English DT Article DE Genetics; MRI; GWAS; Consortium; Meta-analysis; Multi-site ID GENOME-WIDE ASSOCIATION; CORTICAL SURFACE-AREA; WHITE-MATTER MICROSTRUCTURE; MULTIVARIATE PARALLEL ICA; TENSOR-BASED MORPHOMETRY; QUANTITATIVE TRAIT LOCI; VOXEL-BASED MORPHOMETRY; HUMAN BRAIN STRUCTURE; DISEASE RISK VARIANT; BODY-MASS INDEX AB The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. C1 [Thompson, Paul M.; Hibar, Derrek P.; Jahanshad, Neda; Bowman, Ian J.; Ching, Christopher R. K.; Dong, Hongwei; Leonardo, Cassandra D.; Toga, Arthur W.] Univ So Calif, Imaging Genet Ctr, Inst Neuroimaging & Informat, Keck Sch Med, Los Angeles, CA 90033 USA. [Montgomery, Grant W.; Strike, Lachlan] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia. [Lee, Phil H.; Smoller, Jordan W.] Broad Inst Harvard & MIT, Boston, MA USA. [Vasquez, Alejandro Arias; Franke, Barbara; Bralten, Janita; Brunner, Han G.; Hoogman, Martine] Radboud Univ Nijmegen Med Ctr, Dept Human Genet, Nijmegen, Netherlands. [Vasquez, Alejandro Arias; Franke, Barbara; Bralten, Janita; Buitelaar, Jan; Fisher, Simon E.; Francks, Clyde; Rijpkema, Mark; Zwiers, Marcel P.] Radboud Univ Nijmegen Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Nijmegen, Netherlands. [Toro, Roberto] Inst Pasteur, Human Genet & Cognit Funct, Paris, France. [Toro, Roberto] Inst Pasteur, CNRS URA Genes Synapses & Cognit 2182, Paris, France. [Toro, Roberto] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Glahn, David C.] Hartford Hosp, Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT 06115 USA. [Glahn, David C.; Li, Chiang-shan; Pearlson, Godfrey D.; Winkler, Anderson M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Appel, Katja; Grabe, Hans J.] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany. [Andreassen, Ole A.; Christoforou, Andrea; Djurovic, Srdjan; Espeseth, Thomas; Giddaluru, Sudheer; Haukvik, Unn K.; Le Hellard, Stephanie; Mattingsdal, Morten; Melle, Ingrid; Steen, Vidar M.; Westlye, Lars T.] Univ Oslo, NORMENT, KG Jebsen Ctr Psychosis Res, Oslo Univ Hosp, Oslo, Norway. [Andreassen, Ole A.; Christoforou, Andrea; Djurovic, Srdjan; Espeseth, Thomas; Giddaluru, Sudheer; Haukvik, Unn K.; Le Hellard, Stephanie; Mattingsdal, Morten; Melle, Ingrid; Steen, Vidar M.; Westlye, Lars T.] Univ Oslo, Inst Clin Med, Oslo, Norway. [Alhusaini, Saud; Cavalleri, Gianpiero L.; Whelan, Christopher D.] Royal Coll Surgeons Ireland, Dept Mol & Cellular Therapeut, Dublin 2, Ireland. [Almasy, Laura; Blangero, John; Carless, Melanie A.; Curran, Joanne E.; Duggirala, Ravindranath; Dyer, Thomas D.; Goering, Harald H. H.; Moses, Eric K.; Peterson, Charles P.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA. [Andreasen, Nancy C.; Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [Apostolova, Liana G.; Coppola, Giovanni] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Aribisala, Benjamin; Bastin, Mark E.; Booth, Tom; Deary, Ian J.; Liewald, David C.; Lopez, Lorna M.; Luciano, Michelle; Munoz Maniega, Susana; Royle, Natalie A.; Starr, John M.; Hernandez, Maria C. Valdes; Wardlaw, Joanna M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Aribisala, Benjamin; Munoz Maniega, Susana; Wardlaw, Joanna M.] Scottish Imaging Network, St Andrews, Fife, Scotland. [Aribisala, Benjamin; Bastin, Mark E.; Munoz Maniega, Susana; Royle, Natalie A.; Hernandez, Maria C. Valdes; Wardlaw, Joanna M.] Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland. [Binder, Elisabeth B.; Czisch, Michael; Hoehn, David; Mueller-Myhsok, Bertram; Puetz, Benno; Saemann, Philipp G.; Wolf, Christiane] Max Planck Inst Psychiat, D-80804 Munich, Germany. [Calhoun, Vince D.; Shoemaker, Jody M.; Turner, Jessica] Mind Res Network, Albuquerque, NM USA. [Boomsma, Dorret I.; de Geus, Eco J. C.; den Braber, Anouk; Fedko, Iryna; Hottenga, Jouke-Jan; van 't Ent, Dennis] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Bralten, Janita; Fernandez, Guillen] Radboud Univ Nijmegen Med Ctr, Dept Cognit Neurosci, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands. [Brouwer, Rachel M.; Pol, Hilleke E. Hulshoff; Kahn, Rene S.; Mandl, Rene; Ophoff, Roel A.; Schnack, Hugo G.; Schuer, Remmelt; Van den Heuvel, Martijn; van Haren, Neeltje E. M.] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Utrecht, Netherlands. [Buckner, Randy L.; Fagerness, Jesen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Buitelaar, Jan] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands. [Bulayeva, Kazima] Russian Acad Sci, NI Vavilov Inst Gen Genet, Moscow 119991, Russia. [Bustillo, Juan R.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Cannon, Dara M.; Donohoe, Gary; Emsell, Louise; McDonald, Colm; Scanlon, Cathy] Natl Univ Ireland Galway, Clin Neuroimaging Lab, Galway, Ireland. [Cantor, Rita M.; Fears, Scott; Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. [Chakravarty, M. Mallar] Ctr Addict & Mental Hlth, Kimel Family Translat Imaging Genet Lab, Toronto, ON, Canada. [Christoforou, Andrea; Le Hellard, Stephanie; Steen, Vidar M.] Univ Bergen, Dept Clin Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway. [Giddaluru, Sudheer] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, N-5021 Bergen, Norway. [Muehleisen, Thomas W.] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany. [Cichon, Sven; Muehleisen, Thomas W.] Univ Bonn, Inst Human Genet, Bonn, Germany. [Cichon, Sven; Muehleisen, Thomas W.] Forschungszentrum Julich, Inst Neurosci & Med INM 1, D-52425 Julich, Germany. [Cichon, Sven] Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland. [Crespo-Facorro, Benedicto; Roiz-Santianez, Roberto; Tordesillas-Gutierrez, Diana] Univ Cantabria, Sch Med, Dept Psychiat, Marques de Valdecilla Univ Hosp,IFIMAV, E-39005 Santander, Spain. [Crespo-Facorro, Benedicto; Roiz-Santianez, Roberto; Tordesillas-Gutierrez, Diana] Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain. [Lopez, Lorna M.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Depondt, Chantal; Pandolfo, Massimo] Univ Libre Bruxelles, Dept Neurol, Hop Erasme, B-1070 Brussels, Belgium. [de Zubicaray, Greig I.] Univ Queensland, Sch Psychol, Brisbane, Qld 4072, Australia. [Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway. [Donohoe, Gary; Kelly, Sinead; Morris, Derek W.] Univ Dublin Trinity Coll, Neuropsychiat Genet Res Grp, Dept Psychiat, Inst Mol Med, Dublin 2, Ireland. [Donohoe, Gary; Kelly, Sinead; Morris, Derek W.] Univ Dublin Trinity Coll, Inst Neurosci, Dublin 2, Ireland. [Ehrlich, Stefan; Gollub, Randy L.; Hollinshead, Marisa; Holmes, Avram J.; Manoach, Dara S.] Massachusetts Gen Hosp, MGH HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ehrlich, Stefan; Hass, Johanna] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Univ Hosp CG Carus, Dresden, Germany. [Erk, Susanne; Heinz, Andreas; Mohnke, Sebastian; Romanczuk-Seiferth, Nina; Walter, Henrik] Charite, Dept Psychiat & Psychotherapy, Charite Campus Mitte, D-13353 Berlin, Germany. [Espeseth, Thomas; Westlye, Lars T.] Univ Oslo, Dept Psychol, Oslo, Norway. [Fisher, Simon E.; Francks, Clyde; Guadalupe, Tulio] Max Planck Inst Psycholinguist, NL-6500 AH Nijmegen, Netherlands. [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 Ctr, San Antonio, TX USA. [Frouin, Vincent] CEA, Neurospin, Paris, France. [Gollub, Randy L.; Holmes, Avram J.; Lee, Phil H.; Manoach, Dara S.; Roffman, Joshua L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Grabe, Hans J.; Wittfeld, Katharina] Ernst Moritz Arndt Univ Greifswald, German Ctr Neurodegenerat Dis DZNE, Greifswald, Germany. [Grimm, Oliver; Meyer-Lindenberg, Andreas; Rietschel, Marcella] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany. [Gruber, Oliver; Kraemer, Bernd; Trost, Sarah; Zilles, David] Univ Gottingen, Ctr Translat Res Syst Neurosci & Psychiat, Dept Psychiat, Gottingen, Germany. [Bois, Catherine; Dimitrova, Rali; Hagenaars, Saskia; Hall, Geoffrey B.; Lawrie, Stephen M.; McIntosh, Andrew M.; Papalampropoulou-Tsiridou, Melina; Papmeyer, Martina; Sussmann, Jessika; Whalley, Heather C.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland. [Hardy, John; Ryten, Mina; Trabzuni, Daniah] UCL Inst, Dept Mol Neurosci, London, England. [Hegenscheid, Katrin; Hosten, Norbert] Ernst Moritz Arndt Univ Greifswald, Dept Diagnost Radiol & Neuroradiol, Greifswald, Germany. [Hartman, Catharina A.; Hoekstra, Pieter J.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Homuth, Georg; Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Johnston, Caroline] South London & Maudsley Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res Biomed Res, Ctr Mental Hlth, London, England. [Johnston, Caroline] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Agartz, Ingrid; Ekman, Carl Johan; Joensson, Erik G.; Liberg, Benny] Karolinska Hosp & Inst, Dept Clin Neurosci, Stockholm, Sweden. [Kasperaviciute, Dalia; Matarin, Mar; Sisodiya, Sanjay M.] UCL Inst Neurol, Dept Clin & Expt Epilepsy, London, England. [Shen, Li] Indiana Univ Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA. [Kim, Sungeun; Nho, Kwangsik; Risacher, Shannon L.; Saykin, Andrew J.; Shen, Li] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Neuroimaging, Indianapolis, IN 46202 USA. [Hong, L. Elliot; Kochunov, Peter] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Brohawn, David G.; Fagerness, Jesen; Lee, Phil H.; Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Liu, Xinmin; McMahon, Francis J.; Woldehawariat, Girma] NIMH, Mood & Anxiety Disorders Sect, Human Genet Branch, Intramural Res Program,NIH,US Dept HHS, Bethesda, MD 20892 USA. [Liu, Xinmin] Columbia Univ Med Ctr, Taub Inst Res Alzheimer Dis & Aging Brain, New York, NY USA. [Schumann, Gunter; Delvecchio, Giuseppe; Dima, Danai; Loth, Eva] Kings Coll London, Inst Psychiat, MRC SGDP Ctr, London WC2R 2LS, England. [Macciardi, Fabio; Potkin, Steven G.; Rasmussen, Jerod; van Erp, Theo G. M.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Mather, Karen A.; Sachdev, Perminder S.; Wen, Wei] Univ New South Wales Med, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. [Mattheisen, Manuel] Aarhus Univ, Dept Biomed, Aarhus, Denmark. [Mattheisen, Manuel] Univ Bonn, Dept Genom Math, Bonn, Germany. [Mattingsdal, Morten] Sorlandet Hosp HF, Res Unit, Kristiansand, Norway. [McMahon, Katie L.] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia. [Meisenzahl, Eva] Univ Munich, Munich, Germany. [Penninx, Brenda W.; Schmaal, Lianne; Veltman, Dick J.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat & Neurosci, Amsterdam, Netherlands. [Moses, Eric K.] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Perth, WA 6009, Australia. [Mueller, Bryon A.; Schulz, S. Charles; Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Med Ctr, Minneapolis, MN 55455 USA. [Nilsson, Lars-Goeran] Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden. [Nyberg, Lars; Salami, Alireza] Umea Univ, Umea Ctr Funct Brain Imaging UFBI, Umea, Sweden. [Olvera, Rene L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Paus, Tomas] Univ Toronto, Rotman Res Inst, Toronto, ON, Canada. [Pausova, Zdenka] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [van der Wee, Nic J.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [van der Wee, Nic J.] Leiden Univ, Med Ctr, Leiden Inst Brain & Cognit, Leiden, Netherlands. [Ramasamy, Adaikalavan; Ryten, Mina; Weale, Michael E.] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England. [Sachdev, Perminder S.] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia. [Savitz, Jonathan] Laureate Inst Brain Res, Tulsa, OK USA. [Foroud, Tatiana; Saykin, Andrew J.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Seidman, Larry] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Simmons, Andrew] Kings Coll London, Inst Psychiat, Dept Neuroimaging, London WC2R 2LS, England. [Simmons, Andrew] Kings Coll London, NIHR Biomed Res Ctr Mental Hlth, South London & Maudsley NHS Trust, London WC2R 2LS, England. [Simmons, Andrew] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Sponheim, Scott R.] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA. [van Tol, Marie-Jose] Univ Groningen, Univ Med Ctr Groningen, Behav & Cognit Neurosci Neuroimaging Ctr, NL-9713 AV Groningen, Netherlands. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [White, Tonya] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. [Rijpkema, Mark; Zwiers, Marcel P.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, NL-6525 ED Nijmegen, Netherlands. [Jenkinson, Mark; Winkler, Anderson M.] Univ Oxford, Oxford Ctr Funct MRI Brain FMRIB, Oxford, England. [Kwok, John B. J.; Schofield, Peter R.] Neurosci Res Australia, Sydney, NSW, Australia. [Kwok, John B. J.; Schofield, Peter R.] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia. [Buckner, Randy L.; Hollinshead, Marisa; Holmes, Avram J.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Hatton, Sean N.; Hickie, Ian B.; Lagopoulos, Jim] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2006, Australia. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Walker, Robert] Univ Edinburgh, Ctr Regenerat Med, Edinburgh, Midlothian, Scotland. [Bastin, Mark E.; Smith, Colin] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland. [de Haan, Lieuwe; Koenders, Laura; Machielsen, Marise W. J.] UvA, Acad Psychiat Ctr, AMC, Dept Early Psychosis, Amsterdam, Netherlands. [Boomsma, Dorret I.; de Geus, Eco J. C.; Milaneschi, Yuri; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands. [Schork, Andrew J.] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA USA. [Haukvik, Unn K.] Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway. [Oosterlaan, Jaap] Vrije Univ Amsterdam, Dept Clin Neuropsychol, Amsterdam, Netherlands. [Ramasamy, Adaikalavan] UCL Inst Neurol, Reta Lila Weston Inst, London, England. [Ramasamy, Adaikalavan] UCL Inst Neurol, Dept Mol Neurosci, London, England. [Alhusaini, Saud] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada. [Almeida, Jorge; Phillips, Mary; Versace, Amelia] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Alda, Martin; Hajek, Tomas] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada. [Godlewska, Beata] Univ Oxford, Dept Psychiat, Oxford, England. [Mwangi, Benson; Soares, Jair C.] Univ Texas Med Sch, Dept Psychiat & Behav Sci, Houston, TX USA. [Mwangi, Benson] UT Med Sch, Dept Psychiat, Univ Texas Ctr Excellence Mood Disorders, Houston, TX USA. [Bearden, Carrie E.; Coppola, Giovanni; Fears, Scott] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Bearden, Carrie E.; Coppola, Giovanni; Fears, Scott] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA. [Milaneschi, Yuri] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA. [Walter, Henrik] Humboldt Univ, Berlin Sch Mind & Brain, D-10099 Berlin, Germany. [Bauer, Michael; Pfennig, Andrea] Carl Gustav Carus Univ Hosp, Dept Psychiat & Psychotherapy, Dresden, Germany. [Grabe, Hans J.] Helios Hosp Stralsund, Dept Psychiat & Psychotherapy, Stralsund, Germany. [Seidman, Larry] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Almeida, Jorge] Brown Univ, Dept Psychiat, Providence, RI 02912 USA. [Frangou, Sophia] Mt Sinai Sch Med, Psychosis Res Unit, New York, NY USA. [Strakowski, Stephen] Univ Cincinnati, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA. [Gur, Raquel E.; Gur, Ruben C.; Satterthwaite, Theodore D.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Gur, Ruben C.] Philadelphia Vet Adm Med Ctr, Philadelphia, PA USA. [Frey, Eva Maria; Frodl, Thomas] Univ Regensburg, Dept Psychiat & Psychotherapy, D-93053 Regensburg, Germany. [Frodl, Thomas] Univ Dublin, Trinity Coll, Dept Psychiat & Psychotherapy, Dublin, Germany. [Nilsson, Lars-Goeran] Univ Dublin, Trinity Coll, Dept Psychiat & Psychotherapy, Dublin, Germany. [Turner, Jessica] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Turner, Jessica] Georgia State Univ, Neurosci Inst, Atlanta, GA 30303 USA. [Hall, Geoffrey B.] McMaster Univ, Dept Psychol Neurosci & Behav, Hamilton, ON, Canada. [Clark, Vincent P.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Boen, Erlend; Elvsashagen, Torbjorn; Malt, Ulrik F.] Oslo Univ Hosp, Dept Psychosomat Med, Oslo, Norway. [Agartz, Ingrid; Bergmann, Orjan; Boen, Erlend; Elvsashagen, Torbjorn; Malt, Ulrik F.] Univ Oslo, Inst Clin Med, Oslo, Norway. [Risacher, Shannon L.] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA. [Pike, G. Bruce] Univ Calgary, Dept Radiol, Calgary, AB, Canada. [Nichols, Thomas E.] Univ Warwick, Dept Stat, Coventry CV4 7AL, W Midlands, England. [Nichols, Thomas E.] Univ Warwick, Warwick Mfg Grp, Coventry CV4 7AL, W Midlands, England. [Alpert, Kathryn; Wang, Lei] Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. [Alpert, Kathryn; Wang, Lei] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. [Landman, Bennett A.] Vanderbilt Univ, Nashville, TN 37235 USA. [Nugent, Allison C.] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. [Nauck, Matthias] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Landen, Mikael] Univ Gothenburg, Inst Neurosci & Physiol, Gothenburg, Sweden. [Landen, Mikael] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Chakravarty, M. Mallar] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON, Canada. [Savitz, Jonathan] Univ Tulsa, Fac Community Med, Tulsa, OK 74104 USA. [Laje, Gonzalo] Maryland Inst Neurosci & Dev MIND, Chevy Chase, MD USA. [MacQueen, Glenda M.] Univ Calgary, Hotchkiss Brain Inst, Mathison Ctr Mental Hlth Res & Educ, Calgary, AB, Canada. [Mueller-Myhsok, Bertram] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Caseras, Xavier] Cardiff Univ, Inst Psychol Med & Clin Neurosci, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales. [Hall, Jeremy] Cardiff Univ, Neurosci & Mental Hlth Res Inst, Cardiff CF10 3AX, S Glam, Wales. [Kwok, John B. J.] Univ New S Wales, Sch Med Sci, Kensington, NSW 2033, Australia. [Hwang, Kristy S.] Oakland Univ, William Beaumont Sch Med, Rochester, MI 48063 USA. [Conrod, Patricia] CHU St Justine Univ Hosp Res Ctr, Montreal, PQ, Canada. [Conrod, Patricia] Kings Coll London, Kings Hlth Partners, Addict Dept, London WC2R 2LS, England. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Lemaitre, Herve; Martinot, Jean-Luc] Paris Descartes Univ, Univ Paris 11, INSERM, CEA,Fac Med,Res Unit 1000,SHFJ Orsay,Maison de So, Paris, France. [Trabzuni, Daniah] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia. [van Eijk, Kristel] Univ Med Ctr Utrecht, Rudolf Magnus Inst, Dept Psychiat, Utrecht, Netherlands. [Armstrong, Nicola J.] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia. [Lourdusamy, Anbarasu] Univ Nottingham, Sch Med, Nottingham, England. [Chang, Kiki D.] Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. [Salami, Alireza] Karolinska Inst, Aging Res Ctr, Stockholm, Sweden. [Salami, Alireza] Stockholm Univ, S-10691 Stockholm, Sweden. [Poline, Jean-Baptiste] Univ Calif Berkeley, Brain Imaging Ctr, Hellen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Lauriello, John] Univ Missouri, Dept Psychiat, Columbia, MO 65201 USA. [Pearlson, Godfrey D.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Pearlson, Godfrey D.] Yale Univ, Dept Neurobiol, Sch Med, New Haven, CT USA. [Jack, Clifford R., Jr.] Mayo Clin, Rochester, MN USA. [Rose, Emma J.] RTI Int, Transdisciplinary & Translat Prevent Program, Baltimore, MD USA. [Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Goldstein, Rita Z.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY USA. [Rujescu, Dan] Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany. [Bockholt, Henry J.] Adv Biomed Informat Grp Llc, Iowa City, IA USA. [Stein, Jason L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, Los Angeles, CA 90095 USA. [Medland, Sarah E.; Renteria, Miguel E.; Wright, Margaret J.; Martin, Nicholas G.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Macciardi, Fabio] Univ Milan, Dept Pharmacol & Biomol Sci, I-20122 Milan, Italy. [Steen, Vidar M.] Haukeland Hosp, Ctr Med Genet & Mol Med, Dr E Martens Res Grp Biol Psychiat, N-5021 Bergen, Norway. [Garavan, Hugh] UHC Univ Vermont, Dept Psychiat, Burlington, VT USA. [Thalamuthu, Anbupalam] UNSW, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. [Freimer, Nelson B.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA. [Lawrence, Natalia S.] Univ Exeter, Sch Psychol, Exeter, Devon, England. [Drevets, Wayne] Johnson & Johnson Inc, Janssen Res & Dev, Titusville, NJ 08560 USA. RP Thompson, PM (reprint author), Univ So Calif, Imaging Genet Ctr, Inst Neuroimaging & Informat, Keck Sch Med, 2001 N Soto St, Los Angeles, CA 90033 USA. EM pthomp@usc.edu; wdrevets@its.jnj.com RI Nyberg, Lars/C-2514-2009; Weale, Michael/F-2587-2010; de Zubicaray, Greig/B-1763-2008; Walter, Henrik/O-2612-2013; Bralten, Janita/D-4647-2011; Hoogman, Martine/G-8958-2015; Roiz-Santianez, Roberto/H-6462-2015; Tordesillas-Gutierrez, Diana/H-6893-2015; Turner, Jessica/H-7282-2015; Rijpkema, Mark/D-1974-2010; Zwiers, Marcel/D-2968-2009; Alda, Martin/F-5812-2010; Cavalleri, Gianpiero/A-6632-2010; Rose, Emma/A-9960-2010; Brunner, Han/C-9928-2013; Hoekstra, Pieter/O-4396-2014; Savitz, Jonathan/C-3088-2009; Fox, Peter/B-4725-2010; Fisher, Simon/E-9130-2012; Ho, Beng-Choon/D-6959-2011; Lourdusamy, Anbarasu/P-6606-2014; Franke, Barbara/D-4836-2009; Ramasamy, Adaikalavan/G-2632-2010; Medland, Sarah/C-7630-2013; Jack, Clifford/F-2508-2010; Simmons, Andrew/B-8848-2008; Pike, Bruce/K-5562-2014; Binder, Elisabeth/K-8905-2014; Hardy, John/C-2451-2009; Laje, Gonzalo/L-2654-2014; McDonald, Colm/C-1430-2009; Dima, Danai/H-4342-2014; Hulshoff Pol, Hilleke/B-4795-2014; Munoz Maniega, Susana/I-8730-2014; Fernandez, Guillen/B-3771-2009; Montgomery, Grant/B-7148-2008; Mattheisen, Manuel/B-4949-2012; Wright, Margaret/A-4560-2016; Arias Vasquez, Alejandro/E-4762-2012; McMahon, Katie/C-6440-2009; Macciardi, Fabio/N-3768-2014; Frodl, Thomas/D-8118-2012; Li, Chiang-Shan/J-2813-2016; Matarin, Mar/F-1771-2016; Melle, Ingrid /B-4858-2011; Karen, Mather/O-9795-2016; Putz, Benno/P-2630-2016; Delvecchio, Giuseppe/J-7721-2016; Trabzuni, Daniah/C-4034-2012; Winkler, Anderson/P-7773-2016; Luciano, Michelle/F-7277-2010; Meyer-Lindenberg, Andreas/H-1076-2011; Clark, Vincent/B-3343-2010; Almeida, Jorge/O-5185-2014; OI Cavalleri, Gianpiero/0000-0002-9802-0506; Jonsson, Erik/0000-0001-8368-6332; Donohoe, Gary/0000-0003-3037-7426; Sachdev, Perminder/0000-0002-9595-3220; Mwangi, Benson/0000-0002-1717-4395; Shen, Li/0000-0002-5443-0503; Schur, Remmelt/0000-0002-2840-2592; Hatton, Sean/0000-0002-9149-8726; Westlye, Lars T./0000-0001-8644-956X; de Geus, Eco/0000-0001-6022-2666; Martin, Nicholas/0000-0003-4069-8020; McIntosh, Andrew/0000-0002-0198-4588; Nyberg, Lars/0000-0002-3367-1746; Weale, Michael/0000-0003-4593-1186; de Zubicaray, Greig/0000-0003-4506-0579; Hoogman, Martine/0000-0002-1261-7628; Roiz-Santianez, Roberto/0000-0002-5176-2983; Tordesillas-Gutierrez, Diana/0000-0003-1458-3932; Turner, Jessica/0000-0003-0076-8434; Rijpkema, Mark/0000-0002-8495-4703; Zwiers, Marcel/0000-0001-5483-2935; Alda, Martin/0000-0001-9544-3944; Rose, Emma/0000-0001-5365-4794; Savitz, Jonathan/0000-0001-8143-182X; Fox, Peter/0000-0002-0465-2028; Fisher, Simon/0000-0002-3132-1996; Ho, Beng-Choon/0000-0003-3976-1555; Franke, Barbara/0000-0003-4375-6572; Ramasamy, Adaikalavan/0000-0002-7598-2892; Medland, Sarah/0000-0003-1382-380X; Jack, Clifford/0000-0001-7916-622X; Simmons, Andrew/0000-0003-2306-5811; Pike, Bruce/0000-0001-8924-683X; Laje, Gonzalo/0000-0003-2763-3329; Dima, Danai/0000-0002-2598-0952; Hulshoff Pol, Hilleke/0000-0002-2038-5281; Munoz Maniega, Susana/0000-0001-5185-6384; Fernandez, Guillen/0000-0002-5522-0604; Montgomery, Grant/0000-0002-4140-8139; Mattheisen, Manuel/0000-0002-8442-493X; Wright, Margaret/0000-0001-7133-4970; Arias Vasquez, Alejandro/0000-0002-4786-0169; McMahon, Katie/0000-0002-6357-615X; Macciardi, Fabio/0000-0003-0537-4266; Li, Chiang-Shan/0000-0002-9393-1212; Matarin, Mar/0000-0002-4717-5735; Melle, Ingrid /0000-0002-9783-548X; Karen, Mather/0000-0003-4143-8941; Putz, Benno/0000-0002-2208-209X; Delvecchio, Giuseppe/0000-0003-4750-1980; Jenkinson, Mark/0000-0001-6043-0166; Gollub, Randy L./0000-0002-9434-4044; McMahon, Francis/0000-0002-9469-305X; Cannon, Dara/0000-0001-7378-3411; Agartz, Ingrid/0000-0002-9839-5391; Kwok, John/0000-0001-9574-6195; Lourdusamy, Anbarasu/0000-0002-1978-6301; Morris, Derek/0000-0002-3413-570X; Andreassen, Ole A./0000-0002-4461-3568; Romanczuk-Seiferth, Nina/0000-0002-6931-269X; Emsell, Louise/0000-0003-0011-4158; Potkin, Steven/0000-0003-1028-1013; Nugent, Allison/0000-0003-2569-2480; Trabzuni, Daniah/0000-0003-4826-9570; Stein, Jason/0000-0003-4829-0513; Frodl, Thomas/0000-0002-8113-6959; Lawrence, Natalia/0000-0003-1969-6637; Caseras, Xavier/0000-0002-8490-6891; Winkler, Anderson/0000-0002-4169-9781; Luciano, Michelle/0000-0003-0935-7682; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Clark, Vincent/0000-0002-9151-2102; Almeida, Jorge/0000-0002-1213-1986; Bulayeva, Kazima/0000-0003-4830-5383; Lemaitre, Herve/0000-0002-5952-076X; Toro, Roberto/0000-0002-6671-858X; van den Heuvel, Martijn/0000-0003-1570-1195; Whelan, Christopher/0000-0003-0308-5583 FU Biotechnology and Biological Sciences Research Council [BB/F019394/1]; Medical Research Council [G0701120, G0600429, G0700704, G0802462, G0901254, G1001245, MR/J006742/1, MR/K01417X/1, MR/K026992/1, MR/L010305/1, MR/L016400/1]; NCATS NIH HHS [UL1 TR001108]; NIA NIH HHS [P30 AG010133, P50 AG005134, R01 AG019771, R01 AG040770, U01 AG024904, U19 AG010483, U24 AG021886]; NIBIB NIH HHS [P41 EB015922, R01 EB005846, R01 EB015611, U54 EB020403]; NIMH NIH HHS [K01 MH099232, K99 MH101367]; NLM NIH HHS [K99 LM011384, R00 LM011384, R01 LM011360]; Parkinson's UK [G-0907]; Wellcome Trust [100309, 104036] NR 195 TC 84 Z9 85 U1 9 U2 82 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1931-7557 EI 1931-7565 J9 BRAIN IMAGING BEHAV JI Brain Imaging Behav. PD JUN PY 2014 VL 8 IS 2 SI SI BP 153 EP 182 DI 10.1007/s11682-013-9269-5 PG 30 WC Neuroimaging SC Neurosciences & Neurology GA AG9UP UT WOS:000335765700003 PM 24399358 ER PT J AU Cohen, MG Ghatak, A Kleiman, NS Naidu, SS Massaro, JM Kirtane, AJ Moses, J Ohman, EM Dzavik, V Palacios, IF Heldman, AW Popma, JJ O'Neill, WW AF Cohen, Mauricio G. Ghatak, Abhijit Kleiman, Neal S. Naidu, Srihari S. Massaro, Joseph M. Kirtane, Ajay J. Moses, Jeffrey Ohman, E. Magnus Dzavik, Vladimir Palacios, Igor F. Heldman, Alan W. Popma, Jeffrey J. O'Neill, William W. TI Optimizing Rotational Atherectomy in High-Risk Percutaneous Coronary Interventions: Insights from the PROTECT II Study SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE atherectomy; percutaneous coronary intervention; ventricular support device ID INTRAAORTIC BALLOON PUMP; MYOCARDIAL-INFARCTION; HEMODYNAMIC SUPPORT; TASK-FORCE; FOLLOW-UP; REVASCULARIZATION; ASSOCIATION; GUIDELINES; ELEVATION; OUTCOMES AB ObjectiveTo study rotational atherectomy (RA) outcomes in patients undergoing high-risk PCI randomized to receive hemodynamic support using either IABP or Impella 2.5 in the PROTECT II trial. BackgroundRA of heavily calcified lesions is often necessary for complex PCI but can be associated with slow-flow, hypotension, and higher risk of periprocedural MI. MethodsWe compared baseline, angiographic, procedural characteristics, and outcomes of patients treated with and without RA. We examined also RA technique and outcomes. ResultsRA was used in 52 of 448 patients (32 with Impella vs 20 with IABP, P=0.08). RA patients were older (72 vs. 67 yo, P=0.0009), more likely to have prior CABG (48 vs. 32%, P=0.017), higher STS (8.1 vs. 5.7, P=0.012) and higher SYNTAX scores (37 vs. 29, P<0.0001). At 90 days, RA use was associated with higher incidence of MI but no mortality difference. RA was used more aggressively with Impella resulting in higher rate of periprocedural MI (P<0.01), with no difference in mortality between groups (P=0.78). Repeat revascularization occurred less frequently with Impella (P<0.001). There were no differences in 90-day major adverse events between IABP and Impella in patients undergoing RA (P=0.29). In patients not treated with RA, fewer MAEs were observed with Impella compared with IABP (P=0.03). ConclusionsPatients who were treated with RA had more comorbidities, and more complex and extensive coronary artery disease. In patients with Impella, more aggressive RA use resulted in fewer revascularization events but higher incidence of periprocedural MI. (c) 2013 Wiley Periodicals, Inc. C1 [Cohen, Mauricio G.; Ghatak, Abhijit; Heldman, Alan W.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Kleiman, Neal S.] Methodist DeBakey Heart & Vasc Inst, Houston, TX USA. [Naidu, Srihari S.] Winthrop Univ Hosp, New York, NY USA. [Massaro, Joseph M.] Harvard Clin Res Inst, Boston, MA USA. [Kirtane, Ajay J.; Moses, Jeffrey] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Ohman, E. Magnus] Duke Univ, Med Ctr, Durham, NC USA. [Dzavik, Vladimir] Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada. [Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Popma, Jeffrey J.] Beth Israel Med Deaconess Harvard Med Sch, Boston, MA USA. [O'Neill, William W.] Henry Ford Hosp, Detroit, MI 48202 USA. RP Cohen, MG (reprint author), Univ Miami Hosp, 1400 NW 12 th Ave,Suite 1179, Miami, FL 33136 USA. EM mgcohen@med.miami.edu OI Cohen, Mauricio/0000-0003-2038-6070 FU Abiomed, Inc. FX Contract grant sponsor: Abiomed, Inc. NR 28 TC 9 Z9 9 U1 0 U2 4 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 JUN 1 PY 2014 VL 83 IS 7 BP 1057 EP 1064 DI 10.1002/ccd.25277 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA AH2LV UT WOS:000335953900018 PM 24174321 ER PT J AU Shenouda, MN Sadek, BT Goldberg, SI Keruakous, AR Croft, BJ Raad, RFA Taghian, AG AF Shenouda, Mina N. Sadek, Betro T. Goldberg, Saveli I. Keruakous, Amany R. Croft, Brandon J. Raad, Rita F. Abi Taghian, Alphonse G. TI Clinical Outcome of Isolated Locoregional Recurrence in Patients With Breast Cancer According to Their Primary Local Treatment SO CLINICAL BREAST CANCER LA English DT Article DE Breast cancer; Isolated locoregional recurrence; Local breast treatment; Long-term clinical outcome Prognostic variables ID CONSERVATIVE SURGERY; REGIONAL RECURRENCE; TUMOR RECURRENCE; CONSERVING TREATMENT; RANDOMIZED-TRIALS; SYSTEMIC THERAPY; FOLLOW-UP; MASTECTOMY; PROGNOSIS; RADIATION AB The long-term clinical outcome was studied for 220 patients with breast cancer who developed isolated locoregional recurrence. Based on a multivariate analysis including multiple pathologic and clinical parameters, the results suggest that patients who had breast-conserving surgery and radiation therapy for their primary tumor have a significantly better clinical outcome compared with those who had mastectomy with no radiation therapy. Introduction: This study assessed the clinical outcome and prognostic factors in patients with breast cancer who presented with isolated locoregional recurrence (ILRR) as a first event. Materials and Methods: Between 1970 and 2008, 2960 patients with pT1-2, N0-3, M0 primary invasive breast cancer had either breast-conserving therapy (BCT) using lumpectomy and radiation therapy (RT) (group A = 1849 patients) or mastectomy without RT (group B = 1111 patients). Out of groups A and B, 117 and 103 patients, respectively, developed ILRR as a first event. Those 220 patients served as the basis for this study. A multivariate analysis was performed to estimate the clinical outcome of both groups, taking into account clinically relevant variables for the primary tumor and ILRR. Results: The median follow-up after ILRR was 83 months. The median disease-free interval (DFI) was 79 and 38 months for groups A and B, respectively. The overall survival (OS) for group A was 81% and 69% at 5 and 8 years, respectively. For group B, it was 61% and 46%, respectively. The distant metastasis-free survival (DMFS) for group A was 84% at 5 years and remained 84% at 8 years. The DMFS for group B was 60% at 5 years and 52% at 8 years. In multivariate analysis, initial local treatment (BCT vs. mastectomy without RT), pathologic T stage, locoregional recurrence site (local vs. regional), and DFI (<= 4 years vs. > 4 years) were significant prognostic variables for both OS and DMFS. Conclusion: Patients with breast cancer who developed ILRR after BCT as their initial local treatment have better clinical outcome compared with those who had mastectomy without RT. (C) 2014 Elsevier Inc. All rights reserved. C1 [Shenouda, Mina N.; Sadek, Betro T.; Goldberg, Saveli I.; Keruakous, Amany R.; Croft, Brandon J.; Raad, Rita F. Abi; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Goldberg, Saveli I.] Massachusetts Gen Hosp, Stat Sect, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 3 Bldg,100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 FU National Cancer Institute [R01CA139118, P50CA089393] FX This project was supported by Award Number R01CA139118 (AGT) and Award Number P50CA089393 (AGT) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Cancer Institute or the National Institutes of Health. All authors state that they have no conflicts of interest. NR 33 TC 3 Z9 3 U1 0 U2 3 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 EI 1938-0666 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD JUN PY 2014 VL 14 IS 3 BP 198 EP 204 DI 10.1016/j.clbc.2013.12.007 PG 7 WC Oncology SC Oncology GA AH3JM UT WOS:000336019500008 PM 24485702 ER PT J AU Matulis, S Resick, PA Rosner, R Steil, R AF Matulis, Simone Resick, Patricia A. Rosner, Rita Steil, Regina TI Developmentally Adapted Cognitive Processing Therapy for Adolescents Suffering from Posttraumatic Stress Disorder after Childhood Sexual or Physical Abuse: A Pilot Study SO CLINICAL CHILD AND FAMILY PSYCHOLOGY REVIEW LA English DT Article DE Posttraumatic stress; Sexual abuse; Physical abuse; Adolescents ID RANDOMIZED-CONTROLLED-TRIAL; BORDERLINE PERSONALITY-DISORDER; DIALECTICAL BEHAVIOR-THERAPY; ADMINISTERED PTSD SCALE; LONG-TERM SEQUELAE; CLINICAL-TRIAL; PSYCHOMETRIC PROPERTIES; INTERRATER RELIABILITY; PROLONGED EXPOSURE; ASSAULT VICTIMS AB Although childhood sexual abuse and childhood physical abuse (CSA and CPA) have severe psychopathological consequences, there is little evidence supporting psychotherapeutic interventions for adolescents who have experienced CSA or CPA. To provide a treatment tailored to the specific needs of adolescents suffering from abuse-related posttraumatic stress disorder (PTSD), we modified Cognitive Processing Therapy (CPT) by adding new treatment modules and changing the therapy setting. To evaluate the feasibility and efficacy of Developmentally Adapted CPT (D-CPT), we treated 12 adolescents suffering from PTSD secondary to CSA or CPA. Patients were assessed prior to treatment (t0), post-treatment (t1), and 6 weeks after treatment (t2). Assessments included the Clinician-Administered PTSD Scale (CAPS), the UCLA PTSD Index (UCLA), the Children's Depression Inventory (CDI), the Adolescent Dissociative Experiences Scale (A-DES), and the Borderline Symptom List (BSL-23). MANOVAs revealed that posttraumatic stress measurements and associated symptom measurements significantly differed across time points. When comparing t0 with t2, Cohen's d was large with respect to the CAPS scores (d = 1.45, p < .001) and the UCLA scores (d = 1.91, p < .001). Cohen's d had a medium magnitude with respect to the CDI scores (d = .78, p < .001), the A-DES scores (d = 0.64, p < .05), and the BSL-23 scores (d = 0.74, p < .01). D-CPT has the potential to reduce PTSD symptoms and comorbid psychopathology in adolescents with histories of CSA or CPA. C1 [Matulis, Simone; Steil, Regina] Goethe Univ Frankfurt, Inst Psychol, Dept Clin Psychol & Psychotherapy, D-60054 Frankfurt, Germany. [Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Resick, Patricia A.] Boston Univ, Boston, MA 02215 USA. [Rosner, Rita] Catholic Univ Eichstatt Ingolstadt, Eichstatt, Ingolstadt, Germany. RP Matulis, S (reprint author), Goethe Univ Frankfurt, Inst Psychol, Dept Clin Psychol & Psychotherapy, Postbox 11 19 32-120, D-60054 Frankfurt, Germany. EM matulis@psych.uni-frankfurt.de NR 112 TC 15 Z9 15 U1 3 U2 35 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1096-4037 EI 1573-2827 J9 CLIN CHILD FAM PSYCH JI Clin. Child Fam. Psychol. Rev. PD JUN PY 2014 VL 17 IS 2 BP 173 EP 190 DI 10.1007/s10567-013-0156-9 PG 18 WC Psychology, Clinical SC Psychology GA AH0NZ UT WOS:000335818200004 PM 24101403 ER PT J AU Bragg, DC Sharma, N AF Bragg, D. Cristopher Sharma, Nutan TI Update on Treatments for Dystonia SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Dystonia; Treatment; Medication; Deep brain stimulation ID DEEP-BRAIN-STIMULATION; CERVICAL DYSTONIA; BOTULINUM TOXIN; MOVEMENT-DISORDERS; TARDIVE DYSTONIA; TRIHEXYPHENIDYL; NEUROTOXIN; NEUROLOGY; EFFICACY; HISTORY AB Oral medication, botulinum toxin injections, and deep brain stimulation are the current mainstays of treatment for dystonia. In addition, physical and other supportive therapies may help prevent further complications (eg, contractures) and improve function. This review discusses evidence-based medical treatment of dystonia with an emphasis on recent advances in treatment. We will also review the current treatment approaches and suggest ways in which these therapies can be applied to individuals with dystonia. C1 [Bragg, D. Cristopher; Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sharma, N (reprint author), 149 13th St,Room 6407, Charlestown, MA 02129 USA. EM nsharma@partners.org FU Merz Pharmaceuticals; Allergan; NIH [NIH/NINDS P50NS037409]; American Academy of Neurology; Oakstone Publishing FX D. Cristopher Bragg declares that he has no conflict of interest. Nutan Sharma has received consultancy fees from Merz Pharmaceuticals and Allergan; a grant from NIH (NIH/NINDS P50NS037409); honorarium payment from The American Academy of Neurology; and payment for development of an educational presentation from Oakstone Publishing. NR 31 TC 3 Z9 3 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 EI 1534-6293 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD JUN PY 2014 VL 14 IS 6 AR 454 DI 10.1007/s11910-014-0454-8 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AG9FK UT WOS:000335724600007 PM 24744022 ER PT J AU Desai, NS Khandelwal, A Virmani, V Kwatra, NS Ricci, JA Saboo, SS AF Desai, Naman S. Khandelwal, Ashish Virmani, Vivek Kwatra, Neha S. Ricci, Joseph A. Saboo, Sachin S. TI Imaging in laparoscopic cholecystectomy-What a radiologist needs to know SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Review DE Laparoscopic cholecystectomy; Cholelithiasis; Biliary tract surgical procedure; Post-cholecystectomy syndrome ID BILIARY COMPLICATIONS; LIVER-TRANSPLANTATION; PERSONAL-EXPERIENCE; VASCULAR INJURIES; CYSTIC DUCT; MANAGEMENT; GALLBLADDER; MECHANISMS; GALLSTONES; SURGERY AB Laparoscopic cholecystectomy is the gold standard treatment option for cholelithiasis. In order to properly assess for the complications related to the procedure, an understanding of the normal biliary anatomy, its variants and the normal postoperative imaging is essential. Radiologist must be aware of benefits and limitations of multiple imaging modalities in characterizing the complications of this procedure as each of these modalities have a critical role in evaluating a symptomatic post-cholecystectomy patient. The purpose of this article is describe the multi-modality imaging of normal biliary anatomy and its variants, as well as to illustrate the imaging features of biliary, vascular, cystic duct, infectious as well as miscellaneous complications of laparoscopic cholecystectomy. We focus on the information that the radiologist needs to know about the radiographic manifestations of potential complications of this procedure. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Desai, Naman S.; Khandelwal, Ashish; Kwatra, Neha S.; Saboo, Sachin S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Virmani, Vivek] Dr Everett Chalmers Hosp, Dept Radiol, Fredericton, NB E3B 5N5, Canada. [Ricci, Joseph A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Khandelwal, A (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM nsdesai@partners.org; drashish83@gmail.com; drvivek.virmani@horizonnb.ca; nkwatra@partners.org; jaricci@partners.org; ssaboo@partners.org NR 46 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2014 VL 83 IS 6 BP 867 EP 879 DI 10.1016/j.ejrad.2014.02.016 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AH1UJ UT WOS:000335906400001 PM 24657107 ER PT J AU Citrome, L Karagianis, J Maguire, GA Nierenberg, AA AF Citrome, L. Karagianis, J. Maguire, G. A. Nierenberg, A. A. TI Pharmaism: a tale of two perspectives SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Editorial Material AB Linked Comment: . Linked Comment: . C1 [Citrome, L.] New York Med Coll, Valhalla, NY 10595 USA. [Karagianis, J.] Univ Toronto, Toronto, ON, Canada. [Karagianis, J.] Waypoint Ctr Mental Hlth Care, Penetanguishene, ON, Canada. [Maguire, G. A.] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. [Nierenberg, A. A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nierenberg, A. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Citrome, L (reprint author), New York Med Coll, Valhalla, NY 10595 USA. OI Citrome, Leslie/0000-0002-6098-9266 NR 3 TC 7 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1368-5031 EI 1742-1241 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD JUN PY 2014 VL 68 IS 6 BP 659 EP 661 DI 10.1111/ijcp.12460 PG 3 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA AH2JN UT WOS:000335947400001 PM 24837087 ER PT J AU Baldwin, MR Reid, MC Westlake, AA Rowe, JW Granieri, EC Wunsch, H Dam, TT Rabinowitz, D Goldstein, NE Maurer, MS Lederer, DJ AF Baldwin, Matthew R. Reid, M. Cary Westlake, Amanda A. Rowe, John W. Granieri, Evelyn C. Wunsch, Hannah Thuy-Tien Dam Rabinowitz, Daniel Goldstein, Nathan E. Maurer, Mathew S. Lederer, David J. TI The feasibility of measuring frailty to predict disability and mortality in older medical intensive care unit survivors SO JOURNAL OF CRITICAL CARE LA English DT Article DE Aged; Critically Ill; Frailty; Disability; Mortality ID PROLONGED MECHANICAL VENTILATION; CHRONIC CRITICAL ILLNESS; ACQUIRED WEAKNESS; FUNCTIONAL STATUS; RANDOMIZED-TRIAL; MUSCLE STRENGTH; SKELETAL-MUSCLE; CRITICALLY-ILL; ADULTS; OUTCOMES AB Purpose: To determine whether frailty can be measured within 4 days prior to hospital discharge in older intensive care unit (ICU) survivors of respiratory failure and whether it is associated with post-discharge disability and mortality. Materials and Methods: We performed a single-center prospective cohort study of 22 medical ICU survivors age 65 years or older who had received noninvasive or invasive mechanical ventilation for at least 24 hours. Frailty was defined as a score of >= 3 using Fried's 5-point scale. We measured disability with the Katz Activities of Daily Living. We estimated unadjusted associations between Fried's frailty score and incident disability at 1-month and 6-month mortality using Cox proportional hazard models. Results: The mean (SD) age was 77 (9) years, mean Acute Physiology and Chronic Health Evaluation II score was 27 (9.7), mean frailty score was 3.4 (1.3), and 18 (82%) were frail. Nine subjects (41%) died within 6 months, and all were frail. Each 1-point increase in frailty score was associated with a 90% increased rate of incident disability at 1-month (rate ratio: 1.9, 95% CI 0.7-4.9) and a threefold increase in 6-month mortality (rate ratio: 3.0, 95% CI 1.4-6.3). Conclusions: Frailty can be measured in older ICU survivors near hospital discharge and is associated with 6-month mortality in unadjusted analysis. Larger studies to determine if frailty independently predicts outcomes are warranted. (C) 2014 Elsevier Inc. All rights reserved. C1 [Baldwin, Matthew R.; Westlake, Amanda A.; Lederer, David J.] Columbia Univ, Coll Phys & Surg, Div Pulm & Crit Care, New York, NY USA. [Reid, M. Cary] Weill Cornell Med Ctr, Div Geriatr, New York, NY USA. [Rowe, John W.] Columbia Univ, Mailman Sch Publ Hlth, Dept Hlth Policy, New York, NY USA. [Granieri, Evelyn C.] Columbia Univ, Coll Phys & Surg, Div Geriatr Med & Aging, New York, NY USA. [Wunsch, Hannah; Thuy-Tien Dam; Lederer, David J.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Wunsch, Hannah] Columbia Univ, Coll Phys & Surg, Dept Anesthesiol, New York, NY USA. [Rabinowitz, Daniel] Columbia Univ, Dept Stat, New York, NY 10027 USA. [Goldstein, Nathan E.] Mt Sinai Sch Med, Div Geriatr & Palliat Med, New York, NY USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr, Clin Ctr, New York, NY USA. [Maurer, Mathew S.] Columbia Univ, Coll Phys & Surg, Div Cardiol, New York, NY USA. RP Baldwin, MR (reprint author), 622 W 168th St,PH-8,Room 101, New York, NY 10032 USA. EM mrb45@columbia.edu OI Reid, Cary/0000-0001-8117-662X FU National Institute on Aging (NIA) [3P30AG022845-078] FX The authors of this manuscript have no conflicts of interest to disclose as described by the Journal of Critical Care. This study was funded by a sub-contract pilot grant from grant 3P30AG022845-078 from the National Institute on Aging (NIA), and the NIA had no role in the study design, analysis, or manuscript approval. NR 51 TC 10 Z9 10 U1 5 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 EI 1557-8615 J9 J CRIT CARE JI J. Crit. Care PD JUN PY 2014 VL 29 IS 3 BP 401 EP 408 DI 10.1016/j.jcrc.2013.12.019 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA AH0OA UT WOS:000335818300016 PM 24559575 ER PT J AU Li, HY Yang, XJ Yang, GB Hong, Z Zhou, LY Yin, PQ Xiao, Y Chen, LY Chung, RT Zhang, LL AF Li, Hongyan Yang, Xiaojie Yang, Guangbo Hong, Zhi Zhou, Liya Yin, Peiqi Xiao, Yan Chen, Lingyi Chung, Raymond T. Zhang, Leiliang TI Hepatitis C Virus NS5A Hijacks ARFGAP1 To Maintain a Phosphatidylinositol 4-Phosphate-Enriched Microenvironment SO JOURNAL OF VIROLOGY LA English DT Article ID SECRETORY PATHWAY; RNA REPLICATION; PROTEIN; RECRUITMENT; PHOSPHATASE; TRANSPORT; COATOMER; PROMOTES; BINDING AB Phosphatidylinositol 4-phosphate (PI4P) is well known to be upregulated during hepatitis C virus (HCV) replication. The role of PI4 kinases in HCV has been extensively investigated. Whether the PI4P phosphatase Sac1 is altered by HCV remains unclear. Here, we identified ARFGAP1 to be a novel host factor for HCV replication. We further show that Sac1 interacts with ARFGAP1 and inhibits HCV replication. The elevation of PI4P induced by HCV NS5A is abrogated when the coatomer protein I (COPI) pathway is inhibited. We also found an interaction between NS5A and ARFGAP1. Furthermore, we identified a conserved cluster of positively charged amino acids in NS5A critical for interaction between NS5A and ARFGAP1, induction of PI4P, and HCV replication. Our data demonstrate that ARFGAP1 is a host factor for HCV RNA replication. ARFGAP1 is hijacked by HCV NS5A to remove COPI cargo Sac1 from the site of HCV replication to maintain high levels of PI4P. Our findings provide an additional mechanism by which HCV enhances formation of a PI4P-rich environment. C1 [Li, Hongyan; Yang, Xiaojie; Yang, Guangbo; Hong, Zhi; Zhou, Liya; Yin, Peiqi; Xiao, Yan; Zhang, Leiliang] Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China. [Li, Hongyan; Yang, Xiaojie; Yang, Guangbo; Hong, Zhi; Zhou, Liya; Yin, Peiqi; Xiao, Yan; Zhang, Leiliang] Peking Union Med Coll, Beijing 100021, Peoples R China. [Li, Hongyan; Chen, Lingyi] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China. [Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA USA. RP Zhang, LL (reprint author), Chinese Acad Med Sci, Inst Pathogen Biol, MOH Key Lab Syst Biol Pathogens, Beijing 100730, Peoples R China. EM zhangll@ipbcams.ac.cn FU National Natural Science Foundation of China [81271832]; Beijing Natural Science Foundation [7132140]; National Science and Technology Major Project of China [2013ZX10004-601]; Program for Changjiang Scholars and Innovative Research Team in University [IRT13007]; Youth Fund of PUMC [2012J03]; Fundamental Research Funds for the Central Universities; Research Fund for the Doctoral Program of Higher Education of China [20121106120058]; Intramural Research Program of the Institute of Pathogen Biology; CAMS [2012IPB101]; NIH [AI082630]; Rising Star of PUMC FX This work was supported by grants from the National Natural Science Foundation of China (81271832), the Beijing Natural Science Foundation (7132140), the National Science and Technology Major Project of China (2013ZX10004-601), the Program for Changjiang Scholars and Innovative Research Team in University (IRT13007), the Youth Fund of PUMC (2012J03), the Fundamental Research Funds for the Central Universities, Rising Star of PUMC, the Research Fund for the Doctoral Program of Higher Education of China (20121106120058), the Intramural Research Program of the Institute of Pathogen Biology, and the CAMS (2012IPB101) to L.Z. and the NIH (AI082630) to R.T.C. NR 36 TC 15 Z9 15 U1 2 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 JUN PY 2014 VL 88 IS 11 BP 5956 EP 5966 DI 10.1128/JVI.03738-13 PG 11 WC Virology SC Virology GA AH2SB UT WOS:000335970300006 PM 24623438 ER PT J AU Cagnetta, A Adamia, S Acharya, C Patrone, F Miglino, M Nencioni, A Gobbi, M Cea, M AF Cagnetta, Antonia Adamia, Sophia Acharya, Chirag Patrone, Franco Miglino, Maurizio Nencioni, Alessio Gobbi, Marco Cea, Michele TI Role of genotype-based approach in the clinical management of adult acute myeloid leukemia with normal cytogenetics SO LEUKEMIA RESEARCH LA English DT Review DE AML; Genomic heterogeneity; Prognosis; Mutations; Minimal residual disease ID MINIMAL RESIDUAL DISEASE; CYTOPLASMIC MUTATED NUCLEOPHOSMIN; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; AML STUDY-GROUP; TUMOR GENE WT1; CHRONIC MYELOMONOCYTIC LEUKEMIA; INTERMEDIATE-RISK KARYOTYPE; FAVORABLE PROGNOSTIC IMPACT; ISOCITRATE-DEHYDROGENASE 1 AB Acute myeloid leukemia (AML) is the most common form of acute leukemia affecting adults. Although it is a complex disease driven by numerous genetic and epigenetic abnormalities, nearly 50% of patients exhibit a normal karyotype (CNAML) with an intermediate cytogenetic risk. However, a widespread genomic analysis has recently shown the recurrence of genomic aberrations in this category (mutations of FLT3, CEBPA, NPM1, RUNX1, TET2, IDH1/2, DNMT3A, ASXL1, MLL and WT1) thus revealing its marked genomic heterogeneity. In this perspective, a global gene expression analysis of AML patients provides an independent prognostic marker to categorize each patient into clinicpathologic subgroups based on its molecular genetic defects. Consistently such classification, taking into account the uniqueness of each AML patient, furnishes an individualized treatment approach leading a step closer to personalized medicine. Overall the genomewide analysis of AML patients, by providing novel insights into biology of this tumor, furnishes accurate prognostic markers as well as useful tools for selecting the most appropriate treatment option. Moreover it provides novel therapeutic targets useful to enhance efficacy of the current antiAML therapeutics. Here we describe the prognostic relevance of such new genetic data and discuss how this approach can be used to improve survival and treatment of AML patients. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Cagnetta, Antonia; Adamia, Sophia; Acharya, Chirag; Cea, Michele] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cagnetta, Antonia; Patrone, Franco; Miglino, Maurizio; Nencioni, Alessio; Gobbi, Marco; Cea, Michele] IRCCS AOU San Martino IST, Dept Hematol & Oncol, Genoa, Italy. RP Cagnetta, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, M551,450 Brookline Ave, Boston, MA 02115 USA. EM antonia_cagnetta@dfci.harvard.edu; michele_cea@dfci.harvard.edu OI patrone, franco/0000-0003-4170-9131 FU Associazione Cristina Bassi; American-Italian Cancer Foundation; Fondazione Italiana perla Ricerca sul Cancro FX This study is supported by Associazione Cristina Bassi (A.C.), American-Italian Cancer Foundation and Fondazione Italiana perla Ricerca sul Cancro (M.C.). NR 175 TC 13 Z9 14 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 JUN PY 2014 VL 38 IS 6 BP 649 EP 659 DI 10.1016/j.leukres.2014.03.006 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA AH1YY UT WOS:000335919000001 PM 24726781 ER PT J AU Schilero, GJ Radulovic, M Wecht, JM Spungen, AM Bauman, WA Lesser, M AF Schilero, Gregory J. Radulovic, Miroslav Wecht, Jill M. Spungen, Ann M. Bauman, William A. Lesser, Marvin TI A Center's Experience: Pulmonary Function in Spinal Cord Injury SO LUNG LA English DT Review DE Spinal cord injury; Tetraplegia; Pulmonary function; Respiratory muscle function; Nonspecific airway hyperreactivity; Airway inflammation; Obstructive sleep apnea ID GASTROESOPHAGEAL-REFLUX DISEASE; OBSTRUCTIVE SLEEP-APNEA; AIR-FLOW OBSTRUCTION; RIB CAGE MOTION; BRONCHIAL HYPERRESPONSIVENESS; INDUCED BRONCHOCONSTRICTION; RESPIRATORY MECHANICS; TETRAPLEGIC SUBJECTS; IPRATROPIUM BROMIDE; VITAL CAPACITY AB Traumatic spinal cord injury (SCI) is associated with significant psychological and physical challenges. A multidisciplinary approach to management is essential to ensure recovery during the acute phase, and comprehensive rehabilitative strategies are necessary to foster independence and quality of life throughout the chronic phase of injury. Complications that beset these individuals are often a unique consequence of SCI, and knowledge of the effects of SCI upon organ systems is essential for appropriate management. According to the National SCI Statistical Center (NSCISC), as of 2010 there were an estimated 265,000 persons living with SCI in the United States, with approximately 12,000 incidence cases annually. Although life expectancy for newly injured individuals with SCI is markedly reduced, persons with chronic SCI are expected to live about as long as individuals without SCI; however, longevity varies inversely with level of injury. Since 2005, 56 % of persons with SCI are tetraplegic, and due to paralysis of respiratory muscles, these individuals may be especially prone to pulmonary complications, which remain a major cause of mortality among persons with chronic SCI. We at the VA Rehabilitation Research and Development Center of Excellence for the Medical Consequences of SCI at the James J. Peters VA Medical Center have devoted more than 25 years to the study of secondary medical conditions that complicate SCI. Herein, we review pulmonary research at the Center, both our past and future endeavors, which form an integral part of our multidisciplinary approach toward achieving a greater understanding of and improving care for veterans with SCI. C1 [Schilero, Gregory J.; Radulovic, Miroslav; Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.; Lesser, Marvin] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Schilero, Gregory J.; Radulovic, Miroslav; Wecht, Jill M.; Spungen, Ann M.; Bauman, William A.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Schilero, GJ (reprint author), James J Peters VA Med Ctr, Bronx, NY 10468 USA. EM greg.schilero@va.gov NR 63 TC 2 Z9 2 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2040 EI 1432-1750 J9 LUNG JI Lung PD JUN PY 2014 VL 192 IS 3 BP 339 EP 346 DI 10.1007/s00408-014-9575-8 PG 8 WC Respiratory System SC Respiratory System GA AH3LU UT WOS:000336025900001 PM 24723067 ER PT J AU Smith, DF Maleki, Z Coughlan, D Gooi, Z Akpeng, B Ogawa, T Bishop, JA Frick, KD Agrawal, N Gourin, CG Ha, PK Koch, WM Richmon, JD Westra, WH Pai, SI AF Smith, David F. Maleki, Zahra Coughlan, Diarmuid Gooi, Zhen Akpeng, Belinda Ogawa, Takenori Bishop, Justin A. Frick, Kevin D. Agrawal, Nishant Gourin, Christine G. Ha, Patrick K. Koch, Wayne M. Richmon, Jeremy D. Westra, William H. Pai, Sara I. TI Human papillomavirus status of head and neck cancer as determined in cytologic specimens using the hybrid-capture 2 assay SO ORAL ONCOLOGY LA English DT Article DE HPV; Head and neck cancer; Squamous cell carcinoma; Hybrid capture 2; Fine needle aspiration; Cytology ID SQUAMOUS-CELL CARCINOMA; OROPHARYNGEAL CANCER; TUMOR-ORIGIN; ORAL-CANCER; RISK; ASSOCIATION; SURVIVAL AB Objective: A standardized assay to determine the HPV status of head and neck squamous cell carcinoma (HNSCC) specimens has not yet been established, particularly for cytologic samples. The goal of this study was to determine whether the hybrid capture-2 (HC-2) assay, already widely used for the detection of high risk HPV in cervical brushings, is applicable to cytologic specimens obtained from patients with suspected HNSCCs. Materials and methods: Fine needle aspirates (FNA) of cervical lymph nodes were pre-operatively obtained from patients with suspected HNSCCs and evaluated for the presence of HPV using the HC-2 assay. HPV analysis was performed on the corresponding resected tissue specimens using p16 immunohistochemistry (IHC) and HR-HPV in situ hybridization (ISH). A cost analysis was performed using the Center for Medicare & Medicaid Services. Results: HPV status of the cervical lymph node metastases was correctly classified using the HC-2 assay in 84% (21/25) of cases. Accuracy was improved to 100% when cytologic evaluation confirmed the presence of cancer cells in the test samples. The estimated cost savings to CMS using the HC-2 assay ranged from $113.74 to $364.63 per patient. Conclusions: HC-2 is a reliable method for determining the HPV status of HNSCCs. Its application to HNSCCs may reduce costs by helping to localize the primary site during the diagnostic work-up as well as decrease the interval time of determining the HPV status which would be relevant for providing prognostic information to the patient as well as determining eligibility for clinical trials targeting this unique patient population. (c) 2014 Elsevier Ltd. All rights reserved. C1 [Smith, David F.; Gooi, Zhen; Akpeng, Belinda; Ogawa, Takenori; Agrawal, Nishant; Gourin, Christine G.; Ha, Patrick K.; Koch, Wayne M.; Richmon, Jeremy D.; Westra, William H.; Pai, Sara I.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. [Maleki, Zahra; Bishop, Justin A.; Westra, William H.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21287 USA. [Coughlan, Diarmuid; Frick, Kevin D.] Natl Univ Ireland, Dept Econ, Galway, Ireland. [Ogawa, Takenori] Tohoku Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Sendai, Miyagi 980, Japan. [Frick, Kevin D.] Johns Hopkins Carey Business Sch, Baltimore, MD 21202 USA. [Ha, Patrick K.] Greater Baltimore Med Ctr, Milton J Dance Jr Head & Neck Ctr, Baltimore, MD 21204 USA. [Westra, William H.; Pai, Sara I.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21287 USA. RP Pai, SI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, One Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM sipai@mgh.harvard.edu OI Maleki, Zahra/0000-0003-3273-4802 FU NIH/NCI [1R21CA176332-01] FX This work was funded by the NIH/NCI Grant 1R21CA176332-01 (SIP). NR 19 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD JUN PY 2014 VL 50 IS 6 BP 600 EP 604 DI 10.1016/j.oraloncology.2014.02.011 PG 5 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA AH1NY UT WOS:000335889000012 PM 24630260 ER PT J AU Mardirossian, V Karmali, F Merfeld, D AF Mardirossian, Vartan Karmali, Faisal Merfeld, Daniel TI Thresholds for Human Perception of Roll Tilt Motion: Patterns of Variability Based on Visual, Vestibular, and Mixed Cues SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Roll tilt; Sinusoidal acceleration motion; Vestibular; Vestibular thresholds; Visual; Visual-vestibular conditions; Visual-vestibular integration ID QUALITATIVELY DIFFERENT MECHANISMS; VERTICAL AXIS; TRANSLATION; RESPONSES; FREQUENCY; VOR AB Hypothesis: Visual and vestibular cues provide complementary information about spatial orientation. Background: A previous study we performed showed that visual and vestibular cues are fused when the brain judges the roll-tilt direction. However, it was unclear if the motion perception threshold measured in visual-vestibular conditions will be better than visual or vestibular thresholds at high frequencies. Methods: An innovative method of vestibular evaluation, the measurement of vestibular thresholds, was used. We used a Moog mobile platform with dedicated software. Four subjects were tested at 1, 2, 3, 4, and 5 Hz with adaptively decreasing amplitude. Subjects were asked to indicate the direction of motion in three conditions: vestibular only, subjects roll tilted in the dark; visual only, a visual scene was tilted in front of the subjects; and combined visual + vestibular, subjects rotated while watching a stationary visual scene. For each subject, we calculated the percentage difference between the threshold for combined visual/vestibular stimuli and the best of either the vestibular or visual threshold. Results: Visual and vestibular thresholds significantly differed in function of frequency. Conclusion: Vestibular and visual thresholds at different frequencies are significantly different, which support the fact that they use different perception pathways. The brain may determine the body motion in space during roll tilt motion by integration of vestibular and visual inputs: the combined estimate of motion is better than the vestibular input and is not significantly better than the visual cues alone. This research may be useful in the workup of vertiginous disorders with impaired integration of vestibular and visual cues (motion sickness and migraine dizziness). C1 [Mardirossian, Vartan] Boston Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA 02218 USA. [Karmali, Faisal; Merfeld, Daniel] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. RP Mardirossian, V (reprint author), Boston Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, 1 BMC Pl,FGH Bldg,4th Floor, Boston, MA 02218 USA. EM vartan74@gmail.com FU National Institutes of Health/National Institute on Deafness and Other Communication Disorders [DC04158, IRB MEEI 98-09-027] FX This study was supported by grant DC04158 from the National Institutes of Health/National Institute on Deafness and Other Communication Disorders (IRB MEEI 98-09-027). NR 6 TC 2 Z9 2 U1 1 U2 7 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 JUN PY 2014 VL 35 IS 5 BP 857 EP 860 PG 4 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AH6CQ UT WOS:000336218700024 PM 24691502 ER PT J AU Lepage, JF Clouchoux, C Lassonde, M Evans, AC Deal, CL Theoret, H AF Lepage, Jean-Francois Clouchoux, Cedric Lassonde, Maryse Evans, Alan C. Deal, Cheri L. Theoret, Hugo TI Cortical thickness correlates of socioemotional difficulties in adults with Turner syndrome SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Emotional Quotient Inventory; Social cognition; Turner syndrome; X-monosomy; Sex-chromosome aneuploidy ID EMOTIONAL INTELLIGENCE; X MONOSOMY; RECOGNITION; AMYGDALA; CORTEX; BRAIN AB Turner syndrome (TS) is a non-inherited genetic disorder associated with a specific cognitive phenotype and socioemotional impairments. The present study aimed at characterizing the neuroanatomical basis of socioemotional dysfunctions in TS using the Emotional Quotient inventory (EQ-I) and cortical morphology analysis in 17 individuals with TS (45,X) and 17-age and verbal IQ matched healthy females. Individuals with TS reported significantly greater socioemotional impairment than controls. Cortical thickness analysis showed that participants with TS had an overall thicker cortex than controls, with extensive alterations in the temporal, frontal, parietal and insular regions bilaterally. Using the total EQ-I score as regressor in the cortical thickness analysis revealed a number of brain regions where the relationship between cortical thickness and EQ-I score differed between groups; these areas included brain regions critically involved in socioemotional processes, such as bilateral insula, the anterior cingulate and the orbitofrontal cortex. These results show that socioemotional dysfunctions seen in women with TS are associated with significant alterations in brain morphology. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Lepage, Jean-Francois; Lassonde, Maryse; Theoret, Hugo] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. [Clouchoux, Cedric; Evans, Alan C.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Lassonde, Maryse; Deal, Cheri L.; Theoret, Hugo] Univ St Justine, Ctr Rech Ctr Hosp, Montreal, PQ, Canada. RP Lepage, JF (reprint author), Massachusetts Gen Hosp, Spaulding Rehabil Hosp, 79-96 13th St, Charlestown, MA 02129 USA. EM jf.lepage@gmail.com FU Canadian Institutes of Health Research (CIHR) [MOP-74608]; postdoctoral fellowship from the CIHR FX This work was supported by grants from the Canadian Institutes of Health Research (CIHR) (MOP-74608). JFL is supported by a postdoctoral fellowship from the CIHR. NR 18 TC 2 Z9 2 U1 3 U2 6 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 JUN PY 2014 VL 44 BP 30 EP 34 DI 10.1016/j.psyneun.2014.02.017 PG 5 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA AH3IN UT WOS:000336017000004 PM 24767617 ER PT J AU Kirchhoff, AC Montenegro, RE Warner, EL Wright, J Fluchel, M Stroup, AM Park, ER Kinney, AY AF Kirchhoff, Anne C. Montenegro, Roberto E. Warner, Echo L. Wright, Jennifer Fluchel, Mark Stroup, Antoinette M. Park, Elyse R. Kinney, Anita Y. TI Childhood cancer survivors' primary care and follow-up experiences SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Childhood cancer survivors; Primary care; Risk-based care; Survivor care plans ID YOUNG-ADULT SURVIVORS; HEALTH-CARE; PHYSICIANS; KNOWLEDGE; PERSPECTIVES; PROVIDERS; VIEWS AB Although most childhood cancer survivors see a primary care provider (PCP), little is known about these encounters. We explored themes related to survivors' (1) experiences with primary care, (2) communication with their PCPs about their cancer, and (3) their knowledge and impressions about follow-up care, including their interest in a survivor care plan (SCP). From April to July 2012, we conducted in-depth, semi-structured telephone interviews with 53 adult survivors recruited from the Utah Cancer Surveillance, Epidemiology, and End Results (SEER) Registry. Participants were randomly selected from sex, age, and rural/urban strata and were younger than 21 years at the time of diagnosis. Participants were asked if they had a PCP and whether they discussed their cancer history with their provider and their interest in a SCP. Interviews were recorded, transcribed, and content-analyzed. The average age at interview was 39.1 years (SD = 11.2). Most survivors had a current PCP (83.0 %). Almost half were not worried about their health despite having had cancer. Detailed discussions about cancer history with PCPs were generally rare. Few survivors had a follow-up care plan, but over half thought a SCP could empower their medical decision making. However, one-third of the survivors were skeptical about the usefulness of a SCP and some were worried about health-care costs. Childhood cancer survivors need better care coordination. Of concern is that many do not discuss their cancer history with their current PCPs and most have no SCP. C1 [Kirchhoff, Anne C.; Warner, Echo L.; Fluchel, Mark] Huntsman Canc Inst, Canc Control & Populat Sci Res Program, Salt Lake City, UT 84112 USA. [Kirchhoff, Anne C.; Wright, Jennifer; Fluchel, Mark] Univ Utah, Dept Pediat, Salt Lake City, UT USA. [Kirchhoff, Anne C.; Wright, Jennifer; Fluchel, Mark] Huntsman Canc Inst, Ctr Childrens Canc Res, Salt Lake City, UT 84112 USA. [Montenegro, Roberto E.] Yale Univ, Dept Psychiat, New Haven, CT 06511 USA. [Stroup, Antoinette M.] Rutgers State Univ, Sch Publ Hlth, Trenton, NJ USA. [Stroup, Antoinette M.] Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Park, Elyse R.] Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Park, Elyse R.] Dept Psychiat, Boston, MA 02114 USA. [Park, Elyse R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kinney, Anita Y.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA. [Kinney, Anita Y.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. RP Kirchhoff, AC (reprint author), Huntsman Canc Inst, Ctr Childrens Canc Res, Salt Lake City, UT 84112 USA. EM anne.kirchhoff@hci.utah.edu FU Huntsman Cancer Institute's Cancer Control and Population Sciences Pilot Grant Program; Primary Children's Medical Foundation; National Cancer Institute [HHSN261201000026C]; Utah State Department of Health; University of Utah FX Support for this research comes from the Huntsman Cancer Institute's Cancer Control and Population Sciences Pilot Grant Program and the Cancer Center Support Grant and Primary Children's Medical Foundation Career Development Award. We also acknowledge the use of shared resources supported by P30 CA042014 awarded to Huntsman Cancer Institute. Additional support for the Utah Cancer Registry provided by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Contract # HHSN261201000026C, the Utah State Department of Health, and the University of Utah. NR 27 TC 6 Z9 6 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 EI 1433-7339 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD JUN PY 2014 VL 22 IS 6 BP 1629 EP 1635 DI 10.1007/s00520-014-2130-6 PG 7 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA AG9YC UT WOS:000335775000023 PM 24496759 ER PT J AU Lee, V Singh, G Trasatti, JP Bjornsson, C Xu, XW Tran, TN Yoo, SS Dai, GH Karande, P AF Lee, Vivian Singh, Gurtej Trasatti, John P. Bjornsson, Chris Xu, Xiawei Thanh Nga Tran Yoo, Seung-Schik Dai, Guohao Karande, Pankaj TI Design and Fabrication of Human Skin by Three-Dimensional Bioprinting SO TISSUE ENGINEERING PART C-METHODS LA English DT Article ID RECONSTRUCTED HUMAN EPIDERMIS; TISSUE-ENGINEERING SCAFFOLDS; TRANSCUTANEOUS IMMUNIZATION; PENETRATION ENHANCERS; FREEFORM FABRICATION; LANGERHANS CELLS; IN-VITRO; KERATINOCYTES; CULTURE; MODELS AB Three-dimensional (3D) bioprinting, a flexible automated on-demand platform for the free-form fabrication of complex living architectures, is a novel approach for the design and engineering of human organs and tissues. Here, we demonstrate the potential of 3D bioprinting for tissue engineering using human skin as a prototypical example. Keratinocytes and fibroblasts were used as constituent cells to represent the epidermis and dermis, and collagen was used to represent the dermal matrix of the skin. Preliminary studies were conducted to optimize printing parameters for maximum cell viability as well as for the optimization of cell densities in the epidermis and dermis to mimic physiologically relevant attributes of human skin. Printed 3D constructs were cultured in submerged media conditions followed by exposure of the epidermal layer to the air-liquid interface to promote maturation and stratification. Histology and immunofluorescence characterization demonstrated that 3D printed skin tissue was morphologically and biologically representative of in vivo human skin tissue. In comparison with traditional methods for skin engineering, 3D bioprinting offers several advantages in terms of shape- and form retention, flexibility, reproducibility, and high culture throughput. It has a broad range of applications in transdermal and topical formulation discovery, dermal toxicity studies, and in designing autologous grafts for wound healing. The proof-of-concept studies presented here can be further extended for enhancing the complexity of the skin model via the incorporation of secondary and adnexal structures or the inclusion of diseased cells to serve as a model for studying the pathophysiology of skin diseases. C1 [Lee, Vivian; Dai, Guohao] Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY 12180 USA. [Lee, Vivian; Singh, Gurtej; Trasatti, John P.; Dai, Guohao; Karande, Pankaj] Rensselaer Polytech Inst, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA. [Singh, Gurtej; Karande, Pankaj] Rensselaer Polytech Inst, Howard P Isermann Dept Chem & Biol Engn, Troy, NY 12180 USA. [Trasatti, John P.] Rensselaer Polytech Inst, Dept Chem & Chem Biol, Troy, NY 12180 USA. [Bjornsson, Chris] Neural Stem Cell Inst, Rensselaer, NY USA. [Xu, Xiawei] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thanh Nga Tran] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Yoo, Seung-Schik] Harvard Univ, Sch Med, Boston, MA USA. RP Dai, GH (reprint author), Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY 12180 USA. EM daig@rpi.edu OI Dai, Guohao/0000-0001-7346-2685 NR 50 TC 47 Z9 54 U1 14 U2 203 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 JUN 1 PY 2014 VL 20 IS 6 BP 473 EP 484 DI 10.1089/ten.tec.2013.0335 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA AH2YE UT WOS:000335987200003 PM 24188635 ER PT J AU Winslow, V Vaivoda, R Vasilyev, A Dombkowski, D Douaidy, K Stark, C Drake, J Guilliams, E Choudhary, D Preffer, F Stoilov, I Christmas, P AF Winslow, Valeria Vaivoda, Rachel Vasilyev, Aleksandr Dombkowski, David Douaidy, Karim Stark, Christopher Drake, Justin Guilliams, Evin Choudhary, Dharamainder Preffer, Frederic Stoilov, Ivaylo Christmas, Peter TI Altered leukotriene B-4 metabolism in CYP4F18-deficient mice does not impact inflammation following renal ischemia SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE Cytochrome P450; Neutrophil; Leukotriene B4; omega-Hydroxylase; Inflammation ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; INNATE IMMUNE-SYSTEM; HUMAN LIVER-CELLS; REPERFUSION INJURY; DENDRITIC CELLS; TARGETED DISRUPTION; DIHYDRO METABOLITES; CYP4F SUBFAMILY; DEFICIENT MICE; KIDNEY INJURY AB Inflammatory responses to infection and injury must be restrained and negatively regulated to minimize damage to host tissue. One proposed mechanism involves enzymatic inactivation of the pro-inflammatory mediator leukotriene B-4, but it is difficult to dissect the roles of various metabolic enzymes and pathways. A primary candidate for a regulatory pathway is omega oxidation of leukotriene B-4 in neutrophils, presumptively by CYP4F3A in humans and CYP4F18 in mice. This pathway generates omega, omega-1, and omega-2 hydroxylated products of leukotriene B4, depending on species. We created mouse models targeting exons 8 and 9 of the Cyp4f18 allele that allows both conventional and conditional knockouts of Cyp4f18. Neutrophils from wild-type mice convert leukotriene B-4 to 19-hydroxy leukotriene B-4, and to a lesser extent 18-hydroxy leukotriene B-4, whereas these products were not detected in neutrophils from conventional Cyp4f18 knockouts. A mouse model of renal ischemia-reperfusion injury was used to investigate the consequences of loss of CYP4F18 in vivo. There were no significant changes in infiltration of neutrophils and other leukocytes into kidney tissue as determined by flow cytometry and immunohistochemistry, or renal injury as assessed by histological scoring and measurement of blood urea nitrogen. It is concluded that CYP4F18 is necessary for omega oxidation of leukotriene B-4 in neutrophils, and is not compensated by other CYP enzymes, but loss of this metabolic pathway is not sufficient to impact inflammation and injury following renal ischemia-reperfusion in mice. (C) 2014 Elsevier B.V. All rights reserved. C1 [Winslow, Valeria; Vaivoda, Rachel; Vasilyev, Aleksandr; Douaidy, Karim; Stark, Christopher; Christmas, Peter] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Charlestown, MA 02129 USA. [Dombkowski, David; Preffer, Frederic] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Drake, Justin; Guilliams, Evin; Christmas, Peter] Radford Univ, Dept Biol, Radford, VA 24142 USA. [Choudhary, Dharamainder; Stoilov, Ivaylo] Univ Connecticut, Ctr Hlth, Dept Surg, Farmington, CT 06030 USA. RP Christmas, P (reprint author), Radford Univ, Dept Biol, Radford, VA 24142 USA. EM pchristma2@radford.edu FU National Institutes of Health Grant [R0IDK074821]; National Center for Research Resources, National Institutes of Health Grant [S10RR027926] FX This project was supported by the National Institutes of Health Grant R0IDK074821 (to P. Christmas). LC-MS/MS analysis was performed at the Wayne State University Lipidomics Core Facility and was supported in part by the National Center for Research Resources, National Institutes of Health Grant S10RR027926; we thank Dr. Krishnarao Maddipati for help with the analysis. NR 53 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 EI 0006-3002 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD JUN PY 2014 VL 1841 IS 6 BP 868 EP 879 DI 10.1016/j.bbalip.2014.03.002 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AG7SI UT WOS:000335618300005 PM 24632148 ER PT J AU Partridge, AH Pagani, O Abulkhair, O Aebi, S Amant, F Azim, HA Costa, A Delaloge, S Freilich, G Gentilini, OD Harbeck, N Kelly, CM Loibl, S Meirow, D Peccatori, F Kaufmann, B Cardoso, F AF Partridge, Ann H. Pagani, Olivia Abulkhair, Omalkhair Aebi, Stefan Amant, Frederic Azim, Hatem A., Jr. Costa, Alberto Delaloge, Suzette Freilich, Gloria Gentilini, Oreste Davide Harbeck, Nadia Kelly, Catherine M. Loibl, Sibylle Meirow, Dror Peccatori, Fedro Kaufmann, Bella Cardoso, Fatima TI First international consensus guidelines for breast cancer in young women (BCY1) SO BREAST LA English DT Article DE Breast cancer; Guidelines; BCY1 ID BRCA2 MUTATION CARRIERS; ADJUVANT ENDOCRINE THERAPY; GOSERELIN PLUS ANASTROZOLE; NIPPLE-SPARING MASTECTOMY; POPULATION-BASED COHORT; BONE-MINERAL DENSITY; PREMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; CONSERVING TREATMENT; FOLLOW-UP AB The 1st International Consensus Conference for Breast Cancer in Young Women (BCY1) took place in November 2012, in Dublin, Ireland organized by the European School of Oncology (ESO). Consensus recommendations for management of breast cancer in young women were developed and areas of research priorities were identified. This manuscript summarizes these international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA). (C) 2014 Elsevier Ltd. All rights reserved. C1 [Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Pagani, Olivia] Oncol Inst Southern Switzerland, Bellinzona, Switzerland. [Pagani, Olivia] Breast Unit Southern Switzerland, Bellinzona, Switzerland. [Abulkhair, Omalkhair] King Abdulaziz Med City Natl Guard, Riyadh, Saudi Arabia. [Aebi, Stefan] Luzerner Kantonsspital, Luzern, Switzerland. [Amant, Frederic] Univ Hosp Leuven, Louvain, Belgium. [Azim, Hatem A., Jr.] Univ Libre Bruxelles, Inst Jules Bordet, BrEAST Data Ctr, Dept Med, Brussels, Belgium. [Costa, Alberto; Peccatori, Fedro] European Sch Oncol, Milan, Italy. [Delaloge, Suzette] Inst Gustave Roussy, Villejuif, France. [Freilich, Gloria] Europa Donna, London, England. [Gentilini, Oreste Davide; Peccatori, Fedro; Cardoso, Fatima] European Inst Oncol, Milan, Italy. [Harbeck, Nadia] Univ Munich LMU, Dept OB&GYN, Breast Ctr, Munich, Germany. [Kelly, Catherine M.] Mater Misericordiae Univ Hosp, Dublin, Ireland. [Loibl, Sibylle] GBG Forschungs GmbH, German Breast Grp, Neu Isenburg, Germany. [Loibl, Sibylle] Sana Klinikum Offenbach, Offenbach, Germany. [Meirow, Dror] Sheba Med Ctr, Ramat Gan, Israel. [Kaufmann, Bella] Sheba Med Ctr, Tel Hashomer, Israel. [Cardoso, Fatima] Champalimaud Canc Ctr, Breast Unit, Lisbon, Portugal. RP Cardoso, F (reprint author), Champalimaud Canc Ctr, Breast Unit, Av Brasilia,S-N, P-1400038 Lisbon, Portugal. EM fatimacardoso@fundacaochampalimaud.pt RI Aebi, Stefan/F-2004-2010; OI Aebi, Stefan/0000-0002-3383-9449; Cardoso, Fatima/0000-0002-6692-2249 NR 129 TC 40 Z9 40 U1 1 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD JUN PY 2014 VL 23 IS 3 BP 209 EP 220 DI 10.1016/j.breast.2014.03.011 PG 12 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA AG6DV UT WOS:000335509600003 PM 24767882 ER PT J AU Roper, J Sinnamon, MJ Coffee, EM Belmont, P Keung, L Georgeon-Richard, L Wang, WV Faber, AC Yun, J Yilmaz, OH Bronson, RT Martin, ES Tsichlis, PN Hung, KE AF Roper, Jatin Sinnamon, Mark J. Coffee, Erin M. Belmont, Peter Keung, Lily Georgeon-Richard, Larissa Wang, Wei Vivian Faber, Anthony C. Yun, Jihye Yilmaz, Oemer H. Bronson, Roderick T. Martin, Eric S. Tsichlis, Philip N. Hung, Kenneth E. TI Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer SO CANCER LETTERS LA English DT Article DE PI3K; MEK; KRAS; Colorectal cancer; Mouse model of cancer ID SYNTHETIC LETHAL INTERACTION; COLON-CANCER; LUNG ADENOCARCINOMA; MEK INHIBITORS; BRAF MUTATIONS; MOUSE MODEL; RAS; PATHWAY; GROWTH; CARCINOMAS AB PI3K inhibition in combination with other agents has not been studied in the context of P1K3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced tumor regression in a mouse model of P1K3CA wild-type, KRAS mutant colorectal cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and activation of BIM. These findings implicate mitochondrial-dependent apoptotic mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the treatment of PIK3CA wild-type, KRAS mutant cancer. (C) 2014 Elsevier Ireland Ltd. All rights reserved. C1 [Roper, Jatin; Georgeon-Richard, Larissa; Wang, Wei Vivian] Tufts Med Ctr, Div Gastroenterol, Dept Med, Boston, MA 02111 USA. [Sinnamon, Mark J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Coffee, Erin M.; Faber, Anthony C.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Belmont, Peter] Celgene, Discovery, Oncol Res, San Diego, CA USA. [Roper, Jatin; Keung, Lily; Tsichlis, Philip N.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA USA. [Yun, Jihye] Weill Cornell Med Coll, New York, NY USA. [Yun, Jihye] New York Presbyterian Hosp, Dept Med, New York, NY USA. [Yilmaz, Oemer H.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Bronson, Roderick T.; Martin, Eric S.] Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA USA. [Hung, Kenneth E.] Pfizer Biotherapeut Clin Res, Cambridge, MA USA. RP Roper, J (reprint author), Tufts Med Ctr, Div Gastroenterol, Dept Med, Boston, MA 02111 USA. EM jroper@tuftsmedicalcenter.org FU American Gastroenterological Association FX American Gastroenterological Association (Fellowship to Faculty Transition Award to J.R.). NR 50 TC 18 Z9 19 U1 1 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD JUN 1 PY 2014 VL 347 IS 2 BP 204 EP 211 DI 10.1016/j.canlet.2014.02.018 PG 8 WC Oncology SC Oncology GA AG7WJ UT WOS:000335629200007 PM 24576621 ER PT J AU Marien, P Ackermann, H Adamaszek, M Barwood, CHS Beaton, A Desmond, J De Witte, E Fawcett, AJ Hertrich, I Kuper, M Leggio, M Marvel, C Molinari, M Murdoch, BE Nicolson, RI Schmahmann, JD Stoodley, CJ Thurling, M Timmann, D Wouters, E Ziegler, W AF Marien, Peter Ackermann, Herman Adamaszek, Michael Barwood, Caroline H. S. Beaton, Alan Desmond, John De Witte, Elke Fawcett, Angela J. Hertrich, Ingo Kueper, Michael Leggio, Maria Marvel, Cherie Molinari, Marco Murdoch, Bruce E. Nicolson, Roderick I. Schmahmann, Jeremy D. Stoodley, Catherine J. Thuerling, Markus Timmann, Dagmar Wouters, Ellen Ziegler, Wolfram TI Consensus Paper: Language and the Cerebellum: an Ongoing Enigma SO CEREBELLUM LA English DT Article DE Cerebellum; Language; Speech; Speech perception; Apraxia of speech; Working memory; Verbal fluency; Syntax; Phonology; Semantics; Aphasia; Imaging; Agraphia; Dyslexia; Functional topography; Imaging; fMRI; SPECT ID VERBAL WORKING-MEMORY; COGNITIVE-AFFECTIVE SYNDROME; POSITRON-EMISSION-TOMOGRAPHY; FOREIGN ACCENT SYNDROME; FOSSA TUMOR RESECTION; SPEECH PRODUCTION; BRAIN ACTIVATION; FUNCTIONAL MRI; BASAL GANGLIA; TEMPORAL-LOBE AB In less than three decades, the concept "cerebellar neurocognition" has evolved from a mere afterthought to an entirely new and multifaceted area of neuroscientific research. A close interplay between three main strands of contemporary neuroscience induced a substantial modification of the traditional view of the cerebellum as a mere coordinator of autonomic and somatic motor functions. Indeed, the wealth of current evidence derived from detailed neuroanatomical investigations, functional neuroimaging studies with healthy subjects and patients and in-depth neuropsychological assessment of patients with cerebellar disorders shows that the cerebellum has a cardinal role to play in affective regulation, cognitive processing, and linguistic function. Although considerable progress has been made in models of cerebellar function, controversy remains regarding the exact role of the "linguistic cerebellum" in a broad variety of nonmotor language processes. This consensus paper brings together a range of different viewpoints and opinions regarding the contribution of the cerebellum to language function. Recent developments and insights in the nonmotor modulatory role of the cerebellum in language and some related disorders will be discussed. The role of the cerebellum in speech and language perception, in motor speech planning including apraxia of speech, in verbal working memory, in phonological and semantic verbal fluency, in syntax processing, in the dynamics of language production, in reading and in writing will be addressed. In addition, the functional topography of the linguistic cerebellum and the contribution of the deep nuclei to linguistic function will be briefly discussed. As such, a framework for debate and discussion will be offered in this consensus paper. C1 [Marien, Peter; De Witte, Elke; Wouters, Ellen] Vrije Univ Brussel, Dept Clin & Expt Neurolinguist, CLIN, Brussels, Belgium. [Marien, Peter; Wouters, Ellen] ZNA Middelheim Gen Hosp, Dept Neurol, B-2020 Antwerp, Belgium. [Marien, Peter] Royal Flemish Acad Belgium Sci & Arts, Vlaams Acad Centrum VLAC, Inst Adv Studies, Brussels, Belgium. [Ackermann, Herman; Hertrich, Ingo] Univ Tubingen, Dept Gen Neurol, Ctr Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany. [Adamaszek, Michael] Univ Leipzig, Ctr Neurol Rehabil, Bennewitz, Germany. [Barwood, Caroline H. S.; Murdoch, Bruce E.] Univ Queensland, Ctr Neurogen Commun Disorders Res, Sch Hlth & Rehabil Sci, Brisbane, Qld, Australia. [Beaton, Alan] Swansea Univ, Dept Psychol, Aberystwyth, Dyfed, Wales. [Beaton, Alan] Dept Psychol, Aberystwyth, Dyfed, Wales. [Desmond, John; Marvel, Cherie] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Fawcett, Angela J.] Univ Swansea, Ctr Child Res, Swansea, W Glam, Wales. [Kueper, Michael; Thuerling, Markus; Timmann, Dagmar] Univ Duisburg Essen, Dept Neurol, Essen, Germany. [Leggio, Maria] Univ Roma La Sapienza, Dept Psychol, I-00185 Rome, Italy. [Leggio, Maria; Molinari, Marco] IRCCS Santa Lucia Fdn, Rome, Italy. [Nicolson, Roderick I.] Univ Sheffield, Dept Psychol, Sheffield S10 2TN, S Yorkshire, England. [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Ataxia Unit, Cognit & Behav Neurol Unit, Lab Neuroanat & Cerebellar Neurobiol,Dept Neurol, Boston, MA 02114 USA. [Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA USA. [Stoodley, Catherine J.] Amer Univ, Dept Psychol, Washington, DC 20016 USA. [Ziegler, Wolfram] City Hosp, Clin Neuropsychol Res Grp, Clin Neuropsychol, Munich, Germany. [Ziegler, Wolfram] Univ Munich, Inst Phonet & Speech Proc, Munich, Germany. RP Marien, P (reprint author), ZNA Middelheim Gen Hosp, Dept Neurol, Lindendreef 1, B-2020 Antwerp, Belgium. EM peter.marien5@telenet.be RI Molinari, Marco/A-9624-2010; Stoodley, Catherine/P-2081-2016; OI Molinari, Marco/0000-0001-9808-9688; Stoodley, Catherine/0000-0003-2629-0213; Leggio, Maria /0000-0003-3750-2760 FU NIH [K01 DA0304425, R01 AA018694]; DFG TI [239/9-1] FX This study is supported by NIH grants K01 DA0304425 (Dr. Marvel) and R01 AA018694 (Dr. Desmond) and by DFG TI 239/9-1. The editorial assistance of Mrs. Tine D'aes is greatly acknowledged. NR 267 TC 51 Z9 52 U1 12 U2 66 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1473-4222 EI 1473-4230 J9 CEREBELLUM JI Cerebellum PD JUN PY 2014 VL 13 IS 3 BP 386 EP 410 DI 10.1007/s12311-013-0540-5 PG 25 WC Neurosciences SC Neurosciences & Neurology GA AG9LB UT WOS:000335739600011 PM 24318484 ER PT J AU Tang, HY Sayers, SL Weissinger, G Riegel, B AF Tang, Hsin-Yi (Jean) Sayers, Steven L. Weissinger, Guy Riegel, Barbara TI The Role of Depression in Medication Adherence Among Heart Failure Patients SO CLINICAL NURSING RESEARCH LA English DT Article DE heart failure; depression; major depressive disorders; medication adherence ID SELF-REPORT; NONADHERENCE; DISEASE; ANXIETY; RECOMMENDATIONS; NONCOMPLIANCE; INTERVENTION; METAANALYSIS; ASSOCIATION; PREVALENCE AB The purpose of the study was to explore the association between depression and medication adherence in heart failure (HF) patients. Studies have shown that people with depression are likely to be nonadherent to their prescribed medication treatment. But other studies suggest that nonadherence may be overestimated by people with depression. A total of 244 adults with Stage C HF completed the study. Self-reported medication adherence was obtained using the Basel Assessment of Adherence Scale (BAAS); objective data on medication adherence were collected using the electronic Medication Event Monitoring System (MEMS). Depression was measured via self-report with the Patient Health Questionnaire (PHQ-9). There was a significant difference between depressed and nondepressed participants in self-reported medication nonadherence (p = .008), but not in objectively measured medication nonadherence (p = .72). The depressed sample was 2.3 times more likely to self-report poor medication adherence than those who were nondepressed (p = .006). C1 [Tang, Hsin-Yi (Jean)] Seattle Univ, Coll Nursing, Seattle, WA 98125 USA. [Sayers, Steven L.] Vet Affairs Med Ctr, Philadelphia, PA USA. [Weissinger, Guy] Univ Penn, Perelman Sch Med, Aaron T Beck Ctr Psychopathol Res, Philadelphia, PA 19104 USA. [Riegel, Barbara] Univ Penn, Sch Nursing, Biobehav Res Ctr, Philadelphia, PA 19104 USA. RP Tang, HY (reprint author), Seattle Univ, Coll Nursing, 901 12th Ave POB 222000, Seattle, WA 98125 USA. EM jeantang@u.washington.edu FU National Heart, Lung & Blood Institute [RO1 HL084394-01A1]; Philadelphia Veterans Affairs Medical Center, VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC); Hope Heart Institute, Seattle, Washington FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was funded by (a) National Heart, Lung & Blood Institute (RO1 HL084394-01A1), (b) Philadelphia Veterans Affairs Medical Center, VISN 4 Mental Illness Research, Education, and Clinical Center (MIREC) [the opinions expressed herein do not represent the official policy of the Department of Veterans Affairs], and (c) Hope Heart Institute, Seattle, Washington. NR 40 TC 5 Z9 5 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1054-7738 EI 1552-3799 J9 CLIN NURS RES JI Clin. Nurs. Res. PD JUN PY 2014 VL 23 IS 3 BP 231 EP 244 DI 10.1177/1054773813481801 PG 14 WC Nursing SC Nursing GA AG7EF UT WOS:000335580200001 PM 23548500 ER PT J AU Gavigan, A Cain, C Carroll, DL AF Gavigan, Anne Cain, Carolyn Carroll, Diane L. TI Effects of Informational Sessions on Anxiety Precardiovascular Procedure SO CLINICAL NURSING RESEARCH LA English DT Article DE patient education; anxiety assessment; percutaneous coronary intervention; patient satisfaction ID ACUTE MYOCARDIAL-INFARCTION; CARDIAC PATIENTS; IMPACT; EDUCATION; HEALTH; LIFE AB To measure the effect of an informational video intervention (IVI) compared to standard care (SC) preparation on anxiety and satisfaction prior to percutaneous cardiovascular procedure (PCVP). A quasi-experimental, randomized, prepost design was used to measure the effect of IVI, provided pre-PCVP, compared with SC only preparation on admission anxiety compared with post the IVI and SC preparation. There were 113 males/72 females, mean age of 61.8 years, assigned to IVI (n = 94) or SC group (n = 91). After the preparatory information session, there was no difference between groups on state anxiety (37.6 +/- 11.7 vs. 36.3 +/- 10.7; z = -.500, p = .617). There was a significant improvement in satisfaction in IVI group (54.23 +/- 5.5 vs. 50.7 +/- 6.6 (z = -2.9, p = .003). IVI session improved satisfaction with preparation. Viewing the IVI within hours of a PCVP did not reduce measurable anxiety. Further research may reveal a more ideal viewing time. C1 [Gavigan, Anne; Cain, Carolyn; Carroll, Diane L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carroll, DL (reprint author), Massachusetts Gen Hosp, POB 426, Boston, MA 02114 USA. EM dcarroll3@partners.org FU Yvonne L. Munn Nursing Research Award, Patient Care Services, Massachusetts General Hospital, Boston MA FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Yvonne L. Munn Nursing Research Award, Patient Care Services, Massachusetts General Hospital, Boston MA. NR 28 TC 0 Z9 0 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1054-7738 EI 1552-3799 J9 CLIN NURS RES JI Clin. Nurs. Res. PD JUN PY 2014 VL 23 IS 3 BP 281 EP 295 DI 10.1177/1054773813483138 PG 15 WC Nursing SC Nursing GA AG7EF UT WOS:000335580200004 PM 23548501 ER PT J AU Greene, ME Rolfson, O Nemes, S Gordon, M Malchau, H Garellick, G AF Greene, Meridith E. Rolfson, Ola Nemes, Szilard Gordon, Max Malchau, Henrik Garellick, Goran TI Education Attainment is Associated With Patient-reported Outcomes: Findings From the Swedish Hip Arthroplasty Register SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID KNEE-JOINT REPLACEMENT; IMPORTANT DIFFERENCE; FUNCTIONAL STATUS; MODEL SELECTION; OSTEOARTHRITIS; OCCUPATION; SURGERY; HEALTH; INCOME; NEED AB Age, sex, and medical comorbidities may be associated with differences in patient-reported outcome scores after THA. Highest level of education may be a surrogate for socioeconomic status, but the degree to which this is associated with patient-reported outcomes after THA is not known. We investigated the national Swedish Hip Arthroplasty Register for the association of education attainment on patient-reported outcomes 1 year after THA; specifically, we evaluated level of education attainment against health-related quality of life (HRQoL), pain reduction, and satisfaction with treatment 1 year after THA. All THAs for osteoarthritis performed from 2005 through 2007 with complete patient-reported outcome measures (representing 49% of the THAs performed for this diagnosis) were selected from the Swedish Hip Arthroplasty Register. These cases were merged with national databases containing education attainment, marital status, and comorbidities (n = 11,464; mean age of patients, 64 years). The patient-reported outcome measure protocol included the HRQoL measure EuroQol five-dimension scale (EQ-5D), a VAS for pain, the Charnley classification survey, and a VAS addressing THA satisfaction. Linear regression analyses determined the association of preoperative patient factors with patient-reported outcomes. High education attainment was associated with higher HRQoL (EQ-5D index (high) = 0.03 +/- A 0.01; EQ VAS (high) = 2.6 +/- A 0.5) after THA, whereas those with low and medium education were at risk for lower HRQoL. High education was associated with less pain after treatment ((high) = -3.3 +/- A 0.05). Individuals with low or medium education were at risk for less satisfaction with THA (p < 0.001). Our results suggest clinicians should support patients with low and medium education to a greater extent. Identification of patients who will benefit most from THA and educating those at risk for poorer outcomes, like patients with low and medium education, ultimately may improve patient satisfaction, HRQoL, pain, and the cost utility of THA. C1 [Greene, Meridith E.; Rolfson, Ola; Nemes, Szilard; Gordon, Max; Malchau, Henrik; Garellick, Goran] Swedish Hip Arthroplasty Register, Gothenburg, Sweden. [Greene, Meridith E.; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Greene, Meridith E.; Rolfson, Ola; Malchau, Henrik; Garellick, Goran] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Orthopaed, Gothenburg, Sweden. [Gordon, Max] Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden. RP Greene, ME (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Lab, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. EM megreene@partners.org RI Gordon, Max/M-4330-2014; OI Gordon, Max/0000-0002-8080-5815; Nemes, Szilard/0000-0002-4145-1786; Rolfson, Ola/0000-0001-6534-1242 FU Swedish Hip Arthroplasty Register, Gothenburg, Sweden; Harris Orthopaedic Laboratory, Boston, MA, USA; Dr Felix Neuberghs Foundation, Gothenburg, Sweden FX This study was funded by the Swedish Hip Arthroplasty Register, Gothenburg, Sweden (GG), the Harris Orthopaedic Laboratory, Boston, MA, USA (HM), and research grants from Dr Felix Neuberghs Foundation, Gothenburg, Sweden (OR). NR 27 TC 20 Z9 20 U1 1 U2 2 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 JUN PY 2014 VL 472 IS 6 BP 1868 EP 1876 DI 10.1007/s11999-014-3504-2 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AG8KY UT WOS:000335668500029 PM 24549772 ER PT J AU Flinterman, HJA Doornberg, JN Guitton, TG Ring, D Goslings, JC Kloen, P AF Flinterman, Hendrik J. A. Doornberg, Job N. Guitton, Thierry G. Ring, David Goslings, J. Carel Kloen, Peter TI Long-term Outcome of Displaced, Transverse, Noncomminuted Olecranon Fractures SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SURGICAL-TREATMENT; ELBOW FUNCTION; PROXIMAL ULNA; HEALTH-STATUS; TENSION; FIXATION; STABILITY; WIRES; HEAD AB Operative treatment of a displaced, transverse, noncomminuted fracture of the olecranon is associated with good to excellent elbow function in retrospective short-term followup studies. However, to our knowledge, no studies have evaluated objective and subjective outcomes using standardized outcome instruments (ie, DASH and Mayo Elbow Performance Index [MEPI]) to quantify long-term outcome of these specific fractures. We evaluated (1) factors associated with disability, as measured with the DASH questionnaire; (2) factors associated with ulnohumeral motion; (3) factors associated with pain intensity; and (4) general descriptive findings for posttraumatic arthrosis, MEPI, ulnar neuropathy symptoms, and return to work between 10 and 32 years after open reduction and internal fixation (ORIF) of a transverse, noncomminuted fracture of the olecranon. Between 1977 and 1997, we performed ORIFs of transverse, noncomminuted olecranon fractures in 109 patients, of whom 35 had died, 14 had incomplete data in our registry, and 19 were lost to followup or declined participation, leaving 41 patients available for followup at a minimum of 10 years after surgery. During that time, our general indication for performing ORIF was greater than 2 mm displacement. The average age of these patients at the time of injury was 35 years (range, 18-73 years). Patient-reported outcome was quantified using the DASH questionnaire, and physician-based outcome was evaluated using the MEPI. To identify factors associated with disability (DASH), impairment (MEPI), ulnohumeral motion, and pain, we examined demographic and clinical data in bivariate analyses, and subsequently significant factors in multivariate analysis to identify independent predictors of outcome. The sole factor associated with higher DASH scores in multivariable analysis was age at surgery, explaining 20% of the variability, with younger patients performing better. The mean arc of elbow flexion was 142A degrees (range, 110A degrees-160A degrees), and the variation was associated with arthrosis alone (ie, a greater arc of motion was associated with a lesser grade of arthrosis according to the system of Broberg and Morrey). Pain was uncommon and generally was correlated with adverse events. The good results of operative fixation (tension-band wiring) of a transverse, displaced olecranon fracture are durable with time. Patient-reported outcomes are excellent in the majority of patients. Residual patient-rated disability does not correlate with arthrosis or loss of extension. C1 [Flinterman, Hendrik J. A.; Doornberg, Job N.] Orthotrauma Res Ctr Amsterdam, Amsterdam, Netherlands. [Doornberg, Job N.; Guitton, Thierry G.] Univ Amsterdam, Orthopaed Residency Program, Amsterdam, Netherlands. [Ring, David] Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Med Sch,Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. [Goslings, J. Carel] Acad Med Ctr Amsterdam, Dept Surg, Trauma Unit, NL-1100 DD Amsterdam, Netherlands. [Doornberg, Job N.; Kloen, Peter] Acad Med Ctr Amsterdam, Dept Orthopaed Surg, NL-1100 DD Amsterdam, Netherlands. RP Doornberg, JN (reprint author), Acad Med Ctr Amsterdam, Dept Orthopaed Surg, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands. EM jdoornberg@partners.org OI Guitton, Thierry/0000-0002-2599-1985 FU Keuning-Marti-Eckhardt Foundation, Amsterdam, The Netherlands FX One of the authors (JND) received funding from the Keuning-Marti-Eckhardt Foundation, Amsterdam, The Netherlands. NR 30 TC 4 Z9 6 U1 0 U2 1 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 JUN PY 2014 VL 472 IS 6 BP 1955 EP 1961 DI 10.1007/s11999-014-3481-5 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA AG8KY UT WOS:000335668500040 PM 24522384 ER PT J AU Rana, HQ Rainville, IR Vaidya, A AF Rana, Huma Q. Rainville, Irene R. Vaidya, Anand TI Genetic testing in the clinical care of patients with pheochromocytoma and paraganglioma SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE counselling; genetic testing; inheritance; next-generation sequencing; paraganglioma; pheochromocytoma ID ENDOCRINE NEOPLASIA TYPE-2; MITOCHONDRIAL COMPLEX II; HIPPEL-LINDAU-DISEASE; GASTROINTESTINAL STROMAL TUMORS; GENOTYPE-PHENOTYPE CORRELATIONS; MEDULLARY-THYROID CANCER; COWDEN-LIKE SYNDROME; SUCCINATE-DEHYDROGENASE; GERMLINE MUTATIONS; NEUROFIBROMATOSIS TYPE-1 AB Purpose of reviewParaganglioma and pheochromocytoma (PGL/PCC) are tumours of neural crest origin that can present along a clinical spectrum ranging from apparently sporadic, isolated tumours to a more complex phenotype of one or multiple tumours in the context of other clinical features and family history suggestive of a defined hereditary syndrome. Genetic testing for hereditary PGL/PCC can help to confirm a genetic diagnosis for sporadic and syndromic cases. Informative genetic testing serves to clarify future risks for the patient and family members.Recent findingsGenetic discovery in the last decade has identified new PGL/PCC susceptibility loci. We summarize a contemporary approach adopted in our programme for genetic evaluation, testing and prospective management involving biochemical monitoring and imaging for hereditary PGL/PCC. A clinical vignette is presented to illustrate our practice.SummaryCurrent estimates that up to 40% of PGL/PCC are associated with germline mutations have implications for genetic testing recommendations. Prospective management of patients with defined hereditary susceptibility is based on established guidelines for well characterized syndromes. Management of tumour risk for rare syndromes, newly defined genetic associations and undefined genetic susceptibility in the setting of significant family history presents a challenge. Sustained discovery of new PGL/PCC genes underscores the need for a practice of continued genetic evaluation for patients with uninformative results. All patients with PGL/PCC should undergo genetic testing to identify potential hereditary tumour susceptibility. C1 [Rana, Huma Q.; Rainville, Irene R.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Ctr Canc Genet & Prevent,Dept Med Oncol, Boston, MA 02115 USA. [Vaidya, Anand] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Adrenal Disorders,Div Endocrinol Diabet & Hyp, Boston, MA 02115 USA. RP Rana, HQ (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, 450 Brookline Ave, Boston, MA 02115 USA. EM HumaQ_Rana@dfci.harvard.edu OI Rana, Huma/0000-0002-1598-6752 FU NHLBI NIH HHS [L30 HL104553] NR 97 TC 2 Z9 2 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD JUN PY 2014 VL 21 IS 3 BP 166 EP 176 DI 10.1097/MED.0000000000000059 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AG5FS UT WOS:000335445500004 PM 24739310 ER PT J AU Shores, MM Matsumoto, AM AF Shores, Molly M. Matsumoto, Alvin M. TI Testosterone, aging and survival: biomarker or deficiency SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE aging; androgens; biomarker; mortality; testosterone ID LOW SERUM TESTOSTERONE; ALL-CAUSE MORTALITY; CORONARY-HEART-DISEASE; PLACEBO-CONTROLLED TRIALS; ENDOGENOUS SEX-HORMONES; POPULATION-BASED COHORT; LIFE-STYLE FACTORS; QUALITY-OF-LIFE; OLDER MEN; CARDIOVASCULAR-DISEASE AB Purpose of reviewThe purpose of this study is to review recent studies that examined the association of endogenous and exogenous testosterone and mortality in older men.Recent findingsOver the past several years, there has been a steep rise in testosterone prescriptions. The increased use of testosterone occurred in the context of several studies that reported an association between low serum testosterone and increased cardiovascular events and mortality. In contrast, recent studies have reported an association between testosterone treatment and adverse events. A testosterone treatment trial of mobility-impaired elderly men with prevalent cardiovascular disease was stopped due to increased cardiovascular events in the T-treated men and a meta-analysis reported increased cardiovascular events in T-treated men. In two recent large observational studies, testosterone treatment was associated with an increased risk for serious adverse cardiovascular events.SummaryLow testosterone is associated with mortality in multiple cohort studies; however, it is unclear if this is a causal association or due to low testosterone being a biomarker of poor health. Given recent reports of adverse outcomes associated with testosterone treatment, a conservative use of testosterone is warranted in men with cardiovascular disease who may be at greater risk for adverse outcomes. C1 [Shores, Molly M.] VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. [Shores, Molly M.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Matsumoto, Alvin M.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Matsumoto, Alvin M.] GRECC, Seattle, WA USA. RP Shores, MM (reprint author), VA Puget Sound Healthcare Syst, 1660 S Columbian Way,S-116A, Seattle, WA 98108 USA. EM molly.shores@va.gov FU VA Research Service; VA Geriatric Research Education and Clinical Center (GRECC); 1R01 AG042934-01; AbbVie; GSK Pharmaceuticals; Advisory Board for Abbott; Advisory Board for Endo; Forendo Pharmaceuticals; UpToDate. FX The research was supported by the VA Research Service, the VA Geriatric Research Education and Clinical Center (GRECC) and by 1R01 AG042934-01.; Disclosure summary: Dr Matsumoto has the following disclosures to make - Research support from AbbVie and GSK Pharmaceuticals; Advisory Board for Abbott, Endo, and Forendo Pharmaceuticals; and Editor for UpToDate. NR 80 TC 4 Z9 4 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1752-296X EI 1752-2978 J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD JUN PY 2014 VL 21 IS 3 BP 209 EP 216 DI 10.1097/MED.0000000000000057 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA AG5FS UT WOS:000335445500009 PM 24722173 ER PT J AU Brownell, AL AF Brownell, Anna-Liisa TI Prognostic imaging of neuroblastoma SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Editorial Material ID PEDIATRIC NEUROBLASTOMA; DIAGNOSIS; TUMORS; PET C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Expt PET Lab,Athinoula A Martinos Biomed Imaging, Charlestown, MA 02129 USA. RP Brownell, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Expt PET Lab,Athinoula A Martinos Biomed Imaging, Charlestown, MA 02129 USA. EM abrownell@partners.org NR 13 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 EI 1619-7089 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JUN PY 2014 VL 41 IS 6 BP 1043 EP 1045 DI 10.1007/s00259-014-2749-z PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG7BI UT WOS:000335572600001 PM 24668276 ER PT J AU Adriaanse, SM van Dijk, KRA Ossenkoppele, R Reuter, M Tolboom, N Zwan, MD Yaqub, M Boellaard, R Windhorst, AD van der Flier, WM Scheltens, P Lammertsma, AA Barkhof, F van Berckel, BNM AF Adriaanse, Sofie M. van Dijk, Koene R. A. Ossenkoppele, Rik Reuter, Martin Tolboom, Nelleke Zwan, Marissa D. Yaqub, Maqsood Boellaard, Ronald Windhorst, Albert D. van der Flier, Wiesje M. Scheltens, Philip Lammertsma, Adriaan A. Barkhof, Frederik van Berckel, Bart N. M. TI The effect of amyloid pathology and glucose metabolism on cortical volume loss over time in Alzheimer's disease SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE Alzheimer's disease; Amyloid plaques; Hypometabolism; Atrophy; Longitudinal study ID MILD COGNITIVE IMPAIRMENT; 2-YEAR FOLLOW-UP; HIPPOCAMPAL ATROPHY; BETA DEPOSITION; IN-VIVO; A-BETA; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; STRUCTURAL MRI AB Purpose The present multimodal neuroimaging study examined whether amyloid pathology and glucose metabolism are related to cortical volume loss over time in Alzheimer's disease (AD) patients and healthy elderly controls. Methods Structural MRI scans of eleven AD patients and ten controls were available at baseline and follow-up (mean interval 2.5 years). Change in brain structure over time was defined as percent change of cortical volume within seven a-priori defined regions that typically show the strongest structural loss in AD. In addition, two PET scans were performed at baseline: [C-11] PIB to assess amyloid-beta plaque load and [18F]FDG to assess glucose metabolism. [11C] PIB binding and [18F]FDG uptake were measured in the precuneus, a region in which both amyloid deposition and glucose hypometabolism occur early in the course of AD. Results While amyloid-beta plaque load at baseline was not related to cortical volume loss over time in either group, glucose metabolism within the group of AD patients was significantly related to volume loss over time (rho=0.56, p<0.05). Conclusion The present study shows that in a group of AD patients amyloid-beta plaque load as measured by [11C] PIB behaves as a trait marker (i.e., all AD patients showed elevated levels of amyloid, not related to subsequent disease course), whilst hypometabolism as measured by [18F] FDG changed over time indicating that it could serve as a state marker that is predictive of neurodegeneration. C1 [Adriaanse, Sofie M.; Yaqub, Maqsood; Boellaard, Ronald; Windhorst, Albert D.; Lammertsma, Adriaan A.] Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, NL-1007 MB Amsterdam, Netherlands. [van Dijk, Koene R. A.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Adriaanse, Sofie M.; Ossenkoppele, Rik; Tolboom, Nelleke; Zwan, Marissa D.; Barkhof, Frederik; van Berckel, Bart N. M.] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Dept Radiol & Nucl Med, NL-1007 MB Amsterdam, Netherlands. [van Dijk, Koene R. A.; Reuter, Martin] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Reuter, Martin] MIT, Div Hlth Sci & Technol, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [van der Flier, Wiesje M.; Scheltens, Philip] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands. RP Adriaanse, SM (reprint author), Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Dept Radiol & Nucl Med, Neurosci Campus Amsterdam,POB 7057, NL-1007 MB Amsterdam, Netherlands. EM s.adriaanse@vumc.nl RI Reuter, Martin/B-3456-2010; Van Dijk, Koene/G-3317-2012; OI Reuter, Martin/0000-0002-2665-9693; Van Dijk, Koene/0000-0001-6137-4282; Boellaard, Ronald/0000-0002-0313-5686; Windhorst, Albert/0000-0002-1250-7656 FU Internationale Stichting Alzheimer Onderzoek (ISAO) [11539]; Hersenstichting Nederland [KS2011(1)-24] FX This study was sponsored by Internationale Stichting Alzheimer Onderzoek (ISAO; project number #11539) and Hersenstichting Nederland (KS2011(1)-24). NR 57 TC 1 Z9 1 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 EI 1619-7089 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JUN PY 2014 VL 41 IS 6 BP 1190 EP 1198 DI 10.1007/s00259-014-2704-z PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG7BI UT WOS:000335572600017 PM 24615466 ER PT J AU Kroeger, N Choueiri, TK Lee, JL Bjarnason, GA Knox, JJ MacKenzie, MJ Wood, L Srinivas, S Vaishamayan, UN Rha, SY Pal, SK Yuasa, T Donskov, F Agarwal, N Tan, MH Bamias, A Kollmannsberger, CK North, SA Rini, BI Heng, DYC AF Kroeger, Nils Choueiri, Toni K. Lee, Jae-Lyn Bjarnason, Georg A. Knox, Jennifer J. MacKenzie, Mary J. Wood, Lori Srinivas, Sandy Vaishamayan, Ulka N. Rha, Sun-Young Pal, Sumanta K. Yuasa, Takeshi Donskov, Frede Agarwal, Neeraj Tan, Min-Han Bamias, Aristotelis Kollmannsberger, Christian K. North, Scott A. Rini, Brian I. Heng, Daniel Y. C. TI Survival Outcome and Treatment Response of Patients with Late Relapse from Renal Cell Carcinoma in the Era of Targeted Therapy SO EUROPEAN UROLOGY LA English DT Article DE Late recurrence; Targeted therapies; Treatment response; Survival outcome; Renal cell carcinoma ID NEPHRECTOMY; PROGRESSION; FEATURES; CRITERIA; AGE AB Background: A subset of primarily localized renal cell carcinoma (RCC) patients will experience disease recurrence >= 5 yr after initial nephrectomy. Objective: To characterize the clinical outcome of patients with late recurrence beyond 5 yr. Design, setting, and participants: Patients with metastatic RCC (mRCC) treated with targeted therapy were retrospectively characterized according to time to relapse. Relapse was defined as the diagnosis of recurrent metastatic disease > 3 mo after initial curative-intent nephrectomy. Patients with synchronous metastatic disease at presentation were excluded. Patients were classified as early relapsers (ERs) if they recurred within 5 yr; late relapsers (LRs) recurred after 5 yr. Outcome measurements and statistical analysis: Demographics were compared with the Student t test, the chi-square test, or the Fisher exact test. The survival time was estimated with the Kaplan-Meier method, and associations with survival outcome were assessed with univariable and multivariable Cox regression analyses. Results and limitations: Among 1210 mRCC patients treated with targeted therapy after surgery for localized disease, 897 (74%) relapsed within the first 5 yr and 313 (26%) (range: 5-35 yr) after 5 yr. LRs presented with younger age (p < 0.0001), fewer with sarcomatoid features (p < 0.0001), more clear cell histology (p = 0.001), and lower Fuhrman grade (p < 0.0001). Overall objective response rates to targeted therapy were better in LRs versus ERs (31.8% vs 26.5%; p = 0.004). LRs had significantly longer progression-free survival (10.7 mo vs 8.5mo; p = 0.005) and overall survival (OS; 34.0mo vs 27.4 mo; p = 0.004). The study is limited by its retrospective design, noncentralized imaging and pathology review, missing information on metastatectomy, and nonstandardized follow-up protocols. Conclusions: A quarter of patients who eventually developed metastatic disease and were treated with targeted therapy relapsed over 5 yr from initial nephrectomy. LRs have more favorable prognostic features and consequently better treatment response and OS. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 [Kroeger, Nils; Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB T2N 4N2, Canada. [Kroeger, Nils] Univ Med Greifswald, Dept Urol, Greifswald, Germany. [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lee, Jae-Lyn] Univ Ulsan, Coll Med, Asan, South Korea. [Bjarnason, Georg A.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Knox, Jennifer J.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [MacKenzie, Mary J.] London Hlth Sci Ctr, London, ON, Canada. [Wood, Lori] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Srinivas, Sandy] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA. [Vaishamayan, Ulka N.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Rha, Sun-Young] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Seoul, South Korea. [Pal, Sumanta K.] City Hope Comprehens Canc Ctr, Dept Med Oncol & Expt Therapeut, Duarte, CA USA. [Yuasa, Takeshi] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Urol, Tokyo, Japan. [Donskov, Frede] Aarhus Univ Hosp, Dept Oncol, DK-8000 Aarhus, Denmark. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Tan, Min-Han] Natl Canc Ctr, Dept Med Oncol, Singapore, Singapore. [Tan, Min-Han] Inst Bioengn & Nanotechnol, Singapore, Singapore. [Bamias, Aristotelis] Univ Athens, Dept Clin Therapeut, Athens, Greece. [Kollmannsberger, Christian K.] British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. [North, Scott A.] Univ Alberta, Cross Canc Ctr, Edmonton, AB, Canada. [Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, 1331 29th St NW, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca OI Bjarnason, Georg Arnold/0000-0001-6903-5357; Donskov, Frede/0000-0002-8449-863X FU Novartis; Bayer; Pfizer; GlaxoSmithKline; Bayer Korea FX Daniel Y.C. Heng 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: Jae-Lyn Lee receives honoraria from Novartis, Bayer, and Pfizer, and research funding from Bayer. Mary J. MacKenzie is an adviser at Novartis and Pfizer and has received research funding from both. Georg A. Bjarnason is a consultant and adviser for Pfizer. He receives honoraria and research funding from Pfizer. Jennifer J. Knox is a consultant and adviser for AVEO and has received research funding from Pfizer. Lori Wood is an adviser for Pfizer and Novartis and has received research funding from Pfizer, Novartis, and GlaxoSmithKline. Ulka N. Vaishamayan has received honoraria and research funding from Pfizer, Novartis, and GlaxoSmithKline. Sun-Young Rha is an adviser for Novartis, Pfizer, and GlaxoSmithKline and has received research funding from Novartis and Bayer Korea. Frede Donskov has received research funding from Novartis. Christian K. Kollmannsberger is an adviser for Pfizer, Novartis, and GlaxoSmithKline. Scott A North is a consultant and adviser for Novartis, Bayer, GlaxoSmithKline, and Pfizer. Brian I. Rini is an adviser for Pfizer, GlaxoSmithKline, Bayer, and Onyx, and he has received research funding from GlaxoSmithKline and Pfizer. Toni K. Choueiri has received research funding from Pfizer and is an adviser for AVEO, Pfizer, Novartis, GlaxoSmithKline, Genentech, Bayer, and Onyx. Daniel Y.C. Heng is an adviser for AVEO, Pfizer, Novartis, and Bayer. Nils Kroeger, Sandy Srinivas, Sumanta K. Pal, Takeshi Yuasa, Neeraj Agarwal, and Min-Han Tan have nothing to disclose. NR 18 TC 28 Z9 28 U1 0 U2 3 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 JUN PY 2014 VL 65 IS 6 BP 1086 EP 1092 DI 10.1016/j.eururo.2013.07.031 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AG4JV UT WOS:000335386700029 PM 23916693 ER PT J AU Punnen, S Freedland, SJ Presti, JC Aronson, WJ Terris, MK Kane, CJ Amling, CL Carroll, PR Cooperberg, MR AF Punnen, Sanoj Freedland, Stephen J. Presti, Joseph C., Jr. Aronson, William J. Terris, Martha K. Kane, Christopher J. Amling, Christopher L. Carroll, Peter R. Cooperberg, Matthew R. TI Multi-institutional Validation of the CAPRA-S Score to Predict Disease Recurrence and Mortality After Radical Prostatectomy SO EUROPEAN UROLOGY LA English DT Article DE Nomogram; Outcomes; Prostate cancer; Radical prostatectomy ID RANDOMIZED CLINICAL-TRIAL; UNIVERSITY-OF-CALIFORNIA; RISK-ASSESSMENT SCORE; BIOCHEMICAL RECURRENCE; ADJUVANT RADIOTHERAPY; EXTERNAL VALIDATION; CANCER RECURRENCE; SAN-FRANCISCO; MODELS; SURVIVAL AB Background: The University of California, San Francisco, Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score uses pathologic data from radical prostatectomy (RP) to predict prostate cancer recurrence and mortality. However, this clinical tool has never been validated externally. Objective: To validate CAPRA-S in a large, multi-institutional, external database. Design, setting, and participants: The Shared Equal Access Regional Cancer Hospital (SEARCH) database consists of 2892 men who underwent RP from 2001 to 2011. With a median follow-up of 58 mo, 2670men(92%) had complete data to calculate a CAPRA-S score. Intervention: RP. Outcome measurements and statistical analysis: The main outcome was biochemical recurrence. Performance of CAPRA-S in detecting recurrence was assessed and compared with a validated postoperative nomogram by concordance index (c-index), calibration plots, and decision curve analysis. Prediction of cancer-specific mortality was assessed by Kaplan-Meier analysis and the c-index. Results and limitations: The mean age was 62 yr (standard deviation: 6.3), and 34.3% of men had recurrence. The 5-yr progression-free probability for those patients with a CAPRA-S score of 0-2, 3-5, and 6-10 (defining low, intermediate, and high risk) was 72%, 39%, and 17%, respectively. The CAPRA-S c-index was 0.73 in this validation set, compared with a c-index of 0.72 for the Stephenson nomogram. Although CAPRA-S was optimistic in predicting the likelihood of being free of recurrence at 5 yr, it outperformed the Stephenson nomogram on both calibration plots and decision curve analysis. The cindex for predicting cancer-specific mortality was 0.85, with the caveat that this number is based on only 61 events. Conclusions: In this external validation, the CAPRA-S score predicted recurrence and mortality after RP with a c-index > 0.70. The score is an effective prognostic tool that may aid in determining the need for adjuvant therapy. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved. C1 [Punnen, Sanoj; Carroll, Peter R.; Cooperberg, Matthew R.] Univ Calif San Francisco, Dept Urol, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Freedland, Stephen J.] Duke Univ, Dept Surg, Div Urol, Durham, NC USA. [Freedland, Stephen J.] Durham Vet Adm Med Ctr, Urol Sect, Durham, NC USA. [Presti, Joseph C., Jr.] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. [Presti, Joseph C., Jr.] Vet Adm Med Ctr, Dept Surg, Urol Sect, Palo Alto, CA 94304 USA. [Aronson, William J.] Vet Adm Greater Los Angeles Healthcare Syst, Urol Sect, Dept Surg, Los Angeles, CA USA. [Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Terris, Martha K.] Vet Adm Med Ctr, Dept Surg, Urol Sect, Augusta, GA 30904 USA. [Terris, Martha K.] Med Coll Georgia, Dept Surg, Augusta, GA 30912 USA. [Kane, Christopher J.] Univ Calif San Diego, Dept Urol, San Diego, CA 92103 USA. [Amling, Christopher L.] Oregon Hlth & Sci Univ, Dept Urol, Portland, OR USA. [Cooperberg, Matthew R.] Vet Adm Med Ctr, Dept Surg, Urol Sect, San Francisco, CA 94121 USA. RP Cooperberg, MR (reprint author), Univ Calif San Francisco, Dept Urol, 1600 Divisadero St,Box 1695, San Francisco, CA 94143 USA. EM mcooperberg@urology.ucsf.edu OI Terris, Martha/0000-0002-3843-7270 FU US Department of Veterans Affairs; US Department of Defense; Prostate Cancer Research Program; NIH [R01CA100938]; NIH Specialized Programs of Research Excellence [P50 CA92131-01A1]; Georgia Cancer Coalition; American Urological Association Foundation/Astellas Rising Star in Urology Award FX Funding for the collection and management of the data was from the US Department of Veterans Affairs, the US Department of Defense, Prostate Cancer Research Program (C.J.K., S.J.F), NIH R01CA100938 (W.J.A), NIH Specialized Programs of Research Excellence Grant P50 CA92131-01A1 (W.J.A), Georgia Cancer Coalition (M.K.T), and the American Urological Association Foundation/Astellas Rising Star in Urology Award (S.J.E). Views and opinions of and endorsements by the authors do not reflect thsoe of the US Army or the Department of Defense. NR 26 TC 40 Z9 41 U1 1 U2 4 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 JUN PY 2014 VL 65 IS 6 BP 1171 EP 1177 DI 10.1016/j.eururo.2013.03.058 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA AG4JV UT WOS:000335386700044 PM 23587869 ER PT J AU Han, LC Delpe, S Shah, ND Ziegenfuss, JY Tilburt, JC Karnes, RJ Nguyen, PL Gross, CP Yu, JB Trinh, QD Sun, M Ranasinghe, WKB Kim, SP AF Han, Leona C. Delpe, Sophia Shah, Nilay D. Ziegenfuss, Jeanette Y. Tilburt, Jon C. Karnes, R. Jeffrey Nguyen, Paul L. Gross, Cary P. Yu, James B. Quoc-Dien Trinh Sun, Maxine Ranasinghe, Weranja K. B. Kim, Simon P. TI Perceptions of Radiation Oncologists and Urologists on Sources and Type of Evidence to Inform Prostate Cancer Treatment Decisions SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID RADICAL PROSTATECTOMY; LOW-RISK; RANDOMIZED-TRIAL; MANAGEMENT; TRENDS; GUIDELINES; ADJUVANT AB Purpose: To perform a national survey of radiation oncologists and urologists about the type of resources used and the level of evidence needed to change clinical practice in localized prostate cancer. Methods and Materials: From a random sample, 1422 physicians were mailed a survey assessing the types of information used and what level of evidence could alter their clinical practice in prostate cancer. Multivariable logistic regression models were used to identify differences in physician characteristics for each outcome. Results: Survey response rates were similar for radiation oncologists and urologists (44% vs 46%; P=.46). Specialty-specific journals represented the most commonly used resource for informing the clinical practice for radiation oncologists (65%) and urologists (70%). Relative to radiation oncologists, urologists were less likely to report utilizing top-tier medical journals (25% vs 39%; adjusted odds ratio [OR] 0.50; P=.01) or cancer journals (22% vs 51%; adjusted OR 0.50; P <.001) but more likely to rely on clinical guidelines (46% vs 38%; adjusted OR 1.6; P=.006). Both radiation oncologists and urologists most commonly reported large randomized, clinical trials as the level of evidence to change treatment recommendations for localized prostate cancer ( 85% vs 77%; P=.009). Conclusions: Both specialties rely on their own specialty-specific journals and view randomized, clinical trials as the level of evidence needed to change clinical practice. Our study provides a context on meaningful ways of disseminating evidence for localized prostate cancer. (C) 2014 Elsevier Inc. C1 [Han, Leona C.; Shah, Nilay D.] Mayo Clin, Div Hlth Care Policy & Res, Rochester, MN USA. [Delpe, Sophia; Kim, Simon P.] Yale Univ, Dept Urol, New Haven, CT 06517 USA. [Ziegenfuss, Jeanette Y.] HealthPartners, Minneapolis, MN USA. [Tilburt, Jon C.] Mayo Clin, Knowledge & Evaluat Res Unit, Rochester, MN USA. [Tilburt, Jon C.] Mayo Clin, Biomed Eth Program, Rochester, MN USA. [Tilburt, Jon C.] Mayo Clin, Div Gen Internal Med, Rochester, MN USA. [Karnes, R. Jeffrey] Mayo Clin, Dept Urol, Rochester, MN USA. [Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Radiat Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Gross, Cary P.; Yu, James B.; Kim, Simon P.] Yale Univ, Canc Outcomes & Publ Policy Effectiveness Res Ctr, New Haven, CT 06517 USA. [Gross, Cary P.] Yale Univ, Dept Internal Med, New Haven, CT 06517 USA. [Yu, James B.] Yale Univ, Dept Radiat Oncol, New Haven, CT 06517 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. [Sun, Maxine] Univ Montreal, Ctr Hlth, Montreal, PQ, Canada. [Ranasinghe, Weranja K. B.] Alfred Hosp, Div Urol, Melbourne, Vic, Australia. RP Kim, SP (reprint author), Yale Univ, Dept Urol, 310 Cedar St,BML 238B, New Haven, CT 06517 USA. EM simkim@me.com NR 29 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 1 PY 2014 VL 89 IS 2 BP 277 EP 283 DI 10.1016/j.ijrobp.2014.02.001 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AG6FG UT WOS:000335513800010 PM 24685153 ER PT J AU Hattangadi-Gluth, JA Chapman, PH Kim, D Niemierko, A Bussiere, MR Stringham, A Daartz, J Ogilvy, C Loeffler, JS Shih, HA AF Hattangadi-Gluth, Jona A. Chapman, Paul H. Kim, Daniel Niemierko, Andrzej Bussiere, Marc R. Stringham, Alison Daartz, Juliane Ogilvy, Christopher Loeffler, Jay S. Shih, Helen A. TI Single-Fraction Proton Beam Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID GAMMA-KNIFE SURGERY; TERM-FOLLOW-UP; GRADING SYSTEM; BRAIN-STEM; OBLITERATION; THALAMUS; COMPLICATIONS; RADIATION; OUTCOMES; THERAPY AB Purpose/Objective(s): To evaluate the obliteration rate and potential adverse effects of single-fraction proton beam stereotactic radiosurgery (PSRS) in patients with cerebral arteriovenous malformations (AVMs). Methods and Materials: From 1991 to 2010, 248 consecutive patients with 254 cerebral AVMs received single-fraction PSRS at our institution. The median AVM nidus volume was 3.5 cc (range, 0.1-28.1 cc), 23% of AVMs were in critical/deep locations (basal ganglia, thalamus, or brainstem), and the most common prescription dose was 15 Gy(relative biological effectiveness [RBE]). Univariable and multivariable analyses were performed to assess factors associated with obliteration and hemorrhage. Results: At a median follow-up time of 35 months (range, 6-198 months), 64.6% of AVMs were obliterated. The median time to total obliteration was 31 months (range, 6-127 months), and the 5-year and 10-year cumulative incidence of total obliteration was 70% and 91%, respectively. On univariable analysis, smaller target volume (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.86-0.93, P <.0001), smaller treatment volume (HR 0.93, 95% CI 0.90-0.96, P <.0001), higher prescription dose (HR 1.16, 95% CI 1.07-1.26, P=.001), and higher maximum dose (HR 1.14, 95% CI 1.05-1.23, P=.002) were associated with total obliteration. Deep/critical location was also associated with decreased likelihood of obliteration (HR 0.68, 95% CI 0.47-0.98, P=.04). On multivariable analysis, critical location (adjusted HR [AHR] 0.42, 95% CI 0.27-0.65, P <.001) and smaller target volume (AHR 0.81, 95% CI 0.68-0.97, P=.02) remained associated with total obliteration. Posttreatment hemorrhage occurred in 13 cases (5-year cumulative incidence of 7%), all among patients with less than total obliteration, and 3 of these events were fatal. The most common complication was seizure, controlled with medications, both acutely (8%) and in the long term (9.1%). Conclusions: The current series is the largest modern series of PSRS for cerebral AVMs. PSRS can achieve a high obliteration rate with minimal morbidity. Posttreatment hemorrhage remains a potentially fatal risk among patients who have not yet responded to treatment. (C) 2014 Elsevier Inc. C1 [Hattangadi-Gluth, Jona A.] Univ Calif San Diego, Dept Radiat Med & Appl Sci, San Diego, CA 92103 USA. [Chapman, Paul H.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kim, Daniel; Niemierko, Andrzej; Bussiere, Marc R.; Stringham, Alison; Daartz, Juliane; Loeffler, Jay S.; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ogilvy, Christopher] Beth Israel Deaconess Med Ctr, Dept Neurosurg, Boston, MA 02215 USA. RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM hshih@partners.org NR 34 TC 7 Z9 7 U1 0 U2 5 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 JUN 1 PY 2014 VL 89 IS 2 BP 338 EP 346 DI 10.1016/j.ijrobp.2014.02.030 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AG6FG UT WOS:000335513800017 PM 24726288 ER PT J AU Grassberger, C Daartz, J Dowdell, S Ruggieri, T Sharp, G Paganetti, H AF Grassberger, Clemens Daartz, Juliane Dowdell, Stephen Ruggieri, Thomas Sharp, Greg Paganetti, Harald TI Quantification of Proton Dose Calculation Accuracy in the Lung SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID PENCIL BEAM ALGORITHM; MONTE-CARLO; HETEROGENEOUS MEDIA; THERAPY; CANCER; RADIOTHERAPY; TUMORS; OUTCOMES; PHOTON; ISSUES AB Purpose: To quantify the accuracy of a clinical proton treatment planning system (TPS) as well as Monte Carlo (MC)-based dose calculation through measurements and to assess the clinical impact in a cohort of patients with tumors located in the lung. Methods and Materials: A lung phantom and ion chamber array were used to measure the dose to a plane through a tumor embedded in the lung, and to determine the distal fall-off of the proton beam. Results were compared with TPS and MC calculations. Dose distributions in 19 patients (54 fields total) were simulated using MC and compared to the TPS algorithm. Results: MC increased dose calculation accuracy in lung tissue compared with the TPS and reproduced dose measurements in the target to within +/- 2%. The average difference between measured and predicted dose in a plane through the center of the target was 5.6% for the TPS and 1.6% for MC. MC recalculations in patients showed a mean dose to the clinical target volume on average 3.4% lower than the TPS, exceeding 5% for small fields. For large tumors, MC also predicted consistently higher V5 and V10 to the normal lung, because of a wider lateral penumbra, which was also observed experimentally. Critical structures located distal to the target could show large deviations, although this effect was highly patient specific. Range measurements showed that MC can reduce range uncertainty by a factor of similar to 2: the average (maximum) difference to the measured range was 3.9 mm (7.5 mm) for MC and 7 mm (17 mm) for the TPS in lung tissue. Conclusion: Integration of Monte Carlo dose calculation techniques into the clinic would improve treatment quality in proton therapy for lung cancer by avoiding systematic overestimation of target dose and underestimation of dose to normal lung. In addition, the ability to confidently reduce range margins would benefit all patients by potentially lowering toxicity. (C) 2014 Elsevier Inc. C1 [Grassberger, Clemens; Daartz, Juliane; Dowdell, Stephen; Ruggieri, Thomas; Sharp, Greg; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Grassberger, Clemens; Daartz, Juliane; Dowdell, Stephen; Ruggieri, Thomas; Sharp, Greg; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Grassberger, Clemens] Paul Scherrer Inst, Ctr Proton Radiotherapy, Villigen, Switzerland. RP Grassberger, C (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM Grassberger.Clemens@mgh.harvard.edu FU National Cancer Institute [R01CA111590] FX Supported by National Cancer Institute grant R01CA111590. NR 25 TC 10 Z9 10 U1 0 U2 6 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 JUN 1 PY 2014 VL 89 IS 2 BP 424 EP 430 DI 10.1016/j.ijrobp.2014.02.023 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA AG6FG UT WOS:000335513800028 PM 24726289 ER PT J AU Lichtenhan, JT Hartsock, JJ Gill, RM Guinan, JJ Salt, AN AF Lichtenhan, J. T. Hartsock, J. J. Gill, R. M. Guinan, J. J., Jr. Salt, A. N. TI The Auditory Nerve Overlapped Waveform (ANOW) Originates in the Cochlear Apex SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE auditory nerve neurophonic; compound action potential; low-frequency hearing; neural synchrony; phase locking ID GUINEA-PIG; LOW-FREQUENCY; ROUND WINDOW; TRANSMITTER RELEASE; HAIR-CELLS; INNER-EAR; HEARING; PERILYMPH; SYNAPSE; FIBERS AB Measurements of cochlear function with compound action potentials (CAPs), auditory brainstem responses, and otoacoustic emissions work well with high-frequency sounds but are problematic at low frequencies. We have recently shown that the auditory nerve overlapped waveform (ANOW) can objectively quantify low-frequency (< 1 kHz) auditory sensitivity, as thresholds for ANOW at low frequencies and for CAP at high frequencies relate similarly to single auditory nerve fiber thresholds. This favorable relationship, however, does not necessarily mean that ANOW originates from auditory nerve fibers innervating low-frequency regions of the cochlear apex. In the present study, we recorded the cochlear response to tone bursts of low frequency (353, 500, and 707 Hz) and high frequency (2 to 16 kHz) during administration of tetrodotoxin (TTX) to block neural function. TTX was injected using a novel method of slow administration from a pipette sealed into the cochlear apex, allowing real-time measurements of systematic neural blocking from apex to base. The amplitude of phase-locked (ANOW) and onset (CAP) neural firing to moderate-level, low-frequency sounds were markedly suppressed before thresholds and responses to moderate-level, high-frequency sounds were affected. These results demonstrate that the ANOW originates from responses of auditory nerve fibers innervating cochlear apex, confirming that ANOW provides a valid physiological measure of low-frequency auditory nerve function. C1 [Lichtenhan, J. T.; Hartsock, J. J.; Gill, R. M.; Salt, A. N.] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. [Guinan, J. J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Guinan, J. J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lichtenhan, JT (reprint author), Washington Univ, Sch Med, Dept Otolaryngol, Box 8115660 South Euclid Ave, St Louis, MO 63110 USA. EM jlichtenhan@gmail.com FU National Institutes of Health, National Institute on Deafness and Other Communication Disorders [R03 DC012844, R01 DC000235, R01 DC001368] FX We thank Doctors Ann E. Hickox, Mark A. Rutherford, Christopher A. Shera, and Mrs. Uzma S. Wilson for helpful discussion on this research. Two anonymous reviewers and Associate Editor Dr. Nigel Cooper provided productive criticisms that improved this report. This work was supported by grants R03 DC012844 (J.T.L.), R01 DC000235 (J.J.G.), and R01 DC001368 (A.N.S.) from the National Institutes of Health, National Institute on Deafness and Other Communication Disorders. NR 44 TC 11 Z9 11 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 EI 1438-7573 J9 JARO-J ASSOC RES OTO JI JARO PD JUN PY 2014 VL 15 IS 3 BP 395 EP 411 DI 10.1007/s10162-014-0447-y PG 17 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA AH0LN UT WOS:000335811500005 PM 24515339 ER PT J AU Vaina, LM Soloviev, S Calabro, FJ Buonanno, F Passingham, R Cowey, A AF Vaina, Lucia M. Soloviev, Sergei Calabro, Finnegan J. Buonanno, Ferdinando Passingham, Richard Cowey, Alan TI Reorganization of Retinotopic Maps after Occipital Lobe Infarction SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID HUMAN CEREBRAL-CORTEX; HUMAN VISUAL-CORTEX; PRIMATE SOMATOSENSORY CORTEX; PERIPHERAL-NERVE INJURY; SURFACE-BASED ANALYSIS; NEW-WORLD MONKEYS; MOTION PERCEPTION; STRIATE CORTEX; FUNCTIONAL REORGANIZATION; ISCHEMIC LESIONS AB We studied patient JS, who had a right occipital infarct that encroached on visual areas V1, V2v, and VP. When tested psychophysically, he was very impaired at detecting the direction of motion in random dot displays where a variable proportion of dots moving in one direction (signal) were embedded in masking motion noise (noise dots). The impairment on this motion coherence task was especially marked when the display was presented to the upper left (affected) visual quadrant, contralateral to his lesion. However, with extensive training, by 11 months his threshold fell to the level of healthy participants. Training on the motion coherence task generalized to another motion task, the motion discontinuity task, on which he had to detect the presence of an edge that was defined by the difference in the direction of the coherently moving dots (signal) within the display. He was much better at this task at 8 than 3 months, and this improvement was associated with an increase in the activation of the human MT complex (hMT(+)) and in the kinetic occipital region as shown by repeated fMRI scans. We also used fMRI to perform retinotopic mapping at 3, 8, and 11 months after the infarct. We quantified the retinotopy and areal shifts by measuring the distances between the center of mass of functionally defined areas, computed in spherical surface-based coordinates. The functionally defined retinotopic areas V1, V2v, V2d, and VP were initially smaller in the lesioned right hemisphere, but they increased in size between 3 and 11 months. This change was not found in the normal, left hemisphere of the patient or in either hemispheres of the healthy control participants. We were interested in whether practice on the motion coherence task promoted the changes in the retinotopic maps. We compared the results for patient JS with those from another patient (PF) who had a comparable lesion but had not been given such practice. We found similar changes in the maps in the lesioned hemisphere of PF. However, PF was only scanned at 3 and 7 months, and the biggest shifts in patient JS were found between 8 and 11 months. Thus, it is important to carry out a prospective study with a trained and untrained group so as to determine whether the patterns of reorganization that we have observed can be further promoted by training. C1 [Vaina, Lucia M.; Buonanno, Ferdinando] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vaina, Lucia M.; Buonanno, Ferdinando] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Vaina, Lucia M.; Soloviev, Sergei; Calabro, Finnegan J.; Buonanno, Ferdinando; Cowey, Alan] Boston Univ, Boston, MA 02215 USA. [Passingham, Richard; Cowey, Alan] Univ Oxford, Oxford OX1 2JD, England. RP Vaina, LM (reprint author), Boston Univ, Dept Biomed, Room 315,44 Cummington St, Boston, MA 02215 USA. EM vaina@bu.edu OI Calabro, Finnegan/0000-0002-8092-3942 FU NIH [R01NS064100] FX This work was supported by NIH grant R01NS064100 to L. M. V. Lucia M. Vaina dedicates this article to Charlie Gross, who has been a long-time collaborator and friend. I met him at the INS meeting in Beaune (France), and since then we often discussed the relationship between several aspects of high-level visual processing described in his work in monkeys physiology and my work in neuropsychology. In particular, his pioneering study of biological motion in monkeys' superior temporal lobe has influenced my own work on biological motion and has led us to coauthor a paper on this topic. Working with Charlie was a uniquely enjoyable experience. Alan Cowey and I often spoke fondly about Charlie, a dear friend and close colleague to us both, whose work, exquisite sense of humor, and unbound zest of living we both deeply admired and loved. NR 58 TC 3 Z9 3 U1 0 U2 12 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X EI 1530-8898 J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUN PY 2014 VL 26 IS 6 SI SI BP 1266 EP 1282 DI 10.1162/jocn_a_00538 PG 17 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA AG6CM UT WOS:000335506100007 PM 24345177 ER PT J AU Noh, GT Kim, MH Suh, JY Song, Y Lee, CK Baek, JH Lee, YS Cho, G Kim, E Kim, YR Cho, HJ Lim, D Kim, JK AF Noh, Gwang Tae Kim, Mi-hyun Suh, Ji-Yeon Song, Youngkyu Lee, Chang Kyung Baek, Jin Hee Lee, Yong Seok Cho, Gyunggoo Kim, EunJu Kim, Young Ro Cho, Hyung Joon Lim, Dongyeol Kim, Jeong Kon TI Sunitinib-CLIO Conjugate: A VEGFR/PDGFR-Targeting Active MR Probe SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE MR probe; VEGFR; PDGFR; Iron oxide; Angiogenesis ID IRON-OXIDE NANOPARTICLES; CONTRAST AGENTS; INHIBITOR; THERAPY; ANGIOGENESIS; SORAFENIB; SU11248 AB This study was conducted to evaluate feasibility of sunitinib-CLIO conjugate as a vascular endothelial growth factor receptor/platelet-derived growth factor receptor (VEGFR/PDGFR)-specific magnetic resonance (MR) probe. VEGFR/PDGFR-targeting MR probe was synthesized by conjugating cross-linked iron-oxide (CLIO) with tyrosine-kinase inhibitor (sunitinib). In VEGFR/PDGFR-positive (U118MG) and VEGFR/PDGFR-negative (HT29) cells and tumor models, conjugate-driven Delta R (2) was estimated, while CLIO was used as control. Prussian-blue staining was performed for quantifying the amount of tumor-binding conjugates. Delta R (2) between sunitinib-CLIO-treated and non-treated cells was greater in U118MG (mean, 2.1/s) than in HT29 cells (1.0/s). In in vivo study, conjugate induced a greater Delta R (2) in U118MG (11.2/s) than HT29 tumors (5.9/s). Conjugate-induced R (2) changes were not correlated with degree of Gd-DTPA enhancement, demonstrating that tumor binding of sunitinib-CLIO was independent of enhanced permeability and retention effect. % area of Prussian-blue staining was greater in U118MG (8.5 %) than in HT29 (1.4 %). Sunitinib-CLIO conjugate can be used as an active MR probe for quantifying VEGFR/PDGFR. C1 [Noh, Gwang Tae; Lim, Dongyeol] Sejong Univ, Dept Chem, Seoul 143747, South Korea. [Kim, Mi-hyun; Suh, Ji-Yeon; Lee, Chang Kyung; Baek, Jin Hee; Lee, Yong Seok; Kim, Jeong Kon] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol,Res Inst Radiol, Seoul 138736, South Korea. [Suh, Ji-Yeon; Song, Youngkyu; Lee, Chang Kyung; Baek, Jin Hee; Lee, Yong Seok; Cho, Gyunggoo; Kim, Jeong Kon] Korea Basic Sci Inst, Div Magnet Resonance, Ochang 363883, Chungbuk, South Korea. [Kim, EunJu] Philips Healthcare, Seoul 260199, South Korea. [Kim, Young Ro] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Cho, Hyung Joon] Ulsan Natl Inst Sci & Technol, Ulsan 689798, South Korea. RP Kim, JK (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Radiol,Res Inst Radiol, 388-1 Poongnap Dong, Seoul 138736, South Korea. EM kim.jeongkon@gmail.com FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2010-0015389, 2011-0028826]; Korea Basic Science Institute [T3222K] FX This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0015389 and 2011-0028826) and by a grant from Korea Basic Science Institute (T3222K). We specially thank to Dr. Eun Kyoung Ryu for manuscript preparation. NR 18 TC 2 Z9 2 U1 1 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JUN PY 2014 VL 16 IS 3 BP 340 EP 349 DI 10.1007/s11307-013-0697-9 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG9JH UT WOS:000335734900006 PM 24185817 ER PT J AU Tichauer, KM Deharvengt, SJ Samkoe, KS Gunn, JR Bosenberg, MW Turk, MJ Hasan, T Stan, RV Pogue, BW AF Tichauer, Kenneth M. Deharvengt, Sophie J. Samkoe, Kimberley S. Gunn, Jason R. Bosenberg, Marcus W. Turk, Mary-Jo Hasan, Tayyaba Stan, Radu V. Pogue, Brian W. TI Tumor Endothelial Marker Imaging in Melanomas Using Dual-Tracer Fluorescence Molecular Imaging SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE Tracer kinetic modeling; Cancer; Mouse model; PV1 ID IN-VIVO; FENESTRATED ENDOTHELIA; COMPARTMENTAL MODEL; RECEPTOR; BINDING; EXPRESSION; DIAPHRAGMS; KINETICS; ANTIBODY; CANCER AB Cancer-specific endothelial markers available for intravascular binding are promising targets for new molecular therapies. In this study, a molecular imaging approach of quantifying endothelial marker concentrations (EMCI) is developed and tested in highly light-absorbing melanomas. The approach involves injection of targeted imaging tracer in conjunction with an untargeted tracer, which is used to account for nonspecific uptake and tissue optical property effects on measured targeted tracer concentrations. Theoretical simulations and a mouse melanoma model experiment were used to test out the EMCI approach. The tracers used in the melanoma experiments were fluorescently labeled anti-Plvap/PV1 antibody (plasmalemma vesicle associated protein Plvap/PV1 is a transmembrane protein marker exposed on the luminal surface of endothelial cells in tumor vasculature) and a fluorescent isotype control antibody, the uptakes of which were measured on a planar fluorescence imaging system. The EMCI model was found to be robust to experimental noise under reversible and irreversible binding conditions and was capable of predicting expected overexpression of PV1 in melanomas compared to healthy skin despite a 5-time higher measured fluorescence in healthy skin compared to melanoma: attributable to substantial light attenuation from melanin in the tumors. This study demonstrates the potential of EMCI to quantify endothelial marker concentrations in vivo, an accomplishment that is currently unavailable through any other methods, either in vivo or ex vivo. C1 [Tichauer, Kenneth M.] IIT, Dept Biomed Engn, Chicago, IL 60616 USA. [Deharvengt, Sophie J.; Stan, Radu V.] Geisel Sch Med Dartmouth, Dept Pathol, Hanover, NH 03755 USA. [Samkoe, Kimberley S.; Pogue, Brian W.] Geisel Sch Med Dartmouth, Dept Surg, Hanover, NH 03755 USA. [Turk, Mary-Jo; Stan, Radu V.] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Hanover, NH 03755 USA. [Samkoe, Kimberley S.; Gunn, Jason R.; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Bosenberg, Marcus W.] Yale Univ, New Haven, CT 06520 USA. [Turk, Mary-Jo; Pogue, Brian W.] Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Hasan, Tayyaba; Pogue, Brian W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Tichauer, KM (reprint author), IIT, Dept Biomed Engn, Chicago, IL 60616 USA. EM tichauer@iit.edu RI Stan, Radu/E-8876-2011 OI Stan, Radu/0000-0003-2969-1725 FU NIH [R01 CA109558, U54 CA151662, R21 CA175592]; CIHR FX This work was sponsored by NIH research grants R01 CA109558, U54 CA151662, and R21 CA175592, as well as a CIHR Postdoctoral Fellowship for KMT. NR 35 TC 6 Z9 6 U1 0 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 EI 1860-2002 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD JUN PY 2014 VL 16 IS 3 BP 372 EP 382 DI 10.1007/s11307-013-0692-1 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AG9JH UT WOS:000335734900009 PM 24217944 ER PT J AU Clarke, SE Kang, JX Ma, DWL AF Clarke, Shannon E. Kang, Jing X. Ma, David W. L. TI The iFat1 transgene permits conditional endogenous n-3 PUFA enrichment both in vitro and in vivo SO TRANSGENIC RESEARCH LA English DT Article DE fat-1; n-3 Desaturase; Cre-recombinase; loxP ID FATTY-ACID DESATURASE; ADENOVIRAL GENE-TRANSFER; FAT-1 MICE; CANCER CELLS; HPRT LOCUS; EXPRESSION; MOUSE; RATIO; RECOMBINATION; GENERATION AB Fat-1 transgenic mice, which endogenously convert n-6 PUFA to n-3 PUFA, are a useful tool in health research; however with this model timing of n-3 PUFA enrichment cannot be directly controlled. To add such capability, the novel Cre-recombinase inducible fat-1 (iFat1) transgenic mouse has been developed. The aim of this study was to characterize the utility of the iFat1 transgene as a model of Cre-inducible endogenous n-3 PUFA enrichment. Functionality of the iFat1 transgene was screened both in vitro and in vivo. In the presence of Cre, the iFat1 transgene resulted in a balancing (p < 0.01) of the n-6/n-3 PUFA ratio within phospholipids in the human embryonic kidney 293T cell line. For in vivo analysis, iFat1 transgenic mice were crossed with the R26-Cre-ERT2 (Tam-Cre) mouse line, a tamoxifen inducible Cre-expression model. Tam-Cre/iFat1 double hybrids were transiently treated with tamoxifen at 6-7 weeks, then terminated 3 weeks later. Tamoxifen treated mice had increased (p < 0.05) tissue n-3 PUFA and a parts per thousand yentwo-fold reduction (p < 0.05) in the n-6/n-3 PUFA ratio of liver, kidney and muscle phospholipids relative to vehicle treated controls. Collectively these findings suggest that the iFat1 transgenic mouse may be a promising tool to help elucidate the temporal effects through which n-3 PUFA impacts health related outcomes. C1 [Clarke, Shannon E.; Ma, David W. L.] Univ Guelph, Dept Human Hlth & Nutr Sci, Guelph, ON N1G 2W1, Canada. [Kang, Jing X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. RP Ma, DWL (reprint author), Univ Guelph, Dept Human Hlth & Nutr Sci, 50 Stone Rd East, Guelph, ON N1G 2W1, Canada. EM davidma@uoguelph.ca FU Canadian Institutes of Health Research [89971]; Canada Foundation for Innovation Leaders Opportunity Fund; Ontario Research Fund; Canadian Institute of Health Research Federick Banting; Canadian Institute of Charles Best Canada Graduate Scholarship FX This work was supported by the Canadian Institutes of Health Research (Grant #89971 to D. W. L. Ma) and the Canada Foundation for Innovation Leaders Opportunity Fund with matching from the Ontario Research Fund. S. E. Clarke is funded by a Canadian Institutes of Health Research Federick Banting and Charles Best Canada Graduate Scholarship. The authors would like to acknowledge Lyn Hillyer and Colin Stringer for their technical assistance in this as well as Dr. Nina Jones (Department of Molecular and Cellular Biology, University of Guelph) for provision of the HEK 293T and expertise in the in vitro experiments. NR 39 TC 2 Z9 2 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-8819 EI 1573-9368 J9 TRANSGENIC RES JI Transgenic Res. PD JUN PY 2014 VL 23 IS 3 BP 489 EP 501 DI 10.1007/s11248-014-9788-x PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA AH0SV UT WOS:000335831600008 PM 24622775 ER PT J AU Byers, AL Yaffe, K AF Byers, Amy L. Yaffe, Kristine TI Depression and dementias among military veterans SO ALZHEIMERS & DEMENTIA LA English DT Article DE Dementia; Alzheimer's disease; Cognitive impairment; Depression; Posttraumatic stress disorder; Traumatic brain injury; Older veterans ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; MILD COGNITIVE IMPAIRMENT; LATE-LIFE DEPRESSION; WHITE-MATTER HYPERINTENSITIES; CARDIOVASCULAR RISK-FACTORS; ALZHEIMERS-DISEASE; HIPPOCAMPAL VOLUME; MAJOR DEPRESSION; GERIATRIC DEPRESSION AB Depression is very common throughout the course of veterans' lives, and dementia is common in late life. Previous studies suggest an association between depression and dementia in military veterans. The most likely biologic mechanisms that may link depression and dementia among military veterans include vascular disease, changes in glucocorticoid steroids and hippocampal atrophy, deposition of beta-amyloid plaques, inflammatory changes, and alterations of nerve growth factors. In addition, military veterans often have depression comorbid with posttraumatic stress disorder or traumatic brain injury. Therefore, in military veterans, these hypothesized biologic pathways going from depression to dementia are more than likely influenced by trauma-related processes. Treatment strategies for depression, posttraumatic stress disorder, or traumatic brain injury could alter these pathways and as a result decrease the risk for dementia. Given the projected increase of dementia, as well as the projected increase in the older segment of the veteran population, in the future, it is critically important that we understand whether treatment for depression alone or combined with other regimens improves cognition. In this review, we summarize the principal mechanisms of this relationship and discuss treatment implications in military veterans. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Byers, Amy L.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Byers, Amy L.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Byers, AL (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. EM Amy.Byers@ucsf.edu FU United States Army Medical Research and Materiel Command FX Publication of this article was supported by the United States Army Medical Research and Materiel Command. NR 114 TC 5 Z9 5 U1 5 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2014 VL 10 IS 3 SU 1 BP S166 EP S173 DI 10.1016/j.jalz.2014.04.007 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA CP8GM UT WOS:000360130700011 PM 24924668 ER PT J AU Durazzo, TC Mattsson, N Weiner, MW AF Durazzo, Timothy C. Mattsson, Niklas Weiner, Michael W. CA Alzheimer's Dis Neuroimaging TI Smoking and increased Alzheimer's disease risk: A review of potential mechanisms SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; Cigarette smoking; Tobacco; Risk; Amyloid; Tau; Military; Oxidative stress; US Armed Services ID CHRONIC CIGARETTE-SMOKING; MILD COGNITIVE IMPAIRMENT; ALCOHOL-DEPENDENT INDIVIDUALS; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL AMYLOID ANGIOPATHY; NICOTINIC ACETYLCHOLINE-RECEPTOR; TRAUMATIC BRAIN-INJURY; PITTSBURGH COMPOUND-B; FREE-RADICAL DAMAGE; STRESS IN-VIVO AB Background: Cigarette smoking has been linked with both increased and decreased risk for Alzheimer's disease (AD). This is relevant for the US military because the prevalence of smoking in the military is approximately 11% higher than in civilians. Methods: A systematic review of published studies on the association between smoking and increased risk for AD and preclinical and human literature on the relationships between smoking, nicotine exposure, and AD-related neuropathology was conducted. Original data from comparisons of smoking and never-smoking cognitively normal elders on in vivo amyloid imaging are also presented. Results: Overall, literature indicates that former/active smoking is related to a significantly increased risk for AD. Cigarette smoke/smoking is associated with AD neuropathology in preclinical models and humans. Smoking-related cerebral oxidative stress is a potential mechanism promoting AD pathology and increased risk for AD. Conclusions: A reduction in the incidence of smoking will likely reduce the future prevalence of AD. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA. [Durazzo, Timothy C.; Mattsson, Niklas; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Mattsson, Niklas] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Clin Neurochem Lab, Molndal, Sweden. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, CIND, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU National Institutes of Health [NIH DA24136, P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435]; ADNI; National Institute on Aging [U01 AG024904]; National Institute of Biomedical Imaging and Bioengineering; Dana Foundation FX T.C.D. was responsible for the concept and design of the review, completed all statistical analyses on the original data presented, and wrote the original and revised versions of the manuscript. N.M. and M.W.W. were involved in manuscript editing, data interpretation, and manuscript draft revisions. T.C.D. had full access to all the original data presented study and takes responsibility for the integrity of the data and the accuracy of the data analyses. This work was supported by the National Institutes of Health (NIH DA24136 to T.C.D.) and by the use of resources and facilities at the San Francisco Veterans Administration Medical Center. Florbetapir data collection and sharing for this project was funded by ADNI. ADNI is funded by the National Institute on Aging (U01 AG024904), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; GlaxoSmithKline; Innogenetics; Johnson and Johnson; Eli Lilly and Co.; Medpace, Inc.; Merck and Co., Inc.; Novartis AG; Pfizer Inc; F. Hoffman-La Roche; Schering-Plough; Synarc, Inc.; and Wyeth, as well as nonprofit partners such as the Alzheimer's Association and Alzheimer Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org; http://www.fnih.org; http://www.fnih.org; http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University Southern California. This research was also supported by National Institutes of Health grants P30 AG010129, K01 AG030514, R01 AG010897, and R01 AG012435, and The Dana Foundation and by resources by resources and the use of facilities at the San Francisco Veterans Administration Medical Center, San Francisco, CA. The aforementioned funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. Original data used in preparation of this article were obtained from the ADNI database (www.loni.usc.edu/ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Authorship _List. pdf NR 260 TC 39 Z9 41 U1 5 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2014 VL 10 IS 3 SU 1 BP S122 EP S145 DI 10.1016/j.jalz.2014.04.009 PG 24 WC Clinical Neurology SC Neurosciences & Neurology GA CP8GM UT WOS:000360130700008 PM 24924665 ER PT J AU Greenberg, MS Tanev, K Marin, MF Pitman, RK AF Greenberg, Mark S. Tanev, Kaloyan Marin, Marie-France Pitman, Roger K. TI Stress, PTSD, and dementia SO ALZHEIMERS & DEMENTIA LA English DT Article DE Stress; Dementia; Posttraumatic stress disorder; PTSD; Alzheimer's disease; Vascular dementia ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; PSYCHOLOGICAL DISTRESS; HIPPOCAMPAL ATROPHY; PSYCHIATRIC-DISORDERS; OXIDATIVE STRESS; TAU PATHOLOGY; LIFE STRESS; GREY-MATTER; BRAIN AB The physiological consequences of acute and chronic stress on a range of organ systems have been well documented after the pioneering work of Hans Selye more than 70 years ago. More recently, an association between exposure to stressful life events and the development of later-life cognitive dysfunction has been proposed. Several plausible neurohormonal pathways and genetic mechanisms exist to support such an association. However, many logistical and methodological barriers must be overcome before a defined causal linkage can be firmly established. Here the authors review recent studies of the long-term cognitive consequences of exposures to cumulative ordinary life stressors as well as extraordinary traumatic events leading to posttraumatic stress disorder. Suggestive effects have been demonstrated for the role of life stress in general, and posttraumatic stress disorder in particular, on a range of negative cognitive outcomes, including worse than normal changes with aging, Alzheimer's disease, and vascular dementia. However, given the magnitude of the issue, well-controlled studies are relatively few in number, and the effects they have revealed are modest in size. Moreover, the effects have typically only been demonstrated on a selective subset of measures and outcomes. Potentially confounding factors abound and complicate causal relationships despite efforts to contain them. More well-controlled, carefully executed longitudinal studies are needed to confirm the apparent association between stress and dementia, clarify causal relationships, develop reliable antemortem markers, and delineate distinct patterns of risk in subsets of individuals. (C) 2014 The Alzheimer's Association. All rights reserved. C1 [Greenberg, Mark S.; Tanev, Kaloyan; Marin, Marie-France; Pitman, Roger K.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Greenberg, MS (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM mark_greenberg@hms.harvard.edu FU United States Army Medical Research and Materiel Command FX Publication of this article was supported by the United States Army Medical Research and Materiel Command. NR 77 TC 12 Z9 12 U1 5 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2014 VL 10 IS 3 SU 1 BP S155 EP S165 DI 10.1016/j.jalz.2014.04.008 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CP8GM UT WOS:000360130700010 PM 24924667 ER PT J AU McKee, AC Robinson, ME AF McKee, Ann C. Robinson, Meghan E. TI Military-related traumatic brain injury and neurodegeneration SO ALZHEIMERS & DEMENTIA LA English DT Article DE Chronic traumatic encephalopathy; Veterans; Neurodegeneration; Traumatic brain injury; Tauopathy; TDP-43; Alzheimer's disease ID POSTTRAUMATIC-STRESS-DISORDER; FOOTBALL-LEAGUE PLAYER; HEAD-INJURY; ALZHEIMERS-DISEASE; WHITE-MATTER; CEREBRAL VASOSPASM; EXPLOSIVE BLAST; AXONAL INJURY; WAR VETERANS; ENCEPHALOPATHY AB Mild traumatic brain injury (mTBI) includes concussion, subconcussion, and most exposures to explosive blast from improvised explosive devices. mTBI is the most common traumatic brain injury affecting military personnel; however, it is the most difficult to diagnose and the least well understood. It is also recognized that some mTBIs have persistent, and sometimes progressive, long-term debilitating effects. Increasing evidence suggests that a single traumatic brain injury can produce long-term gray and white matter atrophy, precipitate or accelerate age-related neurodegeneration, and increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease. In addition, repetitive mTBIs can provoke the development of a tauopathy, chronic traumatic encephalopathy. We found early changes of chronic traumatic encephalopathy in four young veterans of the Iraq and Afghanistan conflict who were exposed to explosive blast and in another young veteran who was repetitively concussed. Four of the five veterans with early-stage chronic traumatic encephalopathy were also diagnosed with posttraumatic stress disorder. Advanced chronic traumatic encephalopathy has been found in veterans who experienced repetitive neurotrauma while in service and in others who were accomplished athletes. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus; septal abnormalities; and abnormal deposits of hyperphosphorylated tau as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy has clinical and pathological features that overlap with postconcussion syndrome and posttraumatic stress disorder, suggesting that the three disorders might share some biological underpinnings. (C) 2014 Published by Elsevier Inc. on behalf of The Alzheimer's Association. C1 [McKee, Ann C.; Robinson, Meghan E.] VA Boston Healthcare Syst, Boston, MA 02114 USA. [McKee, Ann C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [McKee, Ann C.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [McKee, Ann C.] Boston Univ, Sch Med, Alzheimer Dis Ctr, Boston, MA 02118 USA. RP McKee, AC (reprint author), VA Boston Healthcare Syst, Boston, MA 02114 USA. EM amckee@bu.edu RI Meijer, Anna/K-5118-2016 FU Department of Veterans Affairs; Veterans Affairs Biorepository [CSP 501]; Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C]; National Institute of Neurological Disorders and Stroke; National Institute of Biomedical Imaging and Bioengineering [UO1NS086659-01]; National Institute of Aging Boston University Alzheimer's Disease Center [P30AG13846, 0572063345-5]; Sports Legacy Institute; National Operating Committee on Standards for Athletic Equipment FX The authors gratefully acknowledge the use of resources and facilities at the Boston VA Healthcare System (Boston, MA) and Edith Nourse Rogers Memorial Veterans Hospital (Bedford, MA), as well as all of the individuals whose participation and contributions made this work possible. This work was supported by the Department of Veterans Affairs; Veterans Affairs Biorepository (CSP 501); the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C); the National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering UO1NS086659-01), National Institute of Aging Boston University Alzheimer's Disease Center [P30AG13846; supplement 0572063345-5]; the Sports Legacy Institute; and the National Operating Committee on Standards for Athletic Equipment. This work was also supported by unrestricted gifts from the National Football League, the Andlinger Foundation, and the WWE. NR 75 TC 41 Z9 41 U1 6 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2014 VL 10 IS 3 SU 1 BP S242 EP S253 DI 10.1016/j.jalz.2014.04.003 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA CP8GM UT WOS:000360130700018 PM 24924675 ER PT J AU Meziab, O Kirby, KA Williams, B Yaffe, K Byers, AL Barnes, DE AF Meziab, Omar Kirby, Katharine A. Williams, Brie Yaffe, Kristine Byers, Amy L. Barnes, Deborah E. TI Prisoner of war status, posttraumatic stress disorder, and dementia in older veterans SO ALZHEIMERS & DEMENTIA LA English DT Article DE Dementia; Risk factors; Veterans; Aged; POW; Posttraumatic stress disorder ID FOLLOW-UP; PLASMA-CORTISOL; HUMAN-MEMORY; FAR-EAST; RISK; DISABILITY; DISEASE; HEALTH; MALNUTRITION; PREVALENCE AB Background: It is not known whether prisoners of war (POWs) are more likely to develop dementia independently of the effects of posttraumatic stress disorder (PTSD). Methods: We performed a retrospective cohort study in 182,879 U.S. veterans age 55 years and older, and examined associations between POW status and PTSD at baseline (October 1, 2000-September 30, 2003), and incident dementia during follow-up (October 1, 2003-September 30, 2012). Results: A total of 484 veterans (0.3%) reported being POWs, of whom 150 (31.0%) also had PTSD. After adjusting for demographics, medical and psychiatric comorbidities, period of service, and the competing risk of death, the risk of dementia was increased in veterans who were POWs only (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.30-1.98) or had PTSD only (HR, 1.52; 95% CI, 1.41-1.64) and was greatest in veterans who were POWs and also had PTSD (HR, 2.24; 95% CI, 1.72-2.92). Conclusions: POW status and PTSD increase risk of dementia in an independent, additive manner in older veterans. (C) 2014 Published by Elsevier Inc. on behalf of The Alzheimer's Association. C1 [Meziab, Omar] Univ Arizona, Sch Med, Tucson, AZ USA. [Kirby, Katharine A.; Williams, Brie] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Kirby, Katharine A.; Williams, Brie; Yaffe, Kristine; Byers, Amy L.; Barnes, Deborah E.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Yaffe, Kristine; Byers, Amy L.; Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine; Barnes, Deborah E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Barnes, DE (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM Deborah.barnes@ucsf.edu FU Department of Defense/NCIRE (The Veterans Health Research Institute) [W81XWH-11-2-0189, 1610, 1614, W81XWH-12-1-0581]; National Institutes of Health [K24 AG031155] FX This study was supported by the Department of Defense/NCIRE (The Veterans Health Research Institute) (Barnes: W81XWH-11-2-0189, project 1610; Byers: W81XWH-11-2-0189, project 1614; Yaffe: W81XWH-12-1-0581) and the National Institutes of Health (Yaffe: K24 AG031155). The views expressed do not necessarily reflect those of the U.S. government. NR 40 TC 9 Z9 9 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2014 VL 10 IS 3 SU 1 BP S236 EP S241 DI 10.1016/j.jalz.2014.04.004 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CP8GM UT WOS:000360130700017 PM 24924674 ER PT J AU Tanner, CM Goldman, SM Ross, GW Grate, SJ AF Tanner, Caroline M. Goldman, Samuel M. Ross, G. Webster Grate, Stephen J. TI The disease intersection of susceptibility and exposure: Chemical exposures and neurodegenerative disease risk SO ALZHEIMERS & DEMENTIA LA English DT Article DE Neurodegeneration; Parkinson's disease; Alzheimer's disease; Motor neuron disease; Military; Risk factors; Pesticides; Traumatic brain injury; Solvents; Gene-environment interaction ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON-DISEASE; METHYLAMINO-L-ALANINE; GULF-WAR VETERANS; STRIATAL DOPAMINE TRANSPORTER; CUMULATIVE LEAD-EXPOSURE; PERIOD-COHORT ANALYSIS; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; POLYCHLORINATED-BIPHENYLS AB Alzheimer's disease, Parkinson's disease, and motor neuron disease, the most common of the late-life neurodegenerative disorders, are in most cases thought to have complex etiologies. Common features among these disorders include insidious onset, pathological findings of protein aggregates and selected neuronal degeneration, and resulting characteristic clinical syndromes. The number of elders in the United States, including aging veterans, is increasing. Investigation of causes and preventive interventions for neurodegenerative disorders is increasingly relevant. Recent epidemiological and laboratory studies suggest that exposures years or decades before diagnosis can trigger the processes that ultimately result in a neurodegenerative disease. If this is correct, preventive measures may be needed in midlife or earlier. This article will focus on putative risk factors relevant to military service. Published by Elsevier Inc. on behalf of The Alzheimer's Association. C1 [Tanner, Caroline M.; Goldman, Samuel M.] San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA 94121 USA. [Tanner, Caroline M.; Goldman, Samuel M.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Tanner, Caroline M.; Goldman, Samuel M.] Parkinsons Inst, Sunnyvale, CA USA. [Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA. [Grate, Stephen J.] MSAMRMC, Telemed & Adv Technol Res Ctr, Ft Detrick, MD USA. RP Tanner, CM (reprint author), San Francisco VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA 94121 USA. EM caroline.tanner@ucsf.edu FU United States Army Medical Research and Materiel Command FX Publication of this article was supported by the United States Army Medical Research and Materiel Command. NR 176 TC 14 Z9 14 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2014 VL 10 IS 3 SU 1 BP S213 EP S225 DI 10.1016/j.jalz.2014.04.014 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA CP8GM UT WOS:000360130700015 PM 24924672 ER PT J AU Yaffe, K Hoang, TD Byers, AL Barnes, DE Friedl, KE AF Yaffe, Kristine Hoang, Tina D. Byers, Amy L. Barnes, Deborah E. Friedl, Karl E. TI Lifestyle and health-related risk factors and risk of cognitive aging among older veterans SO ALZHEIMERS & DEMENTIA LA English DT Article DE Veterans; Dementia; Cognitive aging; Lifestyle behaviors; Health-related risk factors ID POSTTRAUMATIC-STRESS-DISORDER; OBSTRUCTIVE SLEEP-APNEA; CEREBRAL WHITE-MATTER; US ARMY SOLDIERS; ALZHEIMERS-DISEASE; PHYSICAL-ACTIVITY; METABOLIC SYNDROME; BLOOD-PRESSURE; SOCIAL NETWORK; MENTAL-HEALTH AB Lifestyle and health-related factors are critical components of the risk for cognitive aging among veterans. Because dementia has a prolonged prodromal phase, understanding effects across the life course could help focus the timing and duration of prevention targets. This perspective may be especially relevant for veterans and health behaviors. Military service may promote development and maintenance of healthy lifestyle behaviors, but the period directly after active duty has ended could be an important transition stage and opportunity to address some important risk factors. Targeting multiple pathways in one intervention may maximize efficiency and benefits for veterans. A recent review of modifiable risk factors for Alzheimer's disease estimated that a 25% reduction of a combination of seven modifiable risk factors including diabetes, hypertension, obesity, depression, physical inactivity, smoking, and education/cognitive inactivity could prevent up to 3 million cases worldwide and 492,000 cases in the United States. Lifestyle interventions to address cardiovascular health in veterans may serve as useful models with both physical and cognitive activity components, dietary intervention, and vascular risk factor management. Although the evidence is accumulating for lifestyle and health-related risk factors as well as military risk factors, more studies are needed to characterize these factors in veterans and to examine the potential interactions between them. Published by Elsevier Inc. on behalf of The Alzheimer's Association. C1 [Yaffe, Kristine; Byers, Amy L.; Barnes, Deborah E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine; Friedl, Karl E.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Hoang, Tina D.] Northern Calif Inst Res & Educ, San Francisco, CA USA. RP Yaffe, K (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. EM kristine.yaffe@ucsf.edu FU United States Army Medical Research and Materiel Command FX Publication of this article was supported by the United States Army Medical Research and Materiel Command. NR 160 TC 6 Z9 6 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JUN PY 2014 VL 10 IS 3 SU 1 BP S111 EP S121 DI 10.1016/j.jalz.2014.04.010 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA CP8GM UT WOS:000360130700007 PM 24924664 ER PT J AU Mannix, R Iverson, GL Maxwell, B Atkins, JE Zafonte, R Berkner, PD AF Mannix, Rebekah Iverson, Grant L. Maxwell, Bruce Atkins, Joseph E. Zafonte, Ross Berkner, Paul D. TI Multiple prior concussions are associated with symptoms in high school athletes SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article AB Objectives: The purpose of this study was to evaluate the association of prior concussion on baseline computerized neurocognitive testing in a large cohort of high school athletes. Methods: This is a retrospective cohort study of student athletes from 49 Maine High Schools in 2010 who underwent baseline computerized neurocognitive evaluation with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT (R)). As part of the ImPACT (R), subjects reported a prior history of concussion as well as demographic information and a symptom questionnaire. We used linear regression to evaluate the association of prior concussion with baseline: (1) ImPACT (R) composite scores; and (2) symptom scores. Results: Six thousand seventy-five subjects were included in the study, of whom 57% were boys. The majority of student athletes (85.3%) reported no prior history of concussion while 4.6% reported having sustained two or more prior concussions. On simple linear regression, increasing number of concussions was related to worse performance in verbal memory (P = 0.039) and greater symptoms scores (P < 0.001). On multivariate modeling, only the association with baseline symptoms remained (P < 0.001). Other factors associated with baseline symptom reporting in the multivariate model included mental health history, headache/migraine history, gender, developmental and/or learning problems, and number of prior concussions. Interpretation: In this large-scale, retrospective survey study, history of multiple prior concussions was associated with higher symptom burden but not baseline computerized neurocognitive testing. The association between baseline symptom reporting and clinical and demographic factors was greater than the association with a history of multiple concussions. C1 [Mannix, Rebekah] Boston Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. [Mannix, Rebekah; Iverson, Grant L.; Zafonte, Ross] Harvard Med Sch, Boston, MA USA. [Iverson, Grant L.; Zafonte, Ross] Harvard Med Sch, Dept Phys Med & Rehabil, Boston, MA USA. [Iverson, Grant L.; Zafonte, Ross] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.; Zafonte, Ross] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [Iverson, Grant L.; Zafonte, Ross] Spaulding Rehabil Hosp, Boston, MA USA. [Maxwell, Bruce] Colby Coll, Dept Comp Sci, Waterville, ME 04901 USA. [Atkins, Joseph E.] Colby Coll, Dept Psychol, Waterville, ME 04901 USA. [Berkner, Paul D.] Colby Coll, Hlth Serv, Waterville, ME 04901 USA. RP Mannix, R (reprint author), Boston Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. EM rebekah.mannix@childrens.harvard.edu NR 24 TC 10 Z9 10 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD JUN PY 2014 VL 1 IS 6 BP 433 EP 438 DI 10.1002/acn3.70 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V45KI UT WOS:000209815100006 PM 25356413 ER PT J AU U, KP Subramanian, V Nicholas, AP Thompson, PR Ferretti, P AF U, Kin Pong Subramanian, Venkataraman Nicholas, Antony P. Thompson, Paul R. Ferretti, Patrizia TI Modulation of calcium-induced cell death in human neural stem cells by the novel peptidylarginine deiminase-AIF pathway SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Apoptosis inducing factor (ALF); Cell death; Citrullination-deimination; Human neural stem cell; Peptidylarginine deiminase (PAD,PADI); Vimentin ID CHICK SPINAL-CORD; CITRULLINATED PROTEINS; MULTIPLE-SCLEROSIS; TRANSCRIPTIONAL REGULATION; RHEUMATOID-ARTHRITIS; NUCLEAR-LOCALIZATION; HUMAN KERATINOCYTES; CALPAIN-I; APOPTOSIS; MOUSE AB PADs (peptidylarginine deiminases) are calcium-dependent enzymes that change protein-bound arginine to citrulline (citrullination/deimination) affecting protein conformation and function. PAD up-regulation following chick spinal cord injury has been linked to extensive tissue damage and loss of regenerative capability. Having found that human neural stem cells (hNSCs) expressed PAD2 and PAD3, we studied PAD function in these cells and investigated PAD3 as a potential target for neuroprotection by mimicking calcium-induced secondary injury responses. We show that PAD3, rather than PAD2 is a modulator of cell growth/death and that PAD activity is not associated with caspase-3-dependent cell death, but is required for AIF (apoptosis inducing factor)-mediated apoptosis. PAD inhibition prevents association of PAD3 with AIF and AIF cleavage required for its translocation to the nucleus. Finally, PAD inhibition also hinders calcium-induced cytoskeleton disassembly and association of PAD3 with vimentin, that we show to be associated also with AIF; together this suggests that PAD-dependent cytoskeleton disassembly may play a role in AIF translocation to the nucleus. This is the first study highlighting a role of PAD activity in balancing hNSC survival/death, identifying PAD3 as an important upstream regulator of calciuminduced apoptosis, which could be targeted to reduce neural loss, and shedding light on the mechanisms involved. (C) 2014 The Authors. Published by Elsevier B.V. C1 [U, Kin Pong; Ferretti, Patrizia] UCL Inst Child Hlth, Dev Biol Unit, 30 Guilford St, London WC1N LEH, England. [Subramanian, Venkataraman; Thompson, Paul R.] Scripps Res Inst, Dept Chem, Scripps Florida, FL 33458 USA. [Nicholas, Antony P.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL 35294 USA. [Nicholas, Antony P.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Ferretti, P (reprint author), UCL Inst Child Hlth, Dev Biol Unit, 30 Guilford St, London WC1N LEH, England. EM p.ferretti@ucl.ac.uk OI Ferretti, Patrizia/0000-0002-3590-6772 FU Child Research Appeal Trust [08DB04]; Biotechnology and Biological Sciences Research Council; National Institutes of Health [GM079357]; Medical Research Council [G070089]; Wellcome Trust [GR082557] FX This work was supported by grants from the Child Research Appeal Trust (grant 08DB04 to PF), the Biotechnology and Biological Sciences Research Council (PF) and the National Institutes of Health (grant GM079357 to PRT). The human embryonic and fetal material was provided by the Human Developmental Biology Resource (http://lidbr.org) jointly funded by the Medical Research Council (grant G070089) and The Wellcome Trust (grant GR082557). We are grateful to J. Ham, JP Brockes and JC Sowden for reading the manuscript. The authors declare no competing financial interests. NR 68 TC 10 Z9 10 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 EI 0006-3002 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUN PY 2014 VL 1843 IS 6 BP 1162 EP 1171 DI 10.1016/j.bbamcr.2014.02.018 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AG7VW UT WOS:000335627900011 PM 24607566 ER PT J AU Palaganas, JC AF Palaganas, Janice C. TI "This is not a Simulation''-A Necessary Phrase SO CLINICAL SIMULATION IN NURSING LA English DT Editorial Material C1 [Palaganas, Janice C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Med Simulat, Boston, MA USA. RP Palaganas, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Med Simulat, Boston, MA USA. EM jpalaganas@mgh.harvard.edu NR 0 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 1876-1399 EI 1876-1402 J9 CLIN SIMUL NURS JI Clin. Simul. Nurs. PD JUN PY 2014 VL 10 IS 6 BP E283 EP E283 DI 10.1016/j.ecns.2014.04.001 PG 1 WC Nursing SC Nursing GA V42OY UT WOS:000209624300001 ER PT J AU Hofmann, SG Hinton, DE AF Hofmann, Stefan G. Hinton, Devon E. TI Cross-Cultural Aspects of Anxiety Disorders SO CURRENT PSYCHIATRY REPORTS LA English DT Review DE Culture; Anxiety disorders; DSM-5; Cross culture; Taijin kyofusho; Ataques de nervios ID LIFETIME PREVALENCE; SELF AB A person's cultural background influences the experience and expression of emotions. In reviewing the recent literature on cross-cultural aspects of anxiety disorders, we identified some culturally related ethnopsychology/ethnophysiology factors (the culture's conceptualizations of how the mind and body function) and contextual factors that influence anxiety disorders. Ethnopsychology/ethnophysiology factors include the person's ideas about the mental and bodily processes (and their interaction), whereas contextual factors are associated with the social norms and rules that may contribute to anxiety, including individualism vs. collectivism and self-construals. From the perspective of ethnopsychology/ethnophysiology and contextual factors, we will discuss "khyal cap" ("wind attacks"), taijin kyofusho, and ataques de nervios, three prominent examples of culture-specific expressions of anxiety disorders that have all been included in the DSM-5 list of cultural concepts of distress. C1 [Hofmann, Stefan G.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Hinton, Devon E.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hofmann, SG (reprint author), Boston Univ, Dept Psychol, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM shofmann@bu.edu RI Hofmann, Stefan/B-8769-2014 OI Hofmann, Stefan/0000-0002-3548-9681 FU NIH [R-1AT007257] FX Dr. Hofmann's work is supported by NIH grant R-1AT007257. NR 15 TC 6 Z9 6 U1 3 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3812 EI 1535-1645 J9 CURR PSYCHIAT REP JI Curr. Psychiatry Rep. PD JUN PY 2014 VL 16 IS 6 AR 450 DI 10.1007/s11920-014-0450-3 PG 5 WC Psychiatry SC Psychiatry GA CY1QK UT WOS:000366182300002 PM 24744049 ER PT J AU Ahern, T Khattak, A Reece, R Kilbane, M Smith, TP Lehane, C McKenna, MJ O'Shea, D Hayes, FJ AF Ahern, Tomas Khattak, Aftab Reece, Roland Kilbane, Mark Smith, Thomas P. Lehane, Ciannait McKenna, Malachi J. O'Shea, Donal Hayes, Frances J. TI Contrasting Effects of Aromatase Inhibition and Testosterone Therapy in Men with Severe Obesity: A Randomised Clinical Trial SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Ahern, Tomas; Khattak, Aftab; Reece, Roland; Kilbane, Mark; Smith, Thomas P.; Lehane, Ciannait; McKenna, Malachi J.; O'Shea, Donal] St Vincents Univ Hosp, Dublin 4, Ireland. [Hayes, Frances J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0013 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104165 ER PT J AU Babwah, AV Calder, MD Chan, YM Raj, R Elbert, A Noonan, M Caligioni, C Berube, N Bhattacharya, M Seminara, SB AF Babwah, Andy Videsh Calder, Michele Dawn Chan, Yee-Ming Raj, Renju Elbert, Adrienne Noonan, Michelle Caligioni, Claudia Berube, Nathalie Bhattacharya, Moshmi Seminara, Stephanie Beth TI Implantation Failure in Female Kiss1-/- Mice Is Independent of Their Hypogonadic State and Can be Partially Rescued By Leukemia Inhibitory Factor SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Babwah, Andy Videsh; Calder, Michele Dawn; Elbert, Adrienne; Noonan, Michelle; Berube, Nathalie; Bhattacharya, Moshmi] Univ Western Ontario, London, ON, Canada. [Chan, Yee-Ming] Massachusetts Gen Hosp, Quincy, MA USA. [Raj, Renju] Univ Vermont, Coll Med, Burlington, VT 05405 USA. [Caligioni, Claudia; Seminara, Stephanie Beth] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA LB-OR01-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107228 ER PT J AU Bachmann, KN Fazeli, PK Lawson, EA Russell, BM Riccio, AD Meenaghan, E Gerweck, AV Bredella, MA Klibanski, A Miller, KK AF Bachmann, Katherine Neubecker Fazeli, Pouneh K. Lawson, Elizabeth A. Russell, Brian M. Riccio, Ariana D. Meenaghan, Erinne Gerweck, Anu V. Bredella, Miriam A. Klibanski, Anne Miller, Karen K. TI Comparison of Hip Geometry, Strength, and Estimated Fracture Risk in Women with Anorexia Nervosa and Overweight/Obese Women SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Bachmann, Katherine Neubecker; Lawson, Elizabeth A.; Meenaghan, Erinne; Bredella, Miriam A.; Klibanski, Anne; Miller, Karen K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Fazeli, Pouneh K.] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA. [Russell, Brian M.; Riccio, Ariana D.; Gerweck, Anu V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0255 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105252 ER PT J AU Baudrand, R Wiinberg, L Adler, GK Barletta, J Chan, J Choueiri, T Dluhy, RG Elfiky, A Hamnvik, OPR Kulke, M Rainville, I Rana, HQ Ruan, DT Saxena, A Seely, EW Shyn, P Steele, AE Williams, GH Vaidya, A AF Baudrand, Rene Wiinberg, Linda Adler, Gail Kurr Barletta, Justine Chan, Jennifer Choueiri, Toni Dluhy, Robert G. Elfiky, Aymen Hamnvik, Ole-Petter Riksfjord Kulke, Matthew Rainville, Irene Rana, Huma Q. Ruan, Daniel T. Saxena, Aditi Seely, Ellen W. Shyn, Paul Steele, Amy E. Williams, Gordon H. Vaidya, Anand TI Evaluation of Quality of Life and Well-Being of Patients with Adrenal Disorders in the Setting of an Integrated Multi-Disciplinary Care Model SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Baudrand, Rene] Pontificia Univ Catolica Chile, Santiago, Chile. [Wiinberg, Linda; Adler, Gail Kurr; Barletta, Justine; Dluhy, Robert G.; Ruan, Daniel T.; Shyn, Paul; Steele, Amy E.; Williams, Gordon H.; Vaidya, Anand] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Chan, Jennifer; Choueiri, Toni; Kulke, Matthew; Rainville, Irene; Rana, Huma Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hamnvik, Ole-Petter Riksfjord; Saxena, Aditi; Seely, Ellen W.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0779 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103150 ER PT J AU Bauman, WA Swonger, KN Rivera, DR LaFountaine, MF AF Bauman, William A. Swonger, Kirsten N. Rivera, Dwindally Rosado LaFountaine, Michael F. TI HOMA beta-Cell Function Negatively Correlates to the Vasodilatory Response of Insulin in the Cutaneous Microvasculature SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Bauman, William A.; Swonger, Kirsten N.; Rivera, Dwindally Rosado] James J Peters VA Med Ctr, Bronx, NY USA. [LaFountaine, Michael F.] Seton Hall Univ, S Orange, NJ 07079 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-1029 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107120 ER PT J AU Bolo, NR Hager, B Musen, G Jacobson, AM Keshavan, M Simonson, DC AF Bolo, Nicolas R. Hager, Brandon Musen, Gail Jacobson, Alan M. Keshavan, Matcheri Simonson, Donald C. TI Hyperglycemia Disrupts Regional Brain Functional Connectivity and Increases Glutamate Neurotransmitter Levels in Type 1 Diabetes: A Link to the Development of Depression? SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Bolo, Nicolas R.; Hager, Brandon; Keshavan, Matcheri] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Musen, Gail] Joslin Diabet Ctr, Boston, MA 02215 USA. [Jacobson, Alan M.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Simonson, Donald C.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR23-5 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100109 ER PT J AU Bowlin, SJ Sadowski, T Vokes, TJ Bilezikian, JP Clarke, BL Mannstadt, M Shoback, DM Lagast, H AF Bowlin, Steven J. Sadowski, Tara Vokes, Tamara J. Bilezikian, John P. Clarke, Bart Lyman Mannstadt, Michael Shoback, Dolores M. Lagast, Hjalmar TI Paradighm (TM): A Natural History Registry for Patients with Chronic Hypoparathyroidism SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Bowlin, Steven J.] NPS Pharma, Bedminster, NJ USA. [Sadowski, Tara; Lagast, Hjalmar] NPS Pharmaceut Inc, Bedminster, NJ USA. [Vokes, Tamara J.] Univ Chicago, Chicago, IL 60637 USA. [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Clarke, Bart Lyman] Mayo Clin Rochester, Rochester, MN USA. [Mannstadt, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mannstadt, Michael] Harvard Med Sch, Boston, MA USA. [Shoback, Dolores M.] Univ Calif San Francisco, VA Med Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0197 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105103 ER PT J AU Christensen, JD Lungu, AO Cochran, E Collins, MT Gafni, RI Reynolds, JC Gorden, P Brown, RJ AF Christensen, John D. Lungu, Andreea O. Cochran, Elaine Collins, Michael T. Gafni, Rachel I. Reynolds, James C. Gorden, Phillip Brown, Rebecca J. TI Increased Bone Mineral Content in Patients with Congenital Generalized Lipodystrophy Is Unaffected By Metreleptin Replacement Therapy SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Christensen, John D.; Cochran, Elaine; Gorden, Phillip; Brown, Rebecca J.] NIDDK, NIH, Bethesda, MD USA. [Lungu, Andreea O.] Joslin Diabet Ctr, Brookline, MA USA. [Collins, Michael T.; Gafni, Rachel I.] NIDCR, NIH, Bethesda, MD USA. [Reynolds, James C.] NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR43-6 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105097 ER PT J AU Cox, KH Oliveira, LMB Plummer, LC Balasubramanian, R Crowley, WF AF Cox, Kimberly H. Oliveira, Luciana Mattos Barros Plummer, Lacey C. Balasubramanian, Ravikumar Crowley, William F. TI Heterozygous PROKR2 Mutations in Isolated GnRH Deficiency: False Positives or Dominant Negatives? SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Cox, Kimberly H.; Oliveira, Luciana Mattos Barros; Plummer, Lacey C.; Balasubramanian, Ravikumar; Crowley, William F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0609 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101227 ER PT J AU Cunningham, GR Rosen, RC Wang, C Stephens, A Ellenberg, S Matsumoto, AM Bhasin, S Molitch, ME Farrar, JT Cella, D Gill, TM Barrett-Connor, EL Cauley, JA Cifelli, D Crandall, JP Ensrud, KE Fluharty, L Hadley, E Lewis, CE Pahor, M Resnick, SM Romashkan, S Swerdloff, RS Snyder, PJ AF Cunningham, Glenn R. Rosen, Raymond C. Wang, Christina Stephens, Alisa Ellenberg, Susan Matsumoto, Alvin M. Bhasin, Shalender Molitch, Mark E. Farrar, John T. Cella, David Gill, Thomas M. Barrett-Connor, Elizabeth Louise Cauley, Jane A. Cifelli, Denise Crandall, Jill P. Ensrud, Kristine E. Fluharty, Laura Hadley, Evan Lewis, Cora E. Pahor, Marco Resnick, Susan M. Romashkan, Sergei Swerdloff, Ronald S. Snyder, Peter J. TI Free Testosterone but Not Total Testosterone or Estradiol Is Associated with Sexual Function in Symptomatic Older Hypogonadal Men in the Sexual Function Trial of the Testosterone Trials SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Cunningham, Glenn R.] Baylor Coll Med, Houston, TX 77030 USA. [Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA. [Wang, Christina] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Wang, Christina; Swerdloff, Ronald S.] Los Angeles Biomed Res Inst, Torrance, CA USA. [Stephens, Alisa; Ellenberg, Susan; Farrar, John T.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Bhasin, Shalender] Brigham & Womens Hosp, Boston, MA 02115 USA. [Molitch, Mark E.; Cella, David] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gill, Thomas M.] Yale Sch Med, New Haven, CT USA. [Barrett-Connor, Elizabeth Louise] Univ CA San Diego, La Jolla, CA USA. [Cauley, Jane A.] Univ Pittsburgh, Pittsburgh, PA USA. [Cifelli, Denise; Fluharty, Laura] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Ensrud, Kristine E.] Univ Minnesota, Minneapolis, MN USA. [Hadley, Evan; Romashkan, Sergei] NIA, Bethesda, MD 20892 USA. [Lewis, Cora E.] Univ Alabama Birmingham, Birmingham, AL USA. [Pahor, Marco] Univ Florida, Gainesville, FL USA. [Resnick, Susan M.] NIA, Baltimore, MD 21224 USA. [Swerdloff, Ronald S.] Harbor Univ Calif Med Ctr, Torrance, CA USA. [Snyder, Peter J.] Univ PA, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0084 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107199 ER PT J AU da Silva, PPB Bhatnagar, S Herman, S Zafonte, R Klibanski, A Miller, KK Tritos, NA AF da Silva, Paula Paes Batista Bhatnagar, Saurabha Herman, Seth Zafonte, Ross Klibanski, Anne Miller, Karen K. Tritos, Nicholas A. TI Predictors of Pituitary Hormone Deficiencies in Adults with History of Traumatic Brain Injury SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [da Silva, Paula Paes Batista; Klibanski, Anne; Miller, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [da Silva, Paula Paes Batista] Harvard Med Sch, Boston, MA USA. [Bhatnagar, Saurabha; Herman, Seth; Zafonte, Ross] Harvard Med Sch, Massachusetts Gen Hosp, Spaulding Rehabil Hosp, Boston, MA USA. [Tritos, Nicholas A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0732 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102096 ER PT J AU Dankel, SN Ramirez, A Xue, RD Lee, KYS Thomou, T Kasif, S Tseng, YH Kahn, CR AF Dankel, Simon Nitter Ramirez, Alfred Xue, Ruidan Lee, Kevin Yu-sun Thomou, Thomas Kasif, Simon Tseng, Yu-Hua Kahn, C. Ronald TI Preadipocyte and Adipocyte Heterogeneity within a Single White Fat Depot in Humans SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Dankel, Simon Nitter; Ramirez, Alfred; Xue, Ruidan; Lee, Kevin Yu-sun; Thomou, Thomas; Tseng, Yu-Hua] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA. [Kasif, Simon] Boston Univ, Boston, MA 02215 USA. [Kahn, C. Ronald] Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Kahn, C. Ronald] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kahn, C. Ronald] Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR46-2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103191 ER PT J AU Delaney, A Lalonde, FM Blumenthal, JD Clasen, LS Hicks, RL Denker, AH Giedd, JN Crowley, WF Balasubramanian, R AF Delaney, Angela Lalonde, Francois M. Blumenthal, Jonathan D. Clasen, Liv S. Hicks, Rebecca L. Denker, Alexander H. Giedd, Jay N. Crowley, William F. Balasubramanian, Ravikumar TI Delayed Sex Hormone Exposure during Puberty Is Associated with Differences in Brain Cortical Thickness, Spatial Ability, and Recognition Memory SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Delaney, Angela; Lalonde, Francois M.; Blumenthal, Jonathan D.; Clasen, Liv S.; Hicks, Rebecca L.; Denker, Alexander H.; Giedd, Jay N.] NIH, Bethesda, MD 20892 USA. [Crowley, William F.; Balasubramanian, Ravikumar] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR11-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104109 ER PT J AU Dichtel, LE Yuen, KCJ Bredella, MA Gerweck, AV Russell, BM Riccio, AD Gurel, MH Legg, SE Sluss, PM Biller, BMK Miller, KK AF Dichtel, Laura E. Yuen, Kevin C. J. Bredella, Miriam A. Gerweck, Anu V. Russell, Brian M. Riccio, Ariana D. Gurel, Michelle H. Legg, Stacy E. Sluss, Patrick M. Biller, Beverly M. K. Miller, Karen K. TI Overweight/Obese Adults with Pituitary Disorders Require Lower Peak Growth Hormone (GH) Cut-off Values on Glucagon Stimulation Testing (GST) to Avoid Overdiagnosis of Growth Hormone Deficiency (GHD) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Dichtel, Laura E.; Bredella, Miriam A.; Biller, Beverly M. K.; Miller, Karen K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Yuen, Kevin C. J.; Legg, Stacy E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gerweck, Anu V.; Russell, Brian M.; Riccio, Ariana D.; Gurel, Michelle H.; Sluss, Patrick M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0676 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101168 ER PT J AU Dichtel, LE Yuen, KCJ Bredella, MA Gerweck, AV Russell, BM Riccio, AD Gurel, MH Legg, SE Sluss, PM Biller, BMK Miller, KK AF Dichtel, Laura E. Yuen, Kevin C. J. Bredella, Miriam A. Gerweck, Anu V. Russell, Brian M. Riccio, Ariana D. Gurel, Michelle H. Legg, Stacy E. Sluss, Patrick M. Biller, Beverly M. K. Miller, Karen K. TI Overweight/Obese Adults with Pituitary Disorders Require Lower Peak Growth Hormone (GH) Cut-off Values on Glucagon Stimulation Testing (GST) to Avoid Overdiagnosis of Growth Hormone Deficiency (GHD) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Dichtel, Laura E.; Bredella, Miriam A.; Biller, Beverly M. K.; Miller, Karen K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Yuen, Kevin C. J.; Legg, Stacy E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gerweck, Anu V.; Russell, Brian M.; Riccio, Ariana D.; Gurel, Michelle H.; Sluss, Patrick M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP03-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109323 ER PT J AU Dichtel, LE Yuen, KCJ Bredella, MA Gerweck, AV Russell, BM Riccio, AD Gurel, MH Legg, SE Sluss, PM Biller, BMK Miller, KK AF Dichtel, Laura E. Yuen, Kevin C. J. Bredella, Miriam A. Gerweck, Anu V. Russell, Brian M. Riccio, Ariana D. Gurel, Michelle H. Legg, Stacy E. Sluss, Patrick M. Biller, Beverly M. K. Miller, Karen K. TI Overweight/Obese Adults with Pituitary Disorders Require Lower Peak Growth Hormone (GH) Cut-off Values on Glucagon Stimulation Testing (GST) to Avoid Overdiagnosis of Growth Hormone Deficiency (GHD) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Dichtel, Laura E.; Bredella, Miriam A.; Biller, Beverly M. K.; Miller, Karen K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Yuen, Kevin C. J.; Legg, Stacy E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Gerweck, Anu V.; Russell, Brian M.; Riccio, Ariana D.; Gurel, Michelle H.; Sluss, Patrick M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP03-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109324 ER PT J AU Ding, SA Simonson, DC Halperin, F Wewalka, M Foster, K Kelly, K Panosian, J Goebel-Fabbri, A Hamdy, O Clancy, K Lautz, D Vernon, A Goldfine, AB AF Ding, Su Ann Simonson, Donald C. Halperin, Florencia Wewalka, Marlene Foster, Kathleen Kelly, Katherine Panosian, Jennifer Goebel-Fabbri, Ann Hamdy, Osama Clancy, Kerni Lautz, David Vernon, Ashley Goldfine, Allison B. TI Comparative Effectiveness for Cardiometabolic Outcomes of Roux-En-Y Gastric Bypass with Intensive Diabetes and Weight Management in Obese Type 2 Diabetes SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Ding, Su Ann; Wewalka, Marlene; Foster, Kathleen; Kelly, Katherine; Panosian, Jennifer; Goebel-Fabbri, Ann; Hamdy, Osama; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Simonson, Donald C.; Halperin, Florencia; Vernon, Ashley] Brigham & Womens Hosp, Boston, MA 02115 USA. [Clancy, Kerni; Lautz, David] Emerson Hosp, Concord, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR40-2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100124 ER PT J AU Faje, AT Sullivan, R Lawrence, D Tritos, NA Klibanski, A Nachtigall, LB AF Faje, Alexander Terence Sullivan, Ryan Lawrence, Donald Tritos, Nicholas A. Klibanski, Anne Nachtigall, Lisa B. TI Ipilimumab-Induced Hypophysitis: A Detailed Longitudinal Analysis in a Large Cohort of Patients with Metastatic Melanoma SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Faje, Alexander Terence] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA. [Sullivan, Ryan; Lawrence, Donald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tritos, Nicholas A.; Klibanski, Anne; Nachtigall, Lisa B.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0674 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102009 ER PT J AU Fazeli, PK Faje, AT Cross, E Rosen, CJ Bouxsein, ML Klibanski, A AF Fazeli, Pouneh K. Faje, Alexander Terence Cross, Ela Rosen, Clifford J. Bouxsein, Mary Larsen Klibanski, Anne TI FGF-21 Is Associated with Worsened Bone Microarchitecture and Decreased Bone Strength in Anorexia Nervosa SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Fazeli, Pouneh K.; Faje, Alexander Terence] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA. [Cross, Ela; Klibanski, Anne] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME USA. [Bouxsein, Mary Larsen] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0229 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105200 ER PT J AU Garcia-Caceres, C Kim, JG Gao, YQ Wang, H Fuente-Martin, E Legutko, B Meyer, C Pfluger, PT Kahn, CR Magnan, C Luquet, S Eckel, RH Vaccarino, FM Shanabrough, M Yi, CX Horvath, TL Tschop, MH AF Garcia-Caceres, Cristina Kim, Jae Geun Gao, Yuanqing Wang, Hong Fuente-Martin, Esther Legutko, Beata Meyer, Carola Pfluger, Paul T. Kahn, C. Ronald Magnan, Christophe Luquet, Serge Eckel, Robert H. Vaccarino, Flora M. Shanabrough, Marya Yi, Chun-Xia Horvath, Tamas L. Tschoep, Matthias H. TI Astrocytes Co-Regulate Systemic Metabolism in Response to Hormones and Nutrients SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Garcia-Caceres, Cristina; Gao, Yuanqing; Fuente-Martin, Esther; Legutko, Beata; Meyer, Carola; Pfluger, Paul T.; Yi, Chun-Xia; Tschoep, Matthias H.] Tech Univ Munich, Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr, Munich, Germany. [Garcia-Caceres, Cristina; Gao, Yuanqing; Fuente-Martin, Esther; Legutko, Beata; Meyer, Carola; Pfluger, Paul T.; Yi, Chun-Xia; Tschoep, Matthias H.] Tech Univ Munich, Div Metab Dis, Munich, Germany. [Kim, Jae Geun; Shanabrough, Marya; Horvath, Tamas L.] Yale Univ, Sch Med, Comparat Med Sect, Program Integrat Cell Signaling & Neurobiol Metab, New Haven, CT 06520 USA. [Wang, Hong; Eckel, Robert H.] Univ Colorado, Dept Internal Med, Div Metab Endocrinol & Diabet, Aurora, CO USA. [Kahn, C. Ronald] Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA. [Kahn, C. Ronald] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kahn, C. Ronald] Harvard Med Sch, Boston, MA 02115 USA. [Magnan, Christophe; Luquet, Serge] Univ Paris Diderot Paris 7, CNRS, EAC 4413, Unite Biol Fonct & Adaptat, F-75205 Paris 13, France. [Vaccarino, Flora M.] Yale Univ, Dept Neurobiol, Child Study Ctr, New Haven, CT 06520 USA. [Vaccarino, Flora M.] Yale Univ, Kavli Inst Neurosci, New Haven, CT 06520 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR45-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103148 ER PT J AU Grimes, MC Mathew, I Bandi, A Martin, E Codario, R Rao, RH AF Grimes, Michael C. Mathew, Indu Bandi, Archana Martin, Emily Codario, Ronald Rao, R. Harsha TI Impact of U-500 Insulin on Glycemic Control, Risk of Hypoglycemia, and Mortality in Patients with Extreme Insulin Resistance: The VA Pittsburgh Experience SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Grimes, Michael C.; Mathew, Indu] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Bandi, Archana] VAPHS Oakland, Wexford, PA USA. [Martin, Emily] VA Pittsburgh Healthcare Syst, Munhall, PA USA. [Codario, Ronald] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Rao, R. Harsha] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR54-6 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100135 ER PT J AU Hattersley, G Dean, T Gardella, TJ AF Hattersley, Gary Dean, Thomas Gardella, Thomas James TI Differential Binding Selectivity of Abaloparatide (BA058) Compared to PTH and PTHrP for PTH Type 1 Receptor Conformations SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Hattersley, Gary] Radius Hlth Inc, Cambridge, MA USA. [Dean, Thomas; Gardella, Thomas James] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR31-5 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105215 ER PT J AU Hershman, JM Liwanpo, L Ro, C ul Haq, MS AF Hershman, Jerome M. Liwanpo, Llanyee Ro, Cynthia ul Haq, Muhammd Salman TI Sunitinib Does Not Inhibit Thyroid Peroxidase in Patients SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Hershman, Jerome M.] VA Greater LA Healthcare Syst, Los Angeles, CA USA. [Liwanpo, Llanyee; Ro, Cynthia] VA Greater Los Angeles, Los Angeles, CA USA. [ul Haq, Muhammd Salman] Sansum Clin, Santa Barbara, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0507 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109004 ER PT J AU Huynh, J Lee, H Clish, CB Nathan, DM Thadhani, R Gerszten, RE Bentley-Lewis, R AF Huynh, Jennifer Lee, Hang Clish, Clary B. Nathan, David M. Thadhani, Ravi Gerszten, Robert E. Bentley-Lewis, Rhonda TI Metabolomic Profiling in the Prediction of Gestational Diabetes Mellitus SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Huynh, Jennifer; Lee, Hang; Nathan, David M.; Thadhani, Ravi; Gerszten, Robert E.; Bentley-Lewis, Rhonda] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clish, Clary B.] Broad Inst MIT & Harvard, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR20-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100028 ER PT J AU Iacovazzo, D Morrison, PJ Foulkes, W Ross, DS Lugli, F Gabrovska, P Lucci-Cordisco, E De Marinis, L Korbonits, M AF Iacovazzo, Donato Morrison, Patrick J. Foulkes, William Ross, Douglas S. Lugli, Francesca Gabrovska, Plamena Lucci-Cordisco, Emanuela De Marinis, Laura Korbonits, Marta TI Four Families with RET-Mutation Negative Familial Medullary Thyroid Carcinoma: What Lies Beyond RET? SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Iacovazzo, Donato; Gabrovska, Plamena] Queen Mary Univ London, William Harvey Res Inst, London, England. [Morrison, Patrick J.] Belfast City Hosp, Belfast, Antrim, North Ireland. [Foulkes, William] McGill Univ, Montreal, PQ, Canada. [Ross, Douglas S.] Mass Gen Hosp, Boston, MA USA. [Lugli, Francesca; Lucci-Cordisco, Emanuela; De Marinis, Laura] Catholic Univ, Rome, Italy. [Korbonits, Marta] Queen Mary Univ London, Bails & London Sch Med, William Harvey Res Inst, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0546 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109226 ER PT J AU Iacovazzo, D Morrison, PJ Foulkes, W Ross, DS Lugli, F Gabrovska, P Lucci-Cordisco, E De Marinis, L Korbonits, M AF Iacovazzo, Donato Morrison, Patrick J. Foulkes, William Ross, Douglas S. Lugli, Francesca Gabrovska, Plamena Lucci-Cordisco, Emanuela De Marinis, Laura Korbonits, Marta TI Four Families with RET-Mutation Negative Familial Medullary Thyroid Carcinoma: What Lies Beyond RET? SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Iacovazzo, Donato; Gabrovska, Plamena] Queen Mary Univ London, William Harvey Res Inst, London, England. [Morrison, Patrick J.] Belfast City Hosp, Belfast, Antrim, North Ireland. [Foulkes, William] McGill Univ, Montreal, PQ, Canada. [Ross, Douglas S.] Mass Gen Hosp, Boston, MA USA. [Lugli, Francesca; Lucci-Cordisco, Emanuela; De Marinis, Laura] Catholic Univ, Rome, Italy. [Korbonits, Marta] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP39-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109148 ER PT J AU Jain, R Izquierdo, RE McGrath, M Rosenbaum, P AF Jain, Rohit Izquierdo, Roberto Emilio McGrath, Mary Rosenbaum, Paula TI Poor RAI Treatment Outcomes in Persistent/Recurrent Follicular Cell- Derived Thyroid Cancer with Negative Diagnostic Whole Body Scans (DxWBS) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Jain, Rohit; McGrath, Mary; Rosenbaum, Paula] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. [Izquierdo, Roberto Emilio] Joslin Diabet Ctr, Syracuse, NY USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0577 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109218 ER PT J AU Jensen, T Wang, CCL AF Jensen, Thomas Wang, Cecilia C. Low TI Double Trouble: A Case of Primary Hyperparathyroidism and Humoral Hypercalcemia of Malignancy SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Jensen, Thomas] Univ Colorado, Sch Med, Aurora, CO USA. [Wang, Cecilia C. Low] Denver VAMC, Denver, CO USA. [Wang, Cecilia C. Low] Univ Colorado Sh, Denver, CO USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0202 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105128 ER PT J AU Kievit, P Pound, L Hobbs, T Martin, D Johnson, C Escalona, A Bader, L Valleau, J Elmquist, JK Seeley, R Kaplan, L Grove, KL AF Kievit, Paul Pound, Lynley Hobbs, Theodore Martin, Drew Johnson, Chris Escalona, Alex Bader, Lindsay Valleau, Jeanette Elmquist, Joel Keith Seeley, Randy Kaplan, Lee Grove, Kevin L. TI Caloric Intake Reduction Following Roux-En-Y Gastric Bypass Surgery Drives Rapid Improvements in Glucose Homeostasis and Beta Cell Function in Obese Rhesus Macaques SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Kievit, Paul; Pound, Lynley; Hobbs, Theodore; Martin, Drew; Johnson, Chris; Bader, Lindsay; Valleau, Jeanette; Grove, Kevin L.] Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Escalona, Alex; Kaplan, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Elmquist, Joel Keith] UT Southwestern Med Ctr, Dallas, TX USA. [Seeley, Randy] Univ Cincinnati, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0921 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103246 ER PT J AU Kim, SC Glynn, R Liu, J Everett, BM Goldfine, AB AF Kim, Seoyoung C. Glynn, Robert Liu, Jun Everett, Brendan M. Goldfine, Allison B. TI Dipeptidyl Peptidase-4 Inhibitors Do Not Increase the Risk of Cardiovascular Events in Type 2 Diabetes: A Population-Based Cohort Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Kim, Seoyoung C.; Glynn, Robert; Liu, Jun; Everett, Brendan M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR34-6 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100082 ER PT J AU Kocarnik, BM Kahn, SE Fujimoto, WY Hayashi, T McNeely, MJ Leonetti, D Boyko, EJ AF Kocarnik, Beverly M. Kahn, Steven E. Fujimoto, Wilfred Y. Hayashi, Tomoshige McNeely, Marguerite J. Leonetti, Donna Boyko, Edward J. TI Estradiol Levels in Men Are Not Correlated Cross-Sectionally with Intra-Abdominal Fat Area and Do Not Predict Change in This Fat Depot Longitudinally SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Kocarnik, Beverly M.; Kahn, Steven E.; McNeely, Marguerite J.; Leonetti, Donna] Univ Washington, Seattle, WA 98195 USA. [Kahn, Steven E.; Boyko, Edward J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Fujimoto, Wilfred Y.] Univ Washington, Kailua Kona, HI USA. [Hayashi, Tomoshige] Osaka Univ, Osaka, Japan. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0905 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103097 ER PT J AU Lawson, EA Fazeli, PK Marengi, DA Cross, E Bouxsein, ML Miller, KK Faje, AT Klibanski, A AF Lawson, Elizabeth A. Fazeli, Pouneh K. Marengi, Dean A. Cross, Ela Bouxsein, Mary L. Miller, Karen K. Faje, Alexander Terence Klibanski, Anne TI Oxytocin Levels Are Associated with Trabecular Microarchitecture in Healthy Women, but Not in Women with Anorexia Nervosa SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Lawson, Elizabeth A.; Marengi, Dean A.; Cross, Ela; Miller, Karen K.; Klibanski, Anne] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Fazeli, Pouneh K.; Faje, Alexander Terence] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA. [Bouxsein, Mary L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0228 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105198 ER PT J AU Lawson, EA Fazeli, PK Marengi, DA Cross, E Faje, AT Rosen, CJ Breggia, AC Miller, KK Klibanski, A AF Lawson, Elizabeth A. Fazeli, Pouneh K. Marengi, Dean A. Cross, Ela Faje, Alexander Terence Rosen, Clifford J. Breggia, Anne C. Miller, Karen K. Klibanski, Anne TI Irisin Levels Are High in Anorexia Nervosa and Inversely Associated with Resting Energy Expenditure SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Lawson, Elizabeth A.; Marengi, Dean A.; Cross, Ela; Miller, Karen K.; Klibanski, Anne] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Fazeli, Pouneh K.; Faje, Alexander Terence] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA USA. [Rosen, Clifford J.] Maine Med Ctr, Res Inst, Scarborough, ME USA. [Breggia, Anne C.] Maine Med Ctr, Rsrch Inst, Scarborough, ME USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0920 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103245 ER PT J AU Li, YB Fortin, J Boehm, U Lin, HY Bernard, DJ AF Li, Yining Fortin, Jerome Boehm, Ulrich Lin, Herbert Y. Bernard, Daniel J. TI Enhanced Fertility and FSH Synthesis in Mice Lacking the Inhibin Co-Receptor TGFBR3 (betaglycan) in Pituitary Gonadotropes SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Li, Yining; Fortin, Jerome; Bernard, Daniel J.] McGill Univ, Montreal, PQ, Canada. [Boehm, Ulrich] Univ Saarland, Sch Med, Homburg, Germany. [Lin, Herbert Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lin, Herbert Y.] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0361 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100269 ER PT J AU Lippincott, MF Chan, YM Seminara, SB AF Lippincott, Margaret Flynn Chan, Yee-Ming Seminara, Stephanie Beth TI Responses to Continuous Kisspeptin-10 Infusions: Influences of Sex and Sex Steroids SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Lippincott, Margaret Flynn; Chan, Yee-Ming; Seminara, Stephanie Beth] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0640 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101261 ER PT J AU Lippincott, MF Chan, YM Seminara, SB AF Lippincott, Margaret Flynn Chan, Yee-Ming Seminara, Stephanie Beth TI Responses to Continuous Kisspeptin-10 Infusions: Influences of Sex and Sex Steroids SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Lippincott, Margaret Flynn; Chan, Yee-Ming; Seminara, Stephanie Beth] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0640 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101260 ER PT J AU Liu, XH Collier, L Ma, RS Latif, R Davies, TF Bauman, WA Cardozo, CP AF Liu, Xin-Hua Collier, Lauren Ma, Risheng Latif, Rauf Davies, Terry F. Bauman, William A. Cardozo, Christopher Pratt TI Androgens Promote Differentiation of Induced Pluripotent Stem Cells to Mesenchymal Progenitor Cells through Embryoid Body Formation SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Liu, Xin-Hua; Collier, Lauren; Bauman, William A.; Cardozo, Christopher Pratt] JJ Peter VA Med Ctr, Bronx, NY USA. [Ma, Risheng] Mt Sinai Sch Med, Bronx, NY USA. [Latif, Rauf; Davies, Terry F.] Mt Sinai Sch Med, New York, NY USA. [Bauman, William A.] James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0262 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105285 ER PT J AU Lombardi, A Inabnet, WB Owen, R Tomer, Y AF Lombardi, Angela Inabnet, William B. Owen, Randall Tomer, Yaron TI A New Mechanism for Iodine Independent Amiodarone-Induced Thyroiditis with Translational Implications SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Lombardi, Angela; Inabnet, William B.; Owen, Randall; Tomer, Yaron] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Tomer, Yaron] James J Peters VA Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR12-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109054 ER PT J AU Malhotra, S Gupta, N Galiveeti, S Milekic, B Greenberg, PD AF Malhotra, Sheetal Gupta, Namita Galiveeti, Sneha Milekic, Bojana Greenberg, Pietra Dale TI Sleeve Gastrectomy Outcomes in Veterans with Type II Diabetes SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Malhotra, Sheetal; Galiveeti, Sneha; Milekic, Bojana] JJ Peters VA Med Ctr, Bronx, NY USA. [Gupta, Namita] Univ Nebraska Med Ctr, Omaha, NE USA. [Greenberg, Pietra Dale] James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR40-4 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100127 ER PT J AU Mannstadt, M Vokes, TJ Watts, NB Denham, D Shoback, DM Clarke, BL Lagast, H Bilezikian, JP AF Mannstadt, Michael Vokes, Tamara J. Watts, Nelson B. Denham, Douglas Shoback, Dolores M. Clarke, Bart Lyman Lagast, Hjalmar Bilezikian, John P. TI Long-Term Safety and Efficacy of Recombinant Human Parathyroid Hormone (rhPTH[1-84]) for the Treatment of Adults with Hypoparathyroidism: Interim Data from the Race Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Mannstadt, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mannstadt, Michael] Harvard Med Sch, Boston, MA USA. [Vokes, Tamara J.] Univ Chicago, Chicago, IL 60637 USA. [Watts, Nelson B.] Mercy Hlth Osteoporosis Serv, Cincinnati, OH USA. [Watts, Nelson B.] Mercy Bone Hlth Serv, Cincinnati, OH USA. [Denham, Douglas] Clin Trials Texas Inc, San Antonio, TX USA. [Shoback, Dolores M.] Univ Calif San Francisco, VA Med Ctr, San Francisco, CA 94143 USA. [Clarke, Bart Lyman] Mayo Clin Rochester, Rochester, MN USA. [Lagast, Hjalmar] NPS Pharmaceut, Bedminster, NJ USA. [Bilezikian, John P.] Columbia Univ, Coll Phys & Surg, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0210 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105117 ER PT J AU Manzano, A Fernandez-Castro, GL Nose, V Ayala, A AF Manzano, Alex Fernandez-Castro, Gustavo L. Nose, Vania Ayala, Alejandro TI Recurrent Primary Adrenal Leiomyosarcoma: A Case of a Rare Adrenal Tumor SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Manzano, Alex; Fernandez-Castro, Gustavo L.; Ayala, Alejandro] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Nose, Vania] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0759 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105232 ER PT J AU Mathew, I Grimes, MC Rao, RH Cunningham, CA Muder, R Perreiah, PL AF Mathew, Indu Grimes, Michael C. Rao, R. Harsha Cunningham, Candace Ann Muder, Robert Perreiah, Peter L. TI Eliminating Deaths from Mediastinitis after Cardiac Surgery Using Aggressive Glycemic Intervention to Maintain Blood Glucose 80-140mg/DI: The VA Pittsburgh Experience SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Mathew, Indu; Grimes, Michael C.; Muder, Robert] VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. [Rao, R. Harsha; Cunningham, Candace Ann; Perreiah, Peter L.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0956 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106240 ER PT J AU Mehta, SN Niewczas, MA McMullen, WJ Gruener, AH Doria, A AF Mehta, Sanjeev N. Niewczas, Monika A. McMullen, William J. Gruener, Alf H. Doria, Alessandro TI Factors Associated with Choice of Incretin-Based Medication Class in Adults with Type 2 Diabetes (T2D) SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Mehta, Sanjeev N.; Niewczas, Monika A.; McMullen, William J.; Doria, Alessandro] Joslin Diabet Ctr, Boston, MA 02215 USA. [Gruener, Alf H.] Sanofi, Bridgewater, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-1007 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106295 ER PT J AU Min, L Hodi, FS Carroll, RS Kaiser, UB AF Min, Le Hodi, F. Stephen Carroll, Rona S. Kaiser, Ursula B. TI Hypophysitis Associated with Ipilimumab, a Novel Immunotherapy for Metastatic Melanoma: Analysis of 26 Cases SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Min, Le] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carroll, Rona S.; Kaiser, Ursula B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Carroll, Rona S.; Kaiser, Ursula B.] Harvard Med Sch, Div Endocrinol Diabet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0675 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102010 ER PT J AU Misra, M Eguiguren, MD Singhal, V Ackerman, KE Clarke, H Slattery, M Eddy, KT AF Misra, Madhusmita Eguiguren, Maria de Lourdes Singhal, Vibha Ackerman, Kathryn Elizabeth Clarke, Hannah Slattery, Meghan Eddy, Kamryn T. TI Increased Cognitive Restraint in Amenorrheic Adolescent and Young Adults Athletes Is Associated with Higher Cortisol Secretion and Trunk Fat and Lower Bone Density SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Misra, Madhusmita; Eguiguren, Maria de Lourdes; Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Eddy, Kamryn T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Misra, Madhusmita; Eguiguren, Maria de Lourdes; Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0648 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101269 ER PT J AU Mitchell, DM Jueppner, HW Burnett-Bowie, SAM AF Mitchell, Deborah Michelle Jueppner, Harald W. Burnett-Bowie, Sherri-Ann M. TI Fibroblast Growth Factor 23 Is Not Associated with Age-Related Changes in Phosphate Handling in Children SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Mitchell, Deborah Michelle; Jueppner, Harald W.; Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR43-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105094 ER PT J AU Muram, D Matsumoto, AM Zhang, X Cui, ZLL AF Muram, David Matsumoto, Alvin M. Zhang, Xiang Cui, Zhanglin Lin TI Application of the Endocrine Society Clinical Guidelines on Testosterone Therapy in Men with Androgen Deficiency Syndromes in Clinical Practice SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Muram, David; Zhang, Xiang; Cui, Zhanglin Lin] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0021 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104173 ER PT J AU O-Sullivan, I Li, K Wasserman, D Kahn, CR Schwartz, MW Unterman, TG AF O-Sullivan, InSug Li, Kang Wasserman, David Kahn, C. Ronald Schwartz, Michael W. Unterman, Terry G. TI Disruption of FoxO1 Restores the Ability of Insulin to Regulate Hepatic Glucose Production in Liver-Specific Insulin Receptor Knockout (LIRKO) Mice SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [O-Sullivan, InSug; Unterman, Terry G.] Univ Illinois, Chicago, IL USA. [O-Sullivan, InSug; Unterman, Terry G.] Jesse Brown VAMC, Chicago, IL USA. [Li, Kang; Wasserman, David] Vanderbilt Univ, Nashville, TN 37235 USA. [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. [Schwartz, Michael W.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-1042 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100008 ER PT J AU Pau, CT Kasippillai, T Keefe, C Welt, CK AF Pau, Cindy Ta Kasippillai, Thushiga Keefe, Candace Welt, Corrine K. TI Response to Metformin in Women with PCOS: The Role of Variants Regulating Metformin Transport and Action SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Pau, Cindy Ta; Keefe, Candace; Welt, Corrine K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kasippillai, Thushiga] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR47-5 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107224 ER PT J AU Pivonello, R Fleseriu, M Young, J Bertagna, X Hamrahian, AH Molitch, ME Shimizu, C Tanaka, T Shimatsu, A White, T Hilliard, A Tian, C Sauter, N Biller, BMK AF Pivonello, Rosario Fleseriu, Maria Young, Jacques Bertagna, Xavier Hamrahian, Amir H. Molitch, Mark E. Shimizu, Chikara Tanaka, Tomoaki Shimatsu, Akira White, Tracy Hilliard, Annie Tian, Chuan Sauter, Nicholas Biller, Beverly M. K. TI LCI699, a Potent 11 beta-Hydroxylase Inhibitor, Normalizes Urinary Free Cortisol Levels in Patients with Cushing's Disease: 22-Week, Multicenter, Open-Label Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Pivonello, Rosario] Univ Naples Federico II, Naples, Italy. [Fleseriu, Maria] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Young, Jacques] Univ Paris Sud, Hop Bicetre, Assistance Publ Hop Paris, Paris, France. [Bertagna, Xavier] Univ Paris 05, Hop Cochin, Fac Med Paris Descartes, Ctr Reference Malad Rares Surrenale, Paris, France. [Hamrahian, Amir H.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Molitch, Mark E.] Northwestern Univ, Chicago, IL 60611 USA. [Shimizu, Chikara] Hokkaido Univ Hosp, Sapporo, Hokkaido, Japan. [Tanaka, Tomoaki] Chiba Univ Hosp, Chiba, Japan. [Shimatsu, Akira] Natl Hosp Org, Kyoto Med Ctr, Kyoto, Japan. [White, Tracy; Hilliard, Annie; Tian, Chuan; Sauter, Nicholas] Novartis Pharmaceut, E Hanover, NJ USA. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR17-4 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101137 ER PT J AU Qin, WP Pan, JP Bauman, WA Cardozo, CP AF Qin, Weiping Pan, Jianping Bauman, William A. Cardozo, Christopher Pratt TI Molecular Crosstalk Between Calcineurin and mTORC1 Signaling Pathways SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Qin, Weiping; Pan, Jianping; Bauman, William A.; Cardozo, Christopher Pratt] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0351 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100258 ER PT J AU Rietman, A Stanley, TL Clish, CB Mootha, VK Mensink, M Grinspoon, SK Makimura, H AF Rietman, Annemarie Stanley, Takara Leah Clish, Clary B. Mootha, Vamsi K. Mensink, Marco Grinspoon, Steven Kyle Makimura, Hideo TI Novel Association Between Branched Chain Amino Acids, eta-Arninoisobutyric Acid and Abdominal Visceral Adiposity: A Metabolomics Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Rietman, Annemarie; Mensink, Marco] Wageningen Univ, Wageningen, Netherlands. [Stanley, Takara Leah; Grinspoon, Steven Kyle; Makimura, Hideo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clish, Clary B.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Mootha, Vamsi K.] Harvard Med Sc, MIT Broad last, Cambridge, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0934 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103166 ER PT J AU Russell, SJ El-Khatib, FH Magyar, KL Sinha, M Goergen, LG Balliro, C McKeon, K Nathan, DM Damiano, ER AF Russell, Steven Jon El-Khatib, Firas H. Magyar, Kendra L. Sinha, Manasi Goergen, Laura G. Balliro, Courtney McKeon, Katherine Nathan, David M. Damiano, Edward R. TI Multiday Outpatient Glycemic Control in Adults with Type 1 Diabetes Using a Bihormonal Bionic Pancreas: The Beacon Hill Study SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Russell, Steven Jon; Magyar, Kendra L.; Sinha, Manasi; Goergen, Laura G.; Balliro, Courtney; Nathan, David M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [El-Khatib, Firas H.; McKeon, Katherine; Damiano, Edward R.] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR26-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100117 ER PT J AU Shaw, ND Srouji, S Welt, CK Cox, KH Fox, JH Adamss, JM Sluss, PM Hall, JE AF Shaw, Natalie D. Srouji, Serene Welt, Corrine K. Cox, Kimberly H. Fox, Janis H. Adamss, Judith Mary Sluss, Patrick M. Hall, Janet Elizabeth TI Evidence That Ovarian Aromatase Action Is Preserved with Aging in Regularly Cycling Women SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Shaw, Natalie D.] Boston Childrens Hosp, Boston, MA USA. [Srouji, Serene; Fox, Janis H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Welt, Corrine K.; Cox, Kimberly H.; Sluss, Patrick M.; Hall, Janet Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adamss, Judith Mary] MA Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR04-6 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104222 ER PT J AU Shaw, ND Butler, JP Kangarloo, T Hall, JE AF Shaw, Natalie D. Butler, James P. Kangarloo, Tairmae Hall, Janet Elizabeth TI Deep Sleep Disruption Does Not Diminish Pulsatile LH Secretion in Pubertal Children SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Shaw, Natalie D.] Boston Childrens Hosp, Boston, MA USA. [Butler, James P.] Harvard Sch Publ Hlth, Boston, MA USA. [Kangarloo, Tairmae] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hall, Janet Elizabeth] Massachusetts Gen, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0158 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805104071 ER PT J AU Shi, Y Kim, MS Shu, ZJ Salmon, A Kamat, A AF Shi, Yun Kim, Margaret S. Shu, Zhen-Ju Salmon, Adam Kamat, Amrita TI Positive Association Between Beta(2)-Adrenergic Receptor (beta(2)-AR) Signaling and Cide Family Proteins in Hepatic Steatosis SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Shi, Yun; Kim, Margaret S.; Shu, Zhen-Ju] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Salmon, Adam; Kamat, Amrita] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR15-2 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106048 ER PT J AU Shores, MM Fox, AE Moore, KP Matsumoto, AM Forsberg, CW Smith, NL Heckbert, SR Thompson, ML Walsh, TJ AF Shores, Molly M. Fox, Alexandra E. Moore, Kathryn P. Matsumoto, Alvin M. Forsberg, Christopher W. Smith, Nicholas L. Heckbert, Susan R. Thompson, Mary Lou Walsh, Thomas J. TI Characteristics of Treated and Untreated Middle-Aged and Older Men with Low Testosterone and Testosterone Use in a National Veterans Affairs (VA) Cohort SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Shores, Molly M.] Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. [Fox, Alexandra E.] Seattle VA Epidemiol Res & Informat Ctr ERIC, Seattle, WA USA. [Moore, Kathryn P.; Forsberg, Christopher W.] Seattle VA ERIC, Seattle, WA USA. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syste, Seattle, WA USA. [Smith, Nicholas L.; Heckbert, Susan R.; Thompson, Mary Lou; Walsh, Thomas J.] Univ Washington, Seattle, WA 98195 USA. [Smith, Nicholas L.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0077 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805107192 ER PT J AU Simonson, DC Ding, SA Halperin, F Wewalka, M Foster, K Kelly, K Panosian, J Goebel-Fabbri, A Hamdy, O Clancy, K Lautz, D Vernon, A Goldfine, AB AF Simonson, Donald C. Ding, Su Ann Halperin, Florencia Wewalka, Marlene Foster, Kathleen Kelly, Katherine Panosian, Jennifer Goebel-Fabbri, Ann Hamdy, Osama Clancy, Kerni Lautz, David Vernon, Ashley Goldfine, Allison B. TI Changes in Patient-Reported Outcomes up to Two Years after Roux-En-Y Gastric Bypass Vs. Intensive Medical Weight Management in Obese Patients with Type 2 Diabetes Mellitus SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Simonson, Donald C.; Halperin, Florencia; Vernon, Ashley] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ding, Su Ann; Wewalka, Marlene; Foster, Kathleen; Kelly, Katherine; Panosian, Jennifer; Goebel-Fabbri, Ann; Hamdy, Osama; Goldfine, Allison B.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Clancy, Kerni; Lautz, David] Emerson Hosp, Concord, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR40-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100125 ER PT J AU Singhal, V Bredella, MA Ackerman, KE Clarke, H Slattery, M Misra, M AF Singhal, Vibha Bredella, Miriam A. Ackerman, Kathryn Elizabeth Clarke, Hannah Slattery, Meghan Misra, Madhusmita TI Bone Marrow Fat in Relation to Bone Density in Young Oligo-Amenorrheic Athletes and Eumenorrheic Controls SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Harvard Med Sch, Boston, MA USA. [Bredella, Miriam A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0227 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105197 ER PT J AU Singhal, V Bredella, MA Ackerman, KE Clarke, H Slattery, M Misra, M AF Singhal, Vibha Bredella, Miriam A. Ackerman, Kathryn Elizabeth Clarke, Hannah Slattery, Meghan Misra, Madhusmita TI Bone Marrow Fat in Relation to Bone Density in Young Oligo-Amenorrheic Athletes and Eumenorrheic Controls SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Harvard Med Sch, Boston, MA USA. [Bredella, Miriam A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP31-2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105044 ER PT J AU Singhal, V Ackerman, KE Clarke, H Slattery, M Weiner, L Kolodny, G Cypess, AM Misra, M AF Singhal, Vibha Ackerman, Kathryn Elizabeth Clarke, Hannah Slattery, Meghan Weiner, Lauren Kolodny, Gerald Cypess, Aaron Martin Misra, Madhusmita TI Cold Induced Brown Adipose Tissue Activity in Young Oligo-Amenorrheic Athletes SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Misra, Madhusmita] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Singhal, Vibha; Ackerman, Kathryn Elizabeth; Clarke, Hannah; Slattery, Meghan; Weiner, Lauren; Misra, Madhusmita] Harvard Med Sch, Boston, MA USA. [Weiner, Lauren; Cypess, Aaron Martin] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kolodny, Gerald] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0884 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103033 ER PT J AU Somm, E Xu, C Miraoui, H Kinnunen, T Preitner, N Dwyer, A Sykiotis, G Quinton, R Crowley, WF Hauschild, M Phan-Hug, F Sidis, Y Mohammadi, M Pitteloud, N AF Somm, Emmanuel Xu, Cheng Miraoui, Hichem Kinnunen, Tarja Preitner, Nadia Dwyer, Andrew Sykiotis, Gerasimos Quinton, Richard Crowley, William F. Hauschild, Michael Phan-Hug, Franziska Sidis, Yisrael Mohammadi, Moosa Pitteloud, Nelly TI Klb, Encoding the Co-Receptor for FGF21, Is Mutated in Congenital GnRH Deficiency SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Somm, Emmanuel; Xu, Cheng; Miraoui, Hichem; Preitner, Nadia; Dwyer, Andrew; Sykiotis, Gerasimos; Hauschild, Michael; Phan-Hug, Franziska; Sidis, Yisrael; Pitteloud, Nelly] CHU Vaudois, Lausanne, Switzerland. [Kinnunen, Tarja] Univ Huddersfield, Huddersfield, W Yorkshire, England. [Quinton, Richard] Univ Newcastle On Tyne, Newcastle Upon Tyne, Tyne & Wear, England. [Crowley, William F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mohammadi, Moosa] NYU, Sch Med, New York, NY USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0602 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101218 ER PT J AU Somm, E Xu, C Miraoui, H Kinnunen, T Preitner, N Dwyer, A Sykiotis, G Quinton, R Crowley, WF Hauschild, M Phan-Hug, F Sidis, Y Mohammadi, M Pitteloud, N AF Somm, Emmanuel Xu, Cheng Miraoui, Hichem Kinnunen, Tarja Preitner, Nadia Dwyer, Andrew Sykiotis, Gerasimos Quinton, Richard Crowley, William F. Hauschild, Michael Phan-Hug, Franziska Sidis, Yisrael Mohammadi, Moosa Pitteloud, Nelly TI Klb, Encoding the Co-Receptor for FGF21, Is Mutated in Congenital GnRH Deficiency SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Somm, Emmanuel; Xu, Cheng; Miraoui, Hichem; Preitner, Nadia; Dwyer, Andrew; Sykiotis, Gerasimos; Hauschild, Michael; Phan-Hug, Franziska; Sidis, Yisrael; Pitteloud, Nelly] CHU Vaudois, Lausanne, Switzerland. [Kinnunen, Tarja] Univ Huddersfield, Huddersfield, W Yorkshire, England. [Quinton, Richard] Univ Newcastle On Tyne, Newcastle Upon Tyne, Tyne & Wear, England. [Crowley, William F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mohammadi, Moosa] NYU, Sch Med, New York, NY USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP30-1 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101194 ER PT J AU Srinivasa, S Fitch, KV Wong, K Petrow, E Grinspoon, SK AF Srinivasa, Suman Fitch, Kathleen V. Wong, Kimberly Petrow, Eva Grinspoon, Steven Kyle TI Effects of Lifestyle Modification and Metformin on Irisin and FGF21 Among HIV-Infected Patients with the Metabolic Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Srinivasa, Suman; Fitch, Kathleen V.; Wong, Kimberly; Petrow, Eva] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grinspoon, Steven Kyle] Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP05-3 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103265 ER PT J AU Srinivasa, S Fitch, KV Wong, K Petrow, E Grinspoon, SK AF Srinivasa, Suman Fitch, Kathleen V. Wong, Kimberly Petrow, Eva Grinspoon, Steven Kyle TI Effects of Lifestyle Modification and Metformin on Irisin and FGF21 Among HIV-Infected Patients with the Metabolic Syndrome SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Srinivasa, Suman; Fitch, Kathleen V.; Wong, Kimberly; Petrow, Eva] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Grinspoon, Steven Kyle] Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0924 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103155 ER PT J AU Stanley, TL Feldpausch, MN Oh, J Branch, KL Lee, H Torriani, M Grinspoon, SK AF Stanley, Takara Leah Feldpausch, Meghan N. Oh, Jinhee Branch, Karen L. Lee, Hang Torriani, Martin Grinspoon, Steven Kyle TI Growth Hormone Releasing Hormone Analogue Reduces Liver Fat in HIV-Infected Patients SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Stanley, Takara Leah; Feldpausch, Meghan N.; Oh, Jinhee; Branch, Karen L.; Lee, Hang; Torriani, Martin; Grinspoon, Steven Kyle] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA OR05-6 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103147 ER PT J AU Tela, GH Dougher, CE Katz, ML Laffel, LM AF Tela, Gabriela H. Dougher, Carly E. Katz, Michelle L. Laffel, Lori M. TI Dynamic Changes in Total Daily Insulin Dose (U/kg/D) during Childhood and Adolescence in Youth with Type 1 Diabetes (T1D): Impact of Age, Sex, Regimen, and Weight Status SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Tela, Gabriela H.; Dougher, Carly E.; Katz, Michelle L.; Laffel, Lori M.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0952 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106215 ER PT J AU Teng, XC Jin, T Brent, GA Wu, AH Teng, WP Shan, ZY AF Teng, Xiaochun Jin, Ting Brent, Gregory A. Wu, An-hua Teng, Weiping Shan, Zhongyan TI A Girl with Resistance to Thyroid Hormone (P453T) and a Suspected Thyrotropin-Secreting Pituitary Microadenoma SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Teng, Xiaochun; Jin, Ting; Shan, Zhongyan] Inst Endocrinol, Shenyang, Peoples R China. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab,Dept Med, Tarzana, CA USA. [Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Tarzana, CA USA. [Wu, An-hua] Dept Neurosurg, Shenyang, Peoples R China. [Teng, Weiping] Endocrine Inst, Shenyang, Peoples R China. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0488 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805108315 ER PT J AU Thomou, T Mori, MA Kahn, CR AF Thomou, Thomas Mori, Marcelo A. Kahn, C. Ronald TI Adipose Tissue Micrornas Account for a Major Fraction of Circulating Exosomal microRNAs and Regulate mRNA Expression in Other Tissues SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Thomou, Thomas] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA. [Mori, Marcelo A.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0381 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100296 ER PT J AU Townsend, KL Chen, W Huang, TL Lessard, S Goodyear, LJ Babitt, J Lin, H Tseng, YH AF Townsend, Kristy L. Chen, Wenjie Huang, TianLian Lessard, Sarah Goodyear, Laurie J. Babitt, Jodie Lin, Herb Tseng, Yu-Hua TI Loss of BMP Co-Receptor Hemojuvelin Leads to Increased Brown Adipogenesis in Mice SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Townsend, Kristy L.; Huang, TianLian; Lessard, Sarah; Tseng, Yu-Hua] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA. [Chen, Wenjie; Babitt, Jodie; Lin, Herb] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goodyear, Laurie J.] Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0909 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805103051 ER PT J AU Tritos, NA Johannsson, G Korbonits, M Miller, KK Feldt-Rasmussen, U Yuen, KCJ King, D Mattsson, AF Jonsson, PJ Koltowska-Haggstrom, M Klibanski, A Biller, BMK AF Tritos, Nicholas A. Johannsson, Gudmundur Korbonits, Marta Miller, Karen K. Feldt-Rasmussen, Ulla Yuen, Kevin C. J. King, Donna Mattsson, Anders F. Jonsson, Peter J. Koltowska-Haggstrom, Maria Klibanski, Anne Biller, Beverly M. K. TI Long-Term Safety of Growth Hormone (GH) Replacement in Adults with GH Deficiency (GHD) Following Cure of Acromegaly a Kims (Pfizer International Metabolic Database) Analysis SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Tritos, Nicholas A.; Miller, Karen K.; Klibanski, Anne; Biller, Beverly M. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Johannsson, Gudmundur] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Korbonits, Marta] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med, London, England. [Feldt-Rasmussen, Ulla] Univ Copenhagen, Rigshosp, Copenhagen, Denmark. [Yuen, Kevin C. J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [King, Donna] Pfizer Inc, New York, NY USA. [Mattsson, Anders F.; Jonsson, Peter J.; Koltowska-Haggstrom, Maria] Pfizer Endocrine Care, Sollentuna, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA PP17-1 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805102107 ER PT J AU Tritos, NA Johannsson, G Korbonits, M Miller, KK Feldt-Rasmussen, U Yuen, KCJ King, D Mattsson, AF Jonsson, PJ Koltowska-Haggstrom, M Klibanski, A Biller, BMK AF Tritos, Nicholas A. Johannsson, Gudmundur Korbonits, Marta Miller, Karen K. Feldt-Rasmussen, Ulla Yuen, Kevin C. J. King, Donna Mattsson, Anders F. Jonsson, Peter J. Koltowska-Haggstrom, Maria Klibanski, Anne Biller, Beverly M. K. TI Long-Term Safety of Growth Hormone (GH) Replacement in Adults with GH Deficiency (GHD) Following Cure of Acromegaly - a Kims (Pfizer International Metabolic Database) Analysis SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Tritos, Nicholas A.; Miller, Karen K.; Klibanski, Anne; Biller, Beverly M. K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Johannsson, Gudmundur] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Korbonits, Marta] Queen Mary Univ London, Barts & London Sch Med, Wlliam Harvey Res Inst, London, England. [Feldt-Rasmussen, Ulla] Univ Copenhagen, Rigshosp, Copenhagen, Denmark. [Yuen, Kevin C. J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [King, Donna] Pfizer Inc, New York, NY USA. [Mattsson, Anders F.; Jonsson, Peter J.; Koltowska-Haggstrom, Maria] Pfizer Endocrine Care, Sollentuna, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0589 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805100317 ER PT J AU True, C Chan, YM Seminara, SB AF True, Cadence Chan, Yee-Ming Seminara, Stephanie Beth TI Estradiol Treatment Improves Estrous Cycling but Does Not Rescue All Reproductive Defects in Neurokinin B Receptor Deficient Mice SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [True, Cadence; Chan, Yee-Ming; Seminara, Stephanie Beth] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SUN-0672 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805109281 ER PT J AU Vaidya, A Baudrand, R Winberg, L Ruan, DT Shyn, P Dluhy, RG McKay, R Choueiri, T Elfiky, A AF Vaidya, Anand Baudrand, Rene Winberg, Linda Ruan, Daniel T. Shyn, Paul Dluhy, Robert G. McKay, Rana Choueiri, Toni Elfiky, Aymen TI The Impact of Repeated Cytoreduction in Combination with Maximal Medical Therapy on Clinical Outcomes and Quality of Life in Advanced Adrenal Cortical Carcinoma SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Vaidya, Anand; Winberg, Linda; Ruan, Daniel T.; Shyn, Paul; Dluhy, Robert G.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. [Baudrand, Rene] Pontificia Univ Catolica Chile, Santiago, Chile. [McKay, Rana; Choueiri, Toni; Elfiky, Aymen] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0801 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805101112 ER PT J AU von Eynatten, M Ross, S Caballero, E Del Prato, S Gallwitz, B Lewis-D'Agostino, D Bailes, Z Thiemannt, S Patel, S Woerle, HJ AF von Eynatten, Maximilian Ross, Stuart Caballero, Enrique Del Prato, Stefano Gallwitz, Baptist Lewis-D'Agostino, Diane Bailes, Zelie Thiemannt, Sandra Patel, Sanjay Woerle, Hans-Juergen TI Linagliptin Monotherapy Versus Initial Combination Therapy with Metformin in Patients with Newly Diagnosed Type 2 Diabetes (T2D): A Randomized Controlled Trial SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [von Eynatten, Maximilian] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Ross, Stuart] Univ Calgary, Calgary, AB, Canada. [Caballero, Enrique] Joslin Diabet Ctr, Boston, MA 02215 USA. [Del Prato, Stefano] Univ Pisa, Pisa, Italy. [Gallwitz, Baptist] Univ Klinikum Tuebingen, Tubingen, Germany. [Lewis-D'Agostino, Diane] Boeheringer Ingelheim, Ridgefield, CT USA. [Bailes, Zelie] Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England. [Thiemannt, Sandra] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany. [Patel, Sanjay] Boehringer Ingelheim Ltd, Bracknell, Berks, England. [Woerle, Hans-Juergen] Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA SAT-0987 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805106201 ER PT J AU Yu, EW Bouxsein, ML Monis, E Roy, A Butsch, WS Finkelstein, JS AF Yu, Elaine W. Bouxsein, Mary L. Monis, Elizabeth Roy, Adam Butsch, W. Scott Finkelstein, Joel Stephen TI Bariatric Surgery Patients Have Continued Bone Loss for 2 Years after Surgery Despite Weight Stabilization SO ENDOCRINE REVIEWS LA English DT Meeting Abstract C1 [Yu, Elaine W.; Bouxsein, Mary L.; Monis, Elizabeth; Roy, Adam; Butsch, W. Scott; Finkelstein, Joel Stephen] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD JUN PY 2014 VL 35 IS 3 SU S MA MON-0194 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V45GM UT WOS:000209805105056 ER PT J AU Walker, RJ Smalls, BL Hernandez-Tejada, MA Campbell, JA Egede, LE AF Walker, Rebekah J. Smalls, Brittany L. Hernandez-Tejada, Melba A. Campbell, Jennifer A. Egede, Leonard E. TI EFFECT OF DIABETES SELF-EFFICACY ON GLYCEMIC CONTROL, MEDICATION ADHERENCE, SELF-CARE BEHAVIORS, AND QUALITY OF LIFE IN A PREDOMINANTLY LOW-INCOME, MINORITY POPULATION SO ETHNICITY & DISEASE LA English DT Article DE Diabetes Self-efficacy; Glycemic Control; Medication Adherence; Self-care Behaviors; Quality of Life; Low-income Population; Type 2 Diabetes ID AFRICAN-AMERICAN; FOOD INSECURITY; SOCIOECONOMIC-STATUS; HEALTH LITERACY; MANAGEMENT; ADULTS; INTERVENTION; ASSOCIATION; PERCEPTIONS; STRATEGIES AB Objective: This study examined the effect of self-efficacy on glycemic control, self-care behaviors, and quality of life in low-income, minority adults with diabetes. Methods: Data on 378 participants were examined. Multiple linear regression assessed associations between self-efficacy, hemoglobin A1c, medication adherence, diabetes knowledge, self-care behaviors and quality of life. Results: Self-efficacy had modest correlations with glycemic control (r = -2.250, P < .001), medication adherence (r = -.352, P < .001), diabetes knowledge (r = -.118, P < .039), diet (r = -.420, P < .001), exercise (r = -.220, P < .001), blood sugar testing (r = -.213, P < .001), foot care (r = .121, P < .032), and mental health related quality of life (r = .137, P < .017). In the regression model, self-efficacy was significantly associated with glycemic control (beta = -.104, 95% CI: - .157, - .051), medication adherence (beta = -.067, 95% CI: - .090, - .044), diet (beta = .150, 95% CI:.108,.191), exercise (beta = -.113, 95% CI:.065,.161), blood sugar testing (beta = .107, 95% CI:.049,.164) and mental health related quality of life (beta = .112, 95% CI:.051,.173). Conclusion: Higher self-efficacy was associated with improved glycemic control, medication adherence, self-care behavior and mental health related quality of life. Practice Implications: Emphasis on self-efficacy is relevant for educational interventions developed for low-income, minority populations. C1 [Walker, Rebekah J.; Smalls, Brittany L.; Hernandez-Tejada, Melba A.; Campbell, Jennifer A.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Hlth Equity & Rural Outreach Innovat Ctr, Charleston VA COIN, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute for Diabetes, Digestive and Kidney Disease [T35DK007431] FX Supported by Grant #T35DK007431 from the National Institute for Diabetes, Digestive and Kidney Disease. NR 53 TC 9 Z9 10 U1 1 U2 9 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2014 VL 24 IS 3 BP 349 EP 355 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU7KT UT WOS:000363717300013 PM 25065078 ER PT J AU Boehme, AK McGwin, G Andes, DR Lyon, GM Chiller, T Pappas, PG Baddley, JW AF Boehme, Amelia K. McGwin, Gerald Andes, David R. Lyon, G. Marshall Chiller, Tom Pappas, Peter G. Baddley, John W. TI RACE AND INVASIVE FUNGAL INFECTION IN SOLID ORGAN TRANSPLANT RECIPIENTS SO ETHNICITY & DISEASE LA English DT Article DE Invasive Fungal Infection; Solid Organ Transplant; Aspergillosis; Candidiasis; Cryptococcosis ID SURVEILLANCE NETWORK TRANSNET; LIVER-TRANSPLANTATION; ETHNIC DISPARITIES; RISK-FACTORS; COCCIDIOIDOMYCOSIS; SURVIVAL; ACCESS AB Health disparities in access to solid organ transplantation (SOT) and graft survival are well recognized, but there are limited data on the relationship of race to risk of invasive fungal infection (IFI) among SOT recipients. We conducted a case-control study using data from the Transplant-Associated Infection Surveillance Network (TRANSNET) to investigate race and IFI. Cases (n=1,214) and controls (n=16,550) were compared on demographic variables using chi-square, and the relationship between race and IFI was assesses with unconditional logistic regression. Compared to White transplant patients, Blacks had similar odds of developing IFI (OR=.97, 95% CI 0.82-1.15, P=.7125), while participants who identified as other ethnicity were less likely to develop IFI (OR=.56, 95% CI .41-.75, P<.001). Blacks, when compared to White patients, were at increased odds of developing cryptococcal infection (OR 2.19, 95%CI 1.35-3.54, P=.002). Despite pharmacogenetic differences, Black transplant recipients were not more likely overall to develop IFI compared to White transplant recipients. C1 [Boehme, Amelia K.] Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA. [Andes, David R.] Univ Wisconsin, Madison, WI 53706 USA. [Lyon, G. Marshall] Emory Univ, Sch Med, Atlanta, GA 30322 USA. [Chiller, Tom] Ctr Dis Control, Atlanta, GA 30333 USA. [Pappas, Peter G.; Baddley, John W.] Univ Alabama Birmingham, Sch Med, Birmingham, AL 35294 USA. [Baddley, John W.] Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Baddley, JW (reprint author), Univ Alabama Birmingham, Div Infect Dis, 1900 Univ Blvd,THT 229, Birmingham, AL 35294 USA. EM jbaddley@uab.edu FU CDC; Astellas; Pfizer; Merck; Schering Plough FX TRANSNET was sponsored by the CDC, Astellas, Pfizer, Merck, and Schering Plough. We would like to thank the following TRANSNET Investigators: Barbara Alexander, MD, Duke University; Elias Anaissie, MD, University of Arkansas; Michael Boeckh, MD, Fred Hutchinson Cancer Research Center; Janice Brown, MD, Stanford University; Lisa Brumble, MD, Mayo Clinic-Jacksonville; Alison Freifeld, MD, University of Nebraska; Yoav Golan, MD, and Susan Hadley, MD, Tufts University; Loreen Herwaldt, MD, University of Iowa; James Ito, MD, City of Hope National Medical Center; Carol Kauffman, MD, University of Michigan; Katherine Knapp, MD, St. Jude Children's Hospital; Dimitrios Kontoyiannis, MD, MD Anderson Cancer Center; Kieren Marr, MD and Trish Perl, MD, Johns Hopkins Medical Institute; Vicki Morrison, MD, University of Minnesota; Genovefa Papanicolaou, MD, Memorial Sloan-Kettering Cancer Center; Tom Patterson, MD, University of Texas HSC-San Antonio; Mindy Schuster, MD, University of Pennsylvania; Randall Walker, MD, Mayo Clinic-Rochester; Tom Walsh, MD, Weill Cornell Medical College; John Wingard, MD, University of Florida. NR 17 TC 1 Z9 1 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X EI 1945-0826 J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2014 VL 24 IS 3 BP 382 EP 385 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CU7KT UT WOS:000363717300018 PM 25065083 ER PT J AU Khamis, RY Woollard, KJ Hyde, GD Boyle, JJ Bicknell, C Hara, T Mauskapf, A Granger, DW Johnson, JL Ntziachristos, V Matthews, PM Jaffer, FA Haskard, DO AF Khamis, Ramzi Y. Woollard, Kevin J. Hyde, Gareth D. Boyle, Joseph J. Bicknell, Colin Hara, Tetsuya Mauskapf, Adam Granger, David W. Johnson, Jason L. Ntziachristos, Vasilis Matthews, Paul M. Jaffer, Farouc A. Haskard, Dorian O. TI DEVELOPMENT OF WHOLE BODY AND INTRAVASCULAR NEAR-INFRARED OPTICAL MOLECULAR IMAGING OF MARKERS OF PLAQUE VULNERABLITY IN ATHEROSCLEROSIS SO HEART LA English DT Meeting Abstract CT Annual Conference of the British-Cardiovascular-Society CY JUN 02-04, 2014 CL Manchester, ENGLAND SP British Cardiovascular Soc C1 [Khamis, Ramzi Y.; Hyde, Gareth D.; Boyle, Joseph J.; Haskard, Dorian O.] Univ London Imperial Coll Sci Technol & Med, Natl Hearth & Lung Inst, Vasc Sci Sect, London SW7 2AZ, England. [Woollard, Kevin J.; Matthews, Paul M.] Univ London Imperial Coll Sci Technol & Med, Dept Med, London SW7 2AZ, England. [Bicknell, Colin] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London SW7 2AZ, England. [Hara, Tetsuya; Mauskapf, Adam; Ntziachristos, Vasilis; Jaffer, Farouc A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Cambridge, MA 02138 USA. [Hara, Tetsuya; Mauskapf, Adam; Ntziachristos, Vasilis; Jaffer, Farouc A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Cambridge, MA 02138 USA. [Granger, David W.] GlaxoSmithKline, Biopharm R&D, Stevenage, Herts, England. [Johnson, Jason L.] Univ Bristol, Bristol Heart Inst, Bristol, Avon, England. OI Khamis, Ramzi /0000-0003-4119-5193 FU British Heart Foundation [FS/07/053/24069] NR 0 TC 0 Z9 0 U1 1 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD JUN PY 2014 VL 100 SU 3 MA C BP A128 EP A128 DI 10.1136/heartjnl-2014-306118.231 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CP5UR UT WOS:000359951000233 ER PT J AU Chatterjee, NA Upadhyay, GA Singal, G Parks, KA Dec, GW Singh, JP Lewis, GD AF Chatterjee, Neal A. Upadhyay, Gaurav A. Singal, Gaurav Parks, Kimberly A. Dec, G. William Singh, Jagmeet P. Lewis, Gregory D. TI Pre-Capillary Pulmonary Hypertension and Right Ventricular Dilation Predict Clinical Outcome in Cardiac Resynchronization Therapy SO JACC-HEART FAILURE LA English DT Article DE cardiac resynchronization therapy; pulmonary hypertension; right ventricle ID CHRONIC HEART-FAILURE; ARTERY PRESSURE; EJECTION FRACTION; SYSTOLIC PRESSURE; MORTALITY; CARDIOMYOPATHY; EXERCISE; RISK; ECHOCARDIOGRAPHY; TRANSPLANTATION AB Objectives This study examined the prognostic significance of pre- and post-capillary components of pulmonary hypertension (PH) in patients receiving cardiac resynchronization therapy (CRT). Background PH is common in patients with left ventricular systolic dysfunction (LVSD) receiving CRT. The impact of PH subtype on clinical outcome in CRT is unknown. Methods The study population consisted of 101 patients (average age 66 +/- 13 years, left ventricular ejection fraction 0.23 +/- 0.07, and New York Heart Association functional class 3.2 +/- 0.4) who underwent right heart catheterization in the 6 months before CRT. PH was defined as a mean pulmonary artery pressure >= 25 mm Hg; a significant pre-capillary contribution to elevated mean pulmonary artery pressure was defined as a transpulmonary gradient (TPG) >= 12 mm Hg. Clinical endpoints were assessed at 2 years and included all-cause mortality and a composite of death, left ventricular assist device, or cardiac transplantation. Results Patients with TPG >= 12 mm Hg were more likely to experience all-cause mortality (hazard ratio [HR]: 3.2; 95% confidence interval [CI]: 1.3 to 7.4; p = 0.009) and the composite outcome (HR: 3.0; 95% CI: 1.4 to 6.3; p = 0.004) compared with patients with TPG <12 mm Hg. After multivariate adjustment for hemodynamic, clinical, and echocardiographic variables, only TPG >= 12 mm Hg and baseline right ventricular (RV) dilation (RV end-diastolic dimension >42 mm) were associated with the composite clinical outcome (p = 0.05 and p = 0.04, respectively). Conclusions High TPG PH and RV dilation are independent predictors of adverse outcomes in patients with LVSD who are receiving CRT. RV pulmonary vascular dysfunction may be a therapeutic target in select patients receiving CRT. (C) 2014 by the American College of Cardiology Foundation C1 [Chatterjee, Neal A.; Upadhyay, Gaurav A.; Singal, Gaurav; Parks, Kimberly A.; Dec, G. William; Singh, Jagmeet P.; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Upadhyay, Gaurav A.; Singal, Gaurav; Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. [Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM glewis@partners.org FU National Heart Lung and Blood Institute (National Institutes of Health) [K23HL091106]; Heart Failure Innovation Fund FX Dr. Lewis has received support from the National Heart Lung and Blood Institute (National Institutes of Health K23HL091106) and the Heart Failure Innovation Fund. All other authors have reported they have no relationships relevant to the contents of this paper to disclose. NR 39 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD JUN PY 2014 VL 2 IS 3 BP 230 EP 237 DI 10.1016/j.jchf.2014.02.004 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4DC UT WOS:000365647600005 PM 24952689 ER PT J AU Krezanoski, PJ Tsai, AC Hamer, DH Comfort, AB Bangsberg, DR AF Krezanoski, Paul J. Tsai, Alexander C. Hamer, Davidson H. Comfort, Alison B. Bangsberg, David R. TI Household malaria knowledge and its association with bednet ownership in settings without large-scale distribution programs: Evidence from rural Madagascar SO JOURNAL OF GLOBAL HEALTH LA English DT Article AB Background Insecticide-treated bednets are effective at preventing malaria. This study focuses on household-level factors that are associated with bednet ownership in a rural area of Madagascar which had not been a recipient of large-scale ITN distribution. Methods Data were gathered on individual and household characteristics, malaria knowledge, household assets and bednet ownership. Principal components analysis was used to construct both a wealth index based on household assets and a malaria knowledge index based on responses to questions about malaria. Bivariate and multivariate regressions were used to determine predictors of household bednet ownership and malaria knowledge. Results Forty-seven of 560 households (8.4%) owned a bednet. In multivariate analysis, higher level of malaria knowledge among household members was the only variable significantly associated with bednet ownership (odds ratio 3.72, P < 0.001). Among respondents, predictors of higher malaria knowledge included higher education levels, female sex and reporting fever as the most frequent or dangerous illness in the community. Household wealth was not a significant predictor of bednet ownership or respondent malaria knowledge. Conclusion In this setting of limited supply of affordable bednets, malaria knowledge was associated with an increased probability of household bednet ownership. Further studies should determine how such malaria knowledge evolves and if malaria-specific education programs could help overcome the barriers to bednet ownership among at-risk households living outside the reach of large-scale bednet distribution programs. C1 [Krezanoski, Paul J.] Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. [Krezanoski, Paul J.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Tsai, Alexander C.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Hamer, Davidson H.] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02215 USA. [Hamer, Davidson H.] Boston Univ, Sch Publ Hlth, Dept Int Hlth, Boston, MA USA. [Hamer, Davidson H.] ZCAHRD, Lusaka, Zambia. [Hamer, Davidson H.] Boston Univ, Med Ctr, Dept Med, Infect Dis Sect, Boston, MA USA. [Comfort, Alison B.] Abt Associates Inc, Int Hlth Div, Cambridge, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bangsberg, David R.] Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda. RP Krezanoski, PJ (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM pkrezanoski@partners.org FU NIH [K23MH096620] FX All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare that Dr A. C. Tsai reports grant from NIH for the research outside the submitted work (grant No. K23MH096620). Other authors declare no support from any organization for the submitted work; no financial relationships with other organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work. NR 29 TC 2 Z9 2 U1 0 U2 3 PU UNIV EDINBURGH, GLOBAL HEALTH SOC PI EDINBURGH PA CENTRE POPULATION HEALTH SCIENCES, TEVIOT PL, EDINBURGH, EH8 9AG, ENGLAND SN 2047-2978 EI 2047-2986 J9 J GLOB HEALTH JI J. Glob. Health PD JUN PY 2014 VL 4 IS 1 AR 010401 DI 10.7189/jogh.04.010401 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V42SJ UT WOS:000209633200006 PM 24976960 ER PT J AU Ferry, JA AF Ferry, Judith A. TI The diversity of diffuse large B-cell lymphoma in extranodal sites: overview and update SO JOURNAL OF HEMATOPATHOLOGY LA English DT Review DE B-cell lymphomas; Diffuse large B-cell lymphoma; Primary central nervous system; Extranodal; Skin; Mediastinum; EBV; HHV8 ID CENTRAL-NERVOUS-SYSTEM; PRIMARY-EFFUSION-LYMPHOMA; SARCOMA-ASSOCIATED HERPESVIRUS; CLASSICAL HODGKIN LYMPHOMA; NEGATIVE PLASMABLASTIC LYMPHOMA; GRAY ZONE LYMPHOMA; INTRAVASCULAR LYMPHOMA; KAPOSIS-SARCOMA; CLINICAL PRESENTATION; CHRONIC INFLAMMATION AB Extranodal lymphomas are a diverse group of low and high grade neoplasms of B-, T-, and NK-cell lineage, each with characteristic sites of origin, morphology, immunophenotype, genetic features, patterns of spread, and prognosis. The diversity is sometimes seen even within a single histologic type of lymphoma. This phenomenon is especially striking in the category of diffuse large B-cell lymphoma (DLBCL). DLBCLs as classified in the WHO Classification are clinically and pathologically heterogeneous (Swerdlow et al. 2008; Stein et al. 2008). Since the publication of the most recent edition of the WHO Classification of tumours of haematopoietic and lymphoid tissues (Swerdlow et al. 2008), a number of advances in the understanding of these lymphomas have been made. This review provides an overview of extranodal DLBCLs and describes recent updates regarding these lymphomas. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM jferry@partners.org NR 115 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1868-9256 EI 1865-5785 J9 J HEMATOP JI J. Hematop. PD JUN PY 2014 VL 7 IS 2 BP 57 EP 70 DI 10.1007/s12308-014-0202-7 PG 14 WC Hematology; Pathology SC Hematology; Pathology GA CU7YQ UT WOS:000363758200003 ER PT J AU Weingart, SN Zhu, JY Young-Hong, J Vermilya, HB Hassett, M AF Weingart, Saul N. Zhu, Junya Young-Hong, Joanne Vermilya, Holly Barr Hassett, Michael TI Do drug interaction alerts between a chemotherapy order- entry system and an electronic medical record affect clinician behavior? SO JOURNAL OF ONCOLOGY PHARMACY PRACTICE LA English DT Article DE Oral antineoplastic therapy; medication safety; electronic medical record; alerts and reminders ID AMBULATORY-CARE; SAFETY; ERRORS; CANCER; PREVENTION; CHILDREN; EVENTS AB Introduction We developed an enhancement to a chemotherapy order-entry system that alerted prescribers to potential drug interactions between patients' usual outpatient medications and those prescribed for onsite cancer treatment. This report summarizes the interactions and analyzes the impact of alerts on clinician behavior. Methods We studied electronic orders created from November 2010 to December 2011 by oncology clinicians at two comprehensive cancer centers who shared a chemotherapy order-entry system and an ambulatory electronic medical record. The enhancement generated an alert if a new chemotherapy system order for an antineoplastic agent or supportive care medication interacted with an existing medication in the ambulatory record, and tracked prescribers' responses. Results New chemotherapy system orders triggered 29,592 drug interaction alerts. New orders for antineoplastic agents accounted for 495 (32.6%) of 1518 high- and medium-severity alerts. Interactions with antibiotics accounted for the majority of these alerts. New chemotherapy system orders for antiemetics triggered 352 (23.2%) alerts and more than two-thirds were attributed to interactions with analgesic opioids. High- and medium-severity alerts changed prescriber behavior in 224 (14.8%) occurrences, including potentially fatal interactions between meperidine and monoamine oxidase inhibitors. Clinicians who overrode alerts indicated that they would monitor the patient (54.6%), the patient already tolerated the combination (24.5%), and they would adjust the dose (15.1%). Conclusion Cancer patients are at risk of serious interactions between medications ordered for cancer care and those provided for general medical care. Organizations and order-entry applications should develop countermeasures to identify and prevent potentially serious drug interactions. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safety, 450 Brookline Ave, Boston, MA 02215 USA. EM saul_weingart@dfci.harvard.edu NR 19 TC 0 Z9 0 U1 1 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1078-1552 EI 1477-092X J9 J ONCOL PHARM PRACT JI J. Oncol. Pharm. Pract. PD JUN PY 2014 VL 20 IS 3 BP 163 EP 171 DI 10.1177/1078155213487395 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AG1XR UT WOS:000335210000001 PM 23804625 ER PT J AU Ali, SF Viswanathan, A Singhal, AB Rost, NS Forducey, PG Davis, LW Schindler, J Likosky, W Schlegel, S Solenski, N Schwamm, LH AF Ali, Syed F. Viswanathan, Anand Singhal, Aneesh B. Rost, Natalia S. Forducey, Pamela G. Davis, Lawrence W. Schindler, Joseph Likosky, William Schlegel, Sherene Solenski, Nina Schwamm, Lee H. CA Partners Telestroke Network TI The TeleStroke Mimic (TM)-Score: A Prediction Rule for Identifying Stroke Mimics Evaluated in a Telestroke Network SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE cerebrovascular disease; stroke mimics; telestroke; thrombolysis AB Background-Up to 30% of acute stroke evaluations are deemed stroke mimics (SM). As telestroke consultation expands across the world, increasing numbers of SM patients are likely being evaluated via Telestroke. We developed a model to prospectively identify ischemic SMs during Telestroke evaluation. Methods and Results-We analyzed 829 consecutive patients from January 2004 to April 2013 in our internal New England-based Partners TeleStroke Network for a derivation cohort, and 332 cases for internal validation. External validation was performed on 226 cases from January 2008 to August 2012 in the Partners National TeleStroke Network. A predictive score was developed using stepwise logistic regression, and its performance was assessed using receiver-operating characteristic (ROC) curve analysis. There were 23% SM in the derivation, 24% in the internal, and 22% in external validation cohorts based on final clinical diagnosis. Compared to those with ischemic cerebrovascular disease (iCVD), SM had lower mean age, fewer vascular risk factors, more frequent prior seizure, and a different profile of presenting symptoms. The TeleStroke Mimic Score (TM-Score) was based on factors independently associated with SM status including age, medical history (atrial fibrillation, hypertension, seizures), facial weakness, and National Institutes of Health Stroke Scale >14. The TM-Score performed well on ROC curve analysis (derivation cohort AUC=0.75, internal validation AUC=0.71, external validation AUC=0.77). Conclusions-SMs differ substantially from their iCVD counterparts in their vascular risk profiles and other characteristics. Decision-support tools based on predictive models, such as our TM Score, may help clinicians consider alternate diagnosis and potentially detect SMs during complex, time-critical telestroke evaluations. C1 [Ali, Syed F.; Viswanathan, Anand; Singhal, Aneesh B.; Rost, Natalia S.; Schwamm, Lee H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Forducey, Pamela G.; Davis, Lawrence W.] INTEGRIS Hlth, Oklahoma City, OK USA. [Schindler, Joseph] Yale New Haven Stroke Ctr, New Haven, CT USA. [Likosky, William; Schlegel, Sherene] Swedish Med Ctr, Seattle, WA USA. [Solenski, Nina] Univ Virginia, Charlottesville, VA USA. RP Schwamm, LH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,MGH Stroke Serv, 55 Fruit St, Boston, MA 02114 USA. EM lschwamm@partners.org FU Principal Investigator of an National Institute of Neurological Disorders and Stroke; Health Resource Services Administration Requisition [09-HRS9923-AB] FX Syed F. Ali, Anand Viswanathan, Aneesh B. Singhal, Natalia S. Rost, Pamela G. Forducey, Lawrence W. Davis, Joseph Schindler, William Likosky, Sherene Schlegel, and Nina Solenski all report no disclosures. Dr Schwamm serves as a consultant to the Massachusetts Department of Public Health, and is the Medical Director of the Mass General TeleHealth program and the Partners TeleStroke Center. Massachusetts General Hospital provides telehealth services to hospitals in the New England region, including telestroke. Dr Schwamm is the Principal Investigator of an National Institute of Neurological Disorders and Stroke-funded SPOTRIAS center clinical trial, MR WITNESS, for which Genentech provides alteplase and additional funding. His work is supported in part by Health Resource Services Administration Requisition 09-HRS9923-AB (Stroke and Traumatic Brain Injury Telehealth Services). NR 27 TC 6 Z9 6 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000838 DI 10.1161/JAHA.114.000838 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41RD UT WOS:000209562400001 PM 24958778 ER PT J AU Coelho, OR Shah, RV Neilan, TG Mitchell, R Moreno, H Kwong, R Jerosch-Herold, M AF Coelho-Filho, Otavio R. Shah, Ravi V. Neilan, Tomas G. Mitchell, Richard Moreno, Heitor, Jr. Kwong, Raymond Jerosch-Herold, Michael TI Cardiac Magnetic Resonance Assessment of Interstitial Myocardial Fibrosis and Cardiomyocyte Hypertrophy in Hypertensive Mice Treated With Spironolactone SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE cardiac magnetic resonance imaging; hypertension; hypertrophy/remodeling AB Background-Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR). Methods and Results-Mice were randomized to L-nitro-omega-methyl ester (L-NAME, 3 mg/mL in water; n=22), or L-NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (sic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of L-NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and sic compared with placebo-treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and L-NAME ("L-NAME+S") showed less concentric remodeling, and a lower myocardial ECV and sic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43 +/- 0.09 for L-NAME versus 0.25 +/- 0.03 for L-NAME+S, P<0.001; tau(ic): 0.42 +/- 0.11 for L-NAME groups versus 0.12 +/- 0.05 for L-NAME+S group). Mice treated with a combination of L-NAME and spironolactone were similar to placebo-treated controls at 7 weeks. Conclusions-Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure-overload, furthering our understanding of HF progression. C1 [Coelho-Filho, Otavio R.; Shah, Ravi V.; Neilan, Tomas G.; Kwong, Raymond] Harvard Univ, Sch Med, Dept Med, Div Cardiovasc, Boston, MA USA. [Jerosch-Herold, Michael] Harvard Univ, Sch Med, Dept Radiol, Div Cardiovasc, Boston, MA 02115 USA. [Mitchell, Richard] Harvard Univ, Sch Med, Dept Pathol, Div Cardiovasc, Boston, MA 02115 USA. [Coelho-Filho, Otavio R.; Moreno, Heitor, Jr.] State Univ Campinas UNICAMP, Dept Internal Med, Sao Paulo, Brazil. [Neilan, Tomas G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Radiol,Dept Med, Boston, MA USA. [Neilan, Tomas G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. [Neilan, Tomas G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. RP Jerosch-Herold, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St,Radiol BWH Box 22, Boston, MA 02115 USA. EM mjerosch-herold@partners.org FU National Heart, Lung, and Blood Institute of the National Institutes of Health [R01HL090634]; American Heart Association [AHA 11POST5550053, AHA 11POST110033]; American Heart Association Fellow-to-Faculty grant [12FTF12060588] FX The Research reported in this publication was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under Award Number R01HL090634. Drs Coelho-Filho and Shah are supported by Post-Doctoral Fellowships from the American Heart Association (AHA 11POST5550053 to OCF and AHA 11POST110033 to RVS). Dr Neilan is supported by an American Heart Association Fellow-to-Faculty grant (12FTF12060588). NR 46 TC 6 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000790 DI 10.1161/JAHA.114.000790 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41RD UT WOS:000209562400009 PM 24965024 ER PT J AU Liu, Y Syed, Z Scirica, BM Morrow, DA Guttag, JV Stultz, CM AF Liu, Yun Syed, Zeeshan Scirica, Benjamin M. Morrow, David A. Guttag, John V. Stultz, Collin M. TI ECG Morphological Variability in Beat Space for Risk Stratification After Acute Coronary Syndrome SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE morphological variability; risk stratification acute coronary syndrome AB Background-Identification of patients who are at high risk of adverse cardiovascular events after an acute coronary syndrome (ACS) remains a major challenge in clinical cardiology. We hypothesized that quantifying variability in electrocardiogram (ECG) morphology may improve risk stratification post-ACS. Methods and Results-We developed a new metric to quantify beat-to-beat morphologic changes in the ECG: morphologic variability in beat space (MVB), and compared our metric to published ECG metrics (heart rate variability [HRV], deceleration capacity [DC], T-wave alternans, heart rate turbulence, and severe autonomic failure). We tested the ability of these metrics to identify patients at high risk of cardiovascular death (CVD) using 1082 patients (1-year CVD rate, 4.5%) from the MERLIN-TIMI 36 (Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36) clinical trial. DC, HRV/low frequency-high frequency, and MVB were all associated with CVD (hazard ratios [HRs] from 2.1 to 2.3 [P<0.05 for all] after adjusting for the TIMI risk score [TRS], left ventricular ejection fraction [LVEF], and B-type natriuretic peptide [BNP]). In a cohort with low-to-moderate TRS (N=864; 1-year CVD rate, 2.7%), only MVB was significantly associated with CVD (HR, 3.0; P=0.01, after adjusting for LVEF and BNP). Conclusions-ECG morphological variability in beat space contains prognostic information complementary to the clinical variables, LVEF and BNP, in patients with low-to-moderate TRS. ECG metrics could help to risk stratify patients who might not otherwise be considered at high risk of CVD post-ACS. C1 [Liu, Yun; Stultz, Collin M.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Liu, Yun; Stultz, Collin M.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Syed, Zeeshan] Univ Michigan, Elect & Comp Engn, Ann Arbor, MI 48109 USA. [Scirica, Benjamin M.; Morrow, David A.] Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Scirica, Benjamin M.; Morrow, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Guttag, John V.; Stultz, Collin M.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Stultz, CM (reprint author), Room 36-796,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM cmstultz@mit.edu FU Agency of Science, Technology and Research (A*STAR), Singapore; Quanta Computer, Taiwan; General Electric; Gilead Sciences FX This work was funded by the Agency of Science, Technology and Research (A*STAR), Singapore, Quanta Computer, Taiwan, and General Electric, USA MERLIN-TIMI 36 was supported by CV Therapeutics (now Gilead Sciences). NR 40 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000981 DI 10.1161/JAHA.114.000981 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41RD UT WOS:000209562400018 PM 24963105 ER PT J AU McCabe, JM Kennedy, KF Yeh, RW AF McCabe, James M. Kennedy, Kevin F. Yeh, Robert W. TI Defining Unavoidable Delays in Primary Percutaneous Coronary Intervention: Discordance Among Patients Excluded From National Cardiovascular Quality Registries SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE Centers for Medicare and Medicaid Services; NCDR; nonsystems delays; primary percutaneous coronary intervention AB Background-The Centers for Medicaid and Medicare Services (CMS) and the National Cardiovascular Data Registry (NCDR) track primary percutaneous coronary intervention (PCI) performance in the form of door-to-balloon time. For quality assessment, exceptions are made for patients with "unavoidable delays" in both registries, yet it remains unclear how consistently such patients are identified. Methods and Results-All primary PCI patients at 3 Massachusetts hospitals (Brigham and Women's, Massachusetts General, and North Shore Medical Center) from 2009 to 2011 were evaluated for CMS inclusion/exclusion and NCDR nonsystems delay (NSD) status. We subsequently analyzed patient characteristics and outcomes based on these strata. Among 456 total patients, 128 (28%) were excluded from CMS reporting, whereas 56 (12%) were listed in the NCDR registry as having an NSD. Forty of 56 (71%) patients with NSD were also excluded from CMS reporting, whereas 312 of 400 (78%) patients reported without NSD were included in CMS reports. Between-registry agreement on patients with unavoidable delays was modest (kappa=0.32). Among CMS-included patients without NSD, 94% received PCI within 90 minutes compared with 29% of CMS-excluded patients with NSD (P<0.001). Likewise, CMS-included patients without NSD had a 4-fold better 1-year mortality rate compared with CMS-excluded patients with NSD (P<0.001). Conclusions-More than twice as many primary PCI patients are excluded from CMS quality analyses compared with NCDR. With the use of currently available cardiovascular quality registries, it is unclear how many patients truly require unavoidable delays during primary PCI. Patients with NSD had the worst outcomes regardless of CMS status. C1 [McCabe, James M.] Univ Washington, Div Cardiol, Seattle, WA 98195 USA. [Kennedy, Kevin F.] St Lukes Mid Amer Heart Inst, Div Cardiol, Kansas City, MO USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP McCabe, JM (reprint author), Div Cardiol, 1959 NE Pacific St,Box 356422, Seattle, WA 98195 USA. EM mccabe@aya.yale.edu FU Long-term Outcomes Registry; American Heart Association FX Funding for this project was provided via the Long-term Outcomes Registry and a grant from the American Heart Association. Neither funding source participated in the design, conduct, analysis, or interpretation of the data. NR 12 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000944 DI 10.1161/JAHA.114.000944 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41RD UT WOS:000209562400021 PM 24965027 ER PT J AU Wimmer, NJ Spertus, JA Kennedy, KF Anderson, HV Curtis, JP Weintraub, WS Singh, M Rumsfeld, JS Masoudi, FA Yeh, RW AF Wimmer, Neil J. Spertus, John A. Kennedy, Kevin F. Anderson, H. Vernon Curtis, Jeptha P. Weintraub, William S. Singh, Mandeep Rumsfeld, John S. Masoudi, Frederick A. Yeh, Robert W. TI Clinical Prediction Model Suitable for Assessing Hospital Quality for Patients Undergoing Carotid Endarterectomy SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE carotid endarterectomy; risk prediction; stroke AB Background-Assessing hospital quality in the performance of carotid endarterectomy (CEA) requires appropriate risk adjustment across hospitals with varying case mixes. The aim of this study was to develop and validate a prediction model to assess the risk of in-hospital stroke or death after CEA that could aid in the assessment of hospital quality. Methods and Results-Patients from National Cardiovascular Data Registry (NCDR)'s Carotid Artery Revascularization and Endarterectomy (CARE) Registry undergoing CEA without acute evolving stroke from 2005 to 2013 were included. In-hospital stroke or death was modeled using hierarchical logistic regression with 20 candidate variables and accounting for hospital-level clustering. Internal validation was achieved with bootstrapping; model discrimination and calibration were assessed. A total of 213 (1.7%) primary end point events occurred during 12 889 procedures. Independent predictors of stroke or death included age, prior peripheral artery disease, diabetes mellitus, prior coronary artery disease, having a symptomatic carotid lesion, having a contralateral carotid occlusion, or having New York Heart Association Class III or IV heart failure. The model was well calibrated and demonstrated moderate discriminative ability (c-statistic 0.65). The NCDR CEA score was then developed to support simple, prospective risk quantification in the clinical setting. Conclusions-The NCDR CEA score, comprising 7 clinical variables, predicts in-hospital stroke or death after CEA. This model can be used to estimate hospital risk-adjusted outcomes for CEA and to assist with the assessment of hospital quality. C1 [Wimmer, Neil J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wimmer, Neil J.; Yeh, Robert W.] Harvard Univ, Sch Med, Boston, MA USA. [Spertus, John A.; Kennedy, Kevin F.] St Lukes Midamer Heart Inst, Kansas City, MO USA. [Anderson, H. Vernon] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA. [Curtis, Jeptha P.] Yale Univ, Sch Med, New Haven, CT USA. [Weintraub, William S.] Christiana Hlth Care, Newark, DE USA. [Singh, Mandeep] Mayo Clin, Rochester, MN USA. [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Masoudi, Frederick A.] Univ Colorado, Aurora, CO USA. [Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Yeh, RW (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM ryeh@partners.org FU American College of Cardiology Foundation's NCDR; CARE Registry is an initiative of the American College of Cardiology Foundation (ACCF); Society for Cardiovascular Angiography and Interventions; Society of Interventional Radiology; American Academy of Neurology; American Association of Neurological Surgeons/Congress of Neurological Surgeons; Society for Vascular Medicine; Society of Vascular and Interventional Neurology FX This research was supported by the American College of Cardiology Foundation's NCDR. The views expressed in this manuscript represent those of the author(s) and do not necessarily represent the official views of the NCDR or its associated professional societies identified at www.ncdr.com. Partners and Sponsors: CARE Registry is an initiative of the American College of Cardiology Foundation (ACCF), The Society for Cardiovascular Angiography and Interventions, the Society of Interventional Radiology, the American Academy of Neurology, the American Association of Neurological Surgeons/Congress of Neurological Surgeons, the Society for Vascular Medicine, and the Society of Vascular and Interventional Neurology. NR 24 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2014 VL 3 IS 3 AR e000728 DI 10.1161/JAHA.113.000728 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41RD UT WOS:000209562400033 PM 24938712 ER PT J AU Molina, Y Lehavot, K Beadnell, B Simoni, J AF Molina, Yamile Lehavot, Keren Beadnell, Blair Simoni, Jane TI Racial Disparities in Health Behaviors and Conditions Among Lesbian and Bisexual Women: The Role of Internalized Stigma SO LGBT HEALTH LA English DT Article DE bisexual; health disparities; lesbian/gay; physical health; race/ethnicity; women ID FEMINIST IDENTITY DEVELOPMENT; ACTIVITY QUESTIONNAIRE IPAQ; BODY-FAT DISTRIBUTION; SEXUAL ORIENTATION; AFRICAN-AMERICAN; PHYSICAL-ACTIVITY; US ADULTS; GAY MEN; PSYCHOLOGICAL DISTRESS; VEGETABLE INTAKE AB There are documented disparities in physical health behaviors and conditions, such as physical activity and obesity, with regard to both race/ethnicity and sexual orientation. However, physical health disparities for lesbian and bisexual (LB) women who are also racial minorities are relatively unexplored. Minority stressors, such as internalized stigma, may account for disparities in such multiply marginalized populations. We sought to (1) characterize inequalities among non-Hispanic white and African American LB women and (2) examine the roles of internalized sexism and homophobia in disparities. Data on health behaviors (diet, physical activity); physical health (hypertension, diabetes, overweight/obesity); internalized sexism; and internalized homophobia were collected via a web-based survey. Recruitment ads were sent electronically to over 200 listservs, online groups, and organizations serving the lesbian, gay, and bisexual community in all 50 U.S. states. The analytic sample consisted of 954 white and 75 African American LB women. African American participants were more likely than white participants to report low fruit/vegetable intake and physical activity, a higher body mass index, and a history of diabetes and hypertension. There were no racial differences in internalized homophobia, but African American women reported higher levels of internalized sexism. Internalized sexism partially mediated racial disparities in physical activity and diabetes, but not in the other outcomes. Findings suggest that African American LB women may be at greater risk than their white counterparts for poor health and that internalized sexism may be a mediator of racial differences for certain behaviors and conditions. C1 [Molina, Yamile] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Molina, Yamile] Univ Illinois, Epidemiol & Biostat Div, Chicago, IL USA. [Molina, Yamile] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Lehavot, Keren] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Beadnell, Blair] Univ Washington, Sch Social Work, Seattle, WA 98195 USA. [Simoni, Jane] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. [Lehavot, Keren] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Molina, Y (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA. EM ymolina@fhcrc.org OI Simoni, Jane/0000-0002-8711-1576 FU Centers for Disease Control Grant for Public Health Research Dissertation [R36 CD000996]; National Cancer Institute Supplement to Promote Diversity in Health-Related Research [P50CA148143]; Biobehavioral Cancer Prevention and Control Training Program at the University of Washington [R25CA92408] FX This research was supported by a Centers for Disease Control Grant for Public Health Research Dissertation (R36 CD000996) award to K.L. Manuscript preparation was supported by funding to Y.M. through a National Cancer Institute Supplement to Promote Diversity in Health-Related Research (P50CA148143) and a postdoctoral fellowship through the Biobehavioral Cancer Prevention and Control Training Program at the University of Washington (R25CA92408). NR 89 TC 3 Z9 3 U1 3 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2325-8292 EI 2325-8306 J9 LGBT HEALTH JI LGBT Health PD JUN PY 2014 VL 1 IS 2 BP 131 EP 139 DI 10.1089/lgbt.2013.0007 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CR9PV UT WOS:000361689800012 PM 25364769 ER PT J AU Robbins, NM Swanson, RA AF Robbins, Nathaniel M. Swanson, Raymond A. TI Opposing Effects of Glucose on Stroke and Reperfusion Injury Acidosis, Oxidative Stress, and Energy Metabolism SO STROKE LA English DT Article DE acidosis; hemorrhage; hyperglycemia; hypoglycemia; reactive oxygen species; superoxides C1 [Robbins, Nathaniel M.; Swanson, Raymond A.] Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. [Swanson, Raymond A.] San Francisco VA Med Ctr, Neurol Serv, San Francisco, CA USA. RP Swanson, RA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA.; Swanson, RA (reprint author), Dept Vet Affairs Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM raymond.swanson@ucsf.edu OI Swanson, Raymond/0000-0002-3664-5359 FU National Institutes of Health [NS041421, NS081149]; Department of Veterans Affairs FX This review was supported by National Institutes of Health grants NS041421 and NS081149 to R.A. Swanson and by the Department of Veterans Affairs. NR 48 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD JUN PY 2014 VL 45 IS 6 BP 1881 EP 1886 DI 10.1161/STROKEAHA.114.004889 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA V42VQ UT WOS:000209641700001 PM 24743441 ER PT J AU Banerjee, SC Hay, JL Geller, AC Gagne, JJ Frazier, AL AF Banerjee, Smita C. Hay, Jennifer L. Geller, Alan C. Gagne, Joshua J. Frazier, A. Lindsay TI Quitting the "Cancer Tube": a qualitative examination of the process of indoor tanning cessation SO TRANSLATIONAL BEHAVIORAL MEDICINE LA English DT Article DE Health belief model; Indoor tanning; Tanning cessation; Tanning quitting; Qualitative research ID APPEARANCE-FOCUSED INTERVENTION; PREVENT SKIN-CANCER; MALIGNANT-MELANOMA; COLLEGE-STUDENTS; SUNBED USE; RISK; EXPOSURE; BEHAVIOR; HEALTH; METAANALYSIS AB This study examined health belief model (HBM) relevant constructs in the context of indoor tanning cessation. Telephone interviews were conducted between December 2011 and April 2012 with participants drawn from the Growing Up Today Study (GUTS) population, specifically, former tanning bed users (N= 14, all females; mean age, 25.65 years) who reported frequent use in 2007, but had quit by 2010. Participants identified important motivations for quitting including health and financial reasons and the central role of family and friends in providing encouragement for indoor tanning cessation. However, participants also noted substantial barriers to maintaining indoor tanning quitting (e.g., social pressures to look good, tanning salon incentives). Participants' experience of withdrawal highlighted psychological factors more often than physical factors; some were open to resuming use in the future. The findings will be useful in intervention development to encourage cessation, the strengthening of policies to regulate the indoor tanning industry, as well as public health messaging to raise awareness of this prevalent, easily accessible cancer risk behavior. C1 [Banerjee, Smita C.; Hay, Jennifer L.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA. [Geller, Alan C.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Gagne, Joshua J.] Dana Farber Canc Inst, Survey & Data Management Core, Boston, MA 02115 USA. [Frazier, A. Lindsay] Dana Farber Childrens Canc Care, Pediat, Boston, MA USA. RP Banerjee, SC (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 641 Lexington Ave,7th Floor, New York, NY 10022 USA. EM banerjes@mskcc.org FU National Cancer Institute Specialized Programs of Research Excellence (SPORE) in Skin Cancer FX This work was supported by the National Cancer Institute Specialized Programs of Research Excellence (SPORE) in Skin Cancer (Thomas Kupper PI, Brigham and Women's Hospital). NR 41 TC 4 Z9 4 U1 1 U2 5 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1869-6716 EI 1613-9860 J9 TRANSL BEHAV MED JI Transl. Behav. Med. PD JUN PY 2014 VL 4 IS 2 BP 209 EP 219 DI 10.1007/s13142-014-0257-0 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CL2PL UT WOS:000356786400012 PM 24904705 ER PT J AU Liao, KP Diogo, D Cui, J Cai, TX Okada, Y Gainer, VS Murphy, SN Gupta, N Mirel, D Ananthakrishnan, AN Szolovits, P Shaw, SY Raychaudhuri, S Churchill, S Kohane, I Karlson, EW Plenge, RM AF Liao, Katherine P. Diogo, Dorothee Cui, Jing Cai, Tianxi Okada, Yukinori Gainer, Vivian S. Murphy, Shawn N. Gupta, Namrata Mirel, Daniel Ananthakrishnan, Ashwin N. Szolovits, Peter Shaw, Stanley Y. Raychaudhuri, Soumya Churchill, Susanne Kohane, Isaac Karlson, Elizabeth W. Plenge, Robert M. TI Association between low density lipoprotein and rheumatoid arthritis genetic factors with low density lipoprotein levels in rheumatoid arthritis and non-rheumatoid arthritis controls SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID GENOME-WIDE ASSOCIATION; LIPID-LEVELS; COMMON VARIANTS; RISK; LOCI; DISEASE; ATHEROSCLEROSIS; INFLAMMATION; CHOLESTEROL; CONTRIBUTE AB Objectives While genetic determinants of low density lipoprotein (LDL) cholesterol levels are well characterised in the general population, they are understudied in rheumatoid arthritis (RA). Our objective was to determine the association of established LDL and RA genetic alleles with LDL levels in RA cases compared with non-RA controls. Methods Using data from electronic medical records, we linked validated RA cases and non-RA controls to discarded blood samples. For each individual, we extracted data on: first LDL measurement, age, gender and year of LDL measurement. We genotyped subjects for 11 LDL and 44 non-HLA RA alleles, and calculated RA and LDL genetic risk scores (GRS). We tested the association between each GRS and LDL level using multivariate linear regression models adjusted for age, gender, year of LDL measurement and RA status. Results Among 567 RA cases and 979 controls, 80% were female and mean age at the first LDL measurement was 55 years. RA cases had significantly lower mean LDL levels than controls (117.2 vs 125.6 mg/dl, respectively, p<0.0001). Each unit increase in LDL GRS was associated with 0.8 mg/dl higher LDL levels in both RA cases and controls (p=3.0x10(-7)). Each unit increase in RA GRS was associated with 4.3 mg/dl lower LDL levels in both groups (p=0.01). Conclusions LDL alleles were associated with higher LDL levels in RA. RA alleles were associated with lower LDL levels in both RA cases and controls. As RA cases carry more RA alleles, these findings suggest a genetic basis for epidemiological observations of lower LDL levels in RA. C1 [Liao, Katherine P.; Diogo, Dorothee; Cui, Jing; Okada, Yukinori; Raychaudhuri, Soumya; Karlson, Elizabeth W.; Plenge, Robert M.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Diogo, Dorothee; Okada, Yukinori; Raychaudhuri, Soumya; Plenge, Robert M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Diogo, Dorothee; Okada, Yukinori; Gupta, Namrata; Mirel, Daniel; Plenge, Robert M.] Broad Inst, Med & Populat Genet Program, Cambridge, MA USA. [Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Gainer, Vivian S.; Murphy, Shawn N.; Churchill, Susanne; Kohane, Isaac] Partners Healthcare, Res Comp, Charlestown, MA USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Lab Comp Sci, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Szolovits, Peter] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Raychaudhuri, Soumya] Partners Ctr Personalised Genet Med, Boston, MA USA. [Raychaudhuri, Soumya] Univ Manchester, Fac Med & Human Sci, Manchester, Lancs, England. [Kohane, Isaac] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. RP Liao, KP (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St,PBB B3, Boston, MA 02115 USA. EM kliao@partners.org OI Szolovits, Peter/0000-0001-8411-6403 FU NIH [U54-LM008748, K08-AR060257, K08 AR055688, U01HG0070033, K24-AR052403, R01-AR049880, P60-AR047782, R01-AR057108, R01-AR056768, U01-GM092691, R01-AR059648]; Harold and Duval Bowen Fund; Arthritis Foundation; Burroughs Wellcome Fund FX The Informatics for Integrating Biology and the Bedside project is funded by the NIH grant U54-LM008748. KPL is supported by the NIH K08-AR060257 and the Harold and Duval Bowen Fund; SR by the NIH K08 AR055688, U01HG0070033 and the Arthritis Foundation; and EWK by the NIH K24-AR052403, R01-AR049880 and P60-AR047782, RMP NIH R01-AR057108, R01-AR056768, U01-GM092691, R01-AR059648 and the Career Award for Medical Scientists from the Burroughs Wellcome Fund. NR 27 TC 5 Z9 4 U1 0 U2 1 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 JUN PY 2014 VL 73 IS 6 BP 1170 EP 1175 DI 10.1136/annrheumdis-2012-203202 PG 6 WC Rheumatology SC Rheumatology GA AG4AW UT WOS:000335362100039 PM 23716066 ER PT J AU Lee, J Hwang, YJ Ryu, H Kowall, NW Ryu, H AF Lee, Junghee Hwang, Yu Jin Ryu, Hyun Kowall, Neil W. Ryu, Hoon TI Nucleolar dysfunction in Huntington's disease SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE Huntington's disease; Nucleolus; Upstream binding factor (UBF); rDNA transcription; Acetylation and methylation; Epigenetics ID RIBOSOMAL-RNA GENES; WILD-TYPE HUNTINGTIN; TRANSCRIPTION FACTOR; POLYMERASE-I; HISTONE ACETYLTRANSFERASE; NEUROLOGICAL PHENOTYPE; STRIATAL NEURONS; SPINY NEURONS; MOUSE MODELS; CAG REPEATS AB Huntington's disease (HD) is a fatal genetic disorder characterized by triad clinical symptoms of chorea, emotional distress, and cognitive decline. Genetic mutation in HD is identified by an expansion of CAG repeats coding for glutamine (Q) in exon 1 of the huntingtin (htt) gene. The exact mechanism on how mutant htt leads to the selective loss of medium spiny neurons (MSNs) in the striatum is still unknown. Recent studies suggest that nucleolar stress and dysfunction are linked to the pathogenesis of HD. Alterations of the nucleolar activity and integrity contribute to deregulation of ribosomal DNA (rDNA) transcription in HD pathogenesis. Furthermore, epigenetic modifications in the nucleolus are associated with neuronal damage in HD. In this review, we discuss about how post-translational modifications of upstream binding factor (UBF) are affected by histone acetyltransferase and histone methyltransferase and involved in the transcriptional regulation of rDNA in HD. The understanding of epigenetic modulation of UBF-dependent rDNA transcription in the nucleolus may lead to the identification of novel pathological markers and new therapeutic targets to treat HD. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease. (C) 2013 Elsevier BM. All rights reserved. C1 [Lee, Junghee; Kowall, Neil W.; Ryu, Hoon] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Lee, Junghee; Ryu, Hyun; Kowall, Neil W.; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Hwang, Yu Jin] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, WCU Neurocyt Grp, Seoul 110799, South Korea. [Ryu, Hoon] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neuromed, Seoul, South Korea. RP Ryu, H (reprint author), VA Boston Healthcare Syst, Bldg 1A,Rm 109,150 S Huntington Ave, Boston, MA 02130 USA. EM hoonryu@bu.edu RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIH [NS 067283]; Brain Science Flagship from Korea Institute of Science and Technology [2E24380] FX This study was supported by NIH NS 067283 (H.R) and Brain Science Flagship Grant (2E24380) (H.R.) from Korea Institute of Science and Technology. NR 67 TC 15 Z9 15 U1 0 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 EI 0006-3002 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JUN PY 2014 VL 1842 IS 6 SI SI BP 785 EP 790 DI 10.1016/j.bbadis.2013.09.017 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA AG5AP UT WOS:000335431800006 PM 24184605 ER PT J AU Chen, Y Won, SJ Xu, Y Swanson, RA AF Chen, Y. Won, S. J. Xu, Y. Swanson, R. A. TI Targeting Microglial Activation in Stroke Therapy: Pharmacological Tools and Gender Effects SO CURRENT MEDICINAL CHEMISTRY LA English DT Article DE Brain; corticosteroid; female; HDAC; inflammation; ischemia; minocycline; PARP ID FOCAL CEREBRAL-ISCHEMIA; HISTONE DEACETYLASE INHIBITORS; TUMOR-NECROSIS-FACTOR; GROUP BOX1-INHIBITING MECHANISM; BRAIN-INJURY; RAT-BRAIN; POLY(ADP-RIBOSE) POLYMERASE-1; GENE-EXPRESSION; FACTOR-ALPHA; CELL-DEATH AB Ischemic stroke is caused by critical reductions in blood flow to brain or spinal cord. Microglia are the resident immune cells of the central nervous system, and they respond to stroke by assuming an activated phenotype that releases cytotoxic cytokines, reactive oxygen species, proteases, and other factors. This acute, innate immune response may be teleologically adapted to limit infection, but in stroke this response can exacerbate injury by further damaging or killing nearby neurons and other cell types, and by recruiting infiltration of circulating cytotoxic immune cells. The microglial response requires hours to days to fully develop, and this time interval presents a clinically accessible time window for initiating therapy. Because of redundancy in cytotoxic microglial responses, the most effective therapeutic approach may be to target the global gene expression changes involved in microglial activation. Several classes of drugs can do this, including histone deacetylase inhibitors, minocycline and other PARP inhibitors, corticosteroids, and inhibitors of TNF alpha and scavenger receptor signaling. Here we review the pre-clinical studies in which these drugs have been used to suppress microglial activation after stroke. We also review recent advances in the understanding of sex differences in the CNS inflammatory response, as these differences are likely to influence the efficacy of drugs targeting post-stroke brain inflammation. C1 [Chen, Y.; Xu, Y.] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Neurol, Nanjing 210008, Jiangsu, Peoples R China. [Chen, Y.; Won, S. J.; Swanson, R. A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Chen, Y.; Won, S. J.; Swanson, R. A.] San Francisco VA Med Ctr, Neurol Serv, San Francisco, CA 94121 USA. RP Swanson, RA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM raymond.swanson@ucsf.edu OI Swanson, Raymond/0000-0002-3664-5359 FU Chinese Research Scholarship Council; U.S. National Institutes of Health [NS041421]; U.S. Department of Veterans Affairs FX This work was supported by the Chinese Research Scholarship Council (Y.C.) the U.S. National Institutes of Health (grant # NS041421, R.A.S.), and the U.S. Department of Veterans Affairs. NR 132 TC 18 Z9 18 U1 0 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 EI 1875-533X J9 CURR MED CHEM JI Curr. Med. Chem. PD JUN PY 2014 VL 21 IS 19 BP 2146 EP 2155 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AG4MF UT WOS:000335393300005 PM 24372213 ER PT J AU Fitten, LJ Ortiz, F Fairbanks, L Bartzokis, G Lu, P Klein, E Coppola, G Ringman, J AF Fitten, L. Jaime Ortiz, Freddy Fairbanks, Lynn Bartzokis, George Lu, Po Klein, Eric Coppola, Giovanni Ringman, John TI Younger age of dementia diagnosis in a Hispanic population in southern California SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE diagnosis; Hispanic; onset; Alzheimer's disease; Latino; age; dementia; vascular dementia; APOE genotype; diagnosis ID APOLIPOPROTEIN-E EPSILON-4; MINI-MENTAL-STATE; OLDER MEXICAN-AMERICANS; ALZHEIMERS-DISEASE; DIABETES-MELLITUS; AFRICAN-AMERICANS; CARIBBEAN HISPANICS; NORTHERN MANHATTAN; RISK; ONSET AB Objective Prior studies of US Hispanics, largely performed on the East Coast, have found a younger age of dementia onset than in White non-Hispanics. We performed a cross-sectional study to examine clinical and sociodemographic variables associated with age of dementia diagnosis in older Hispanics and White, non-Hispanics in southern California. Methods Two hundred ninety (110 Hispanic and 180 White non-Hispanic) community dwelling, cognitively symptomatic subjects, aged 50 years and older, were assessed and diagnosed with probable Alzheimer's disease or probable vascular dementia. Apolipoprotein E (APOE) genotype was assessed in a subset of cases. Analysis of variance and multiple stepwise linear regression were used to assess main effects and interactions of ethnicity with dementia severity (indexed by mini mental state examination scores) and other sociodemographic and clinical variables on age of dementia diagnosis. Results Hispanics were younger by an average of 4 years at the time of diagnosis, regardless of dementia subtype, despite a similar prevalence of the APOE epsilon 4 genotype. The earlier age at diagnosis for Hispanics was not explained by gender, dementia severity, years of education, history of hypercholesterolemia, hypertension, or diabetes. Only ethnicity was significantly associated with age of onset. Conclusions These findings confirm that US Hispanics living in the southwestern USA tend to be younger at the time of dementia diagnosis than their White non-Hispanic counterparts. As this is not explained by the presence of the APOE epsilon 4 genotype, further studies should explore other cultural, medical, or genetic risk factors influencing the age of dementia onset in this population. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Fitten, L. Jaime; Ortiz, Freddy; Fairbanks, Lynn; Bartzokis, George; Lu, Po; Coppola, Giovanni; Ringman, John] Univ Calif Los Angeles, David Geffen Sch Med, Easton Ctr Alzheimer Dis Res, Los Angeles, CA 90095 USA. [Fitten, L. Jaime; Ortiz, Freddy] US Dept Vet Affairs, Greater Los Angeles Vet Affairs Healthcare Syst, Sepulveda Ambulatory Care Ctr, Los Angeles, CA USA. [Fitten, L. Jaime; Ortiz, Freddy] Univ Calif Los Angeles, Med Ctr, Dept Psychiat Olive View, Los Angeles, CA 90024 USA. [Fitten, L. Jaime; Fairbanks, Lynn; Bartzokis, George; Lu, Po; Klein, Eric; Coppola, Giovanni] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Ortiz, Freddy; Lu, Po; Ringman, John] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Bartzokis, George] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. [Bartzokis, George] Greater Los Angeles VA Healthcare Syst, West Los Angeles, CA USA. RP Fitten, LJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Easton Ctr Alzheimer Dis Res, Los Angeles, CA 90095 USA. EM jfitten@ucla.edu FU NIA-UCLA ADRC [P50 AG16570]; State of California Alzheimer's Disease Center at UCLA, the Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarker Development; Olive View-UCLA Medical Center, Sylmar, CA, USA; VA Greater Los Angeles Healthcare System, Sepulveda, CA, USA FX This study was supported by funding from the NIA-UCLA ADRC (P50 AG16570); by the State of California Alzheimer's Disease Center at UCLA, the Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarker Development; by the Olive View-UCLA Medical Center, Sylmar, CA, USA; and by the VA Greater Los Angeles Healthcare System, Sepulveda, CA, USA. NR 37 TC 6 Z9 6 U1 2 U2 7 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 JUN PY 2014 VL 29 IS 6 BP 586 EP 593 DI 10.1002/gps.4040 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA AG2ND UT WOS:000335252300005 PM 24478258 ER PT J AU Raskind, MA Wang, LY AF Raskind, Murray A. Wang, Lucy Y. TI Antipsychotic drugs for psychosis and agitation in dementia: efficacy, safety, and a possible noradrenergic mechanism of action SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Editorial Material ID PLACEBO-CONTROLLED-TRIAL; NURSING-HOME RESIDENTS; ALZHEIMERS-DISEASE; DOUBLE-BLIND; LOCUS-COERULEUS; BEHAVIORAL DISTURBANCES; SENILE DEMENTIA; CLINICAL-TRIAL; TYROSINE-HYDROXYLASE; COMPENSATORY CHANGES AB The first patient described by Alzheimer in 1907 had both progressive cognitive deterioration and prominent comorbid signs and symptoms of psychosis and agitation (Alzheimer, 1907, 1987). In this editorial, we use "psychosis" to denote delusions and hallucinations and "agitation" to denote irritability, aggression, pressured motor activity, and active resistance to necessary care. Although advances have been made in the treatment of these non-cognitive symptoms, these psychosis and agitation symptoms continued to be burdensome and costly for dementia patients, caregivers, and society. Among the pharmacologic treatments available for psychosis and agitation, antipsychotic drugs are the drug class most consistently demonstrated effective for psychosis and agitation in dementia (Lyketsos et al., 2006; APA Work Group on Alzheimer's Disease and Other Dementias et al., 2007). These are widely prescribed for these behavioral problems, but their use remains controversial and their mechanism of action unclear. C1 [Raskind, Murray A.] Univ Washington, Vet Affairs Northwest Network VISN 20, Mental Illness Res Educ & Clin Ctr, Mental Hlth Serv,VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Raskind, MA (reprint author), Univ Washington, Vet Affairs Northwest Network VISN 20, Mental Illness Res Educ & Clin Ctr, Mental Hlth Serv,VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM murray.raskind@va.gov NR 45 TC 1 Z9 1 U1 1 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD JUN PY 2014 VL 26 IS 6 BP 879 EP 883 AR PII S1041610214000477 DI 10.1017/S1041610214000477 PG 5 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA AG4RK UT WOS:000335407700001 PM 24703502 ER PT J AU Vatsavayi, AVV Kofler, J DeMichele-Sweet, MAA Murray, PS Lopez, OL Sweet, RA AF Vatsavayi, Anil Varma V. Kofler, Julia DeMichele-Sweet, Mary Ann A. Murray, Patrick S. Lopez, Oscar L. Sweet, Robert A. TI TAR DNA-binding protein 43 pathology in Alzheimer's disease with psychosis SO INTERNATIONAL PSYCHOGERIATRICS LA English DT Article DE Alzheimer's disease; TDP-43; psychosis ID FRONTOTEMPORAL LOBAR DEGENERATION; NEUROPATHOLOGIC ASSESSMENT; TDP-43 IMMUNOREACTIVITY; HIPPOCAMPAL SCLEROSIS; RISK-FACTORS; DELUSIONS; SYMPTOMS; PHENOTYPE; DEMENTIA; BEHAVIOR AB Background: TAR DNA-binding protein 43 (TDP-43) has been identified as a major disease protein in frontotemporal lobar degeneration. More recently, TDP-43 proteinopathy has also been observed in Alzheimer's disease (AD) with a characteristic distribution of TDP-43 predominantly in the mesial temporal lobe, and to a lesser degree in the neocortical areas. AD subjects with psychotic symptoms (AD+P) represent a subgroup characterized by greater impairment of frontal cortex-dependent cognitive functions and more severe frontal cortical neuropathology. The aim of this study is to determine whether there is an association between TDP-43 pathology and AD+P. We hypothesized that TDP-43 pathology would be more frequent in AD+P than in AD without psychosis. Methods: We studied the presence and distribution of TDP-43 pathology by immunohistochemistry in the dentate gyrus (DG) and prefrontal cortex (FC) of postmortem brain specimens from 68 subjects with a primary neuropathologic diagnosis of AD as determined by the Neuropathology Core of the University of Pittsburgh Alzheimer's Disease Research Center. Results: Forty-five (66%) subjects were classified as AD+P. Fourteen (20.6%) subjects had TDP-43 pathology in DG, eight (11.8%) had TDP-43 pathology in FC, and six (8.8%) had TDP-43 pathology in both regions. TDP-43 in DG was not significantly associated with AD+P. However, TDP-43 in FC demonstrated a trend toward reduced likelihood of psychosis (p = 0.068). TDP-43 pathology in DG, but not FC, was significantly associated with greater age at death and longer duration of illness. Conclusions: Our findings indicate that there was no association between concomitant TDP-43 pathology in DG or FC and AD+P. C1 [Vatsavayi, Anil Varma V.; Murray, Patrick S.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Translat Neurosci Program, Pittsburgh, PA USA. [Vatsavayi, Anil Varma V.; DeMichele-Sweet, Mary Ann A.; Murray, Patrick S.; Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Vatsavayi, Anil Varma V.; Murray, Patrick S.; Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. [Lopez, Oscar L.; Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Kofler, Julia] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Biomed Sci Tower,W1645 3811,OHara St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu OI Murray, Patrick/0000-0002-6525-2888 FU National Institute of Aging [AG05133, AG027224]; VA Pittsburgh Healthcare System (VAPHS) [BX000452] FX This work was supported in part by the National Institute of Aging grants AG05133 (OLL) and AG027224 (RAS), and the VA Pittsburgh Healthcare System (VAPHS) grant BX000452 (RAS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, the Department of Veterans Affairs, or the United States Government. NR 40 TC 3 Z9 3 U1 2 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1041-6102 EI 1741-203X J9 INT PSYCHOGERIATR JI Int. Psychogeriatr. PD JUN PY 2014 VL 26 IS 6 BP 987 EP 994 DI 10.1017/S1041610214000246 PG 8 WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry; Psychology SC Psychology; Geriatrics & Gerontology; Psychiatry GA AG4RK UT WOS:000335407700013 PM 24588894 ER PT J AU Abuelo, CE Levinson, KL Salmeron, J Sologuren, CV Fernandez, MJV Belinson, JL AF Abuelo, Carolina E. Levinson, Kimberly L. Salmeron, Jorge Vallejos Sologuren, Carlos Vallejos Fernandez, Maria Jose Belinson, Jerome L. TI The Peru Cervical Cancer Screening Study (PERCAPS): The Design and Implementation of a Mother/Daughter Screen, Treat, and Vaccinate Program in the Peruvian Jungle SO JOURNAL OF COMMUNITY HEALTH LA English DT Article DE Human papillomavirus; Cervical cancer screening; Community based participatory; Research techniques; Peru ID SELF-COLLECTED SAMPLES; HUMAN-PAPILLOMAVIRUS; HPV; ACCEPTABILITY; CYTOLOGY; PART AB Peru struggles to prevent cervical cancer (CC). In the jungle, prevention programs suffer from significant barriers although technology exists to detect CC precursors. This study used community based participatory research (CBPR) methods to overcome barriers. The objective was to evaluate the utility of CBPR techniques in a mother-child screen/treat and vaccinate program for CC prevention in the Peruvian jungle. The CC prevention program used self-sampling for human papillomavirus (HPV) for screening, cryotherapy for treatment and the HPV vaccine Gardasil for vaccination. Community health leaders (HL) from around Iquitos participated in a two half day educational course. The HLs then decided how to implement interventions in their villages or urban sectors. The success of the program was measured by: (1) ability of the HLs to determine an implementation plan, (2) proper use of research forms, (3) participation and retention rates, and (4) participants' satisfaction. HLs successfully registered 320 women at soup kitchens, schools, and health posts. Screening, treatment, and vaccination were successfully carried out using forms for registration, consent, and results with minimum error. In the screen/treat intervention 100 % of participants gave an HPV sample and 99.7 % reported high satisfaction; 81 % of HPV + women were treated, and 57 % returned for 6-month followup. Vaccine intervention: 98 % of girls received the 1st vaccine, 88 % of those received the 2nd, and 65 % the 3rd. CBPR techniques successfully helped implement a screen/treat and vaccinate CC prevention program around Iquitos, Peru. These techniques may be appropriate for large-scale preventive health-care interventions. C1 [Abuelo, Carolina E.] Massachusetts Gen Hosp, Charlestown HealthCare Ctr, Charlestown, MA 02445 USA. [Levinson, Kimberly L.] Cleveland Clin, Womens Hlth Inst, Cleveland, OH 44106 USA. [Salmeron, Jorge] Inst Mexicano Seguro Social, Cuernavaca, Morelos, Mexico. [Vallejos Sologuren, Carlos; Vallejos Fernandez, Maria Jose] Oncosalud, Lima, Peru. [Belinson, Jerome L.] Prevent Oncol Int, Cleveland, OH USA. RP Abuelo, CE (reprint author), Massachusetts Gen Hosp, Charlestown HealthCare Ctr, 73 High St, Charlestown, MA 02445 USA. EM cabuelo@partners.org FU FIC NIH HHS [R24 TW007988] NR 17 TC 4 Z9 4 U1 7 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0094-5145 EI 1573-3610 J9 J COMMUN HEALTH JI J. Community Health PD JUN PY 2014 VL 39 IS 3 BP 409 EP 415 DI 10.1007/s10900-013-9786-6 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA AG4LY UT WOS:000335392600001 PM 24276617 ER PT J AU Peters, AT Peckham, AD Stange, JP Sylvia, LG Hansen, NS Salcedo, S Rauch, SL Nierenberg, AA Dougherty, DD Deckersbach, T AF Peters, Amy T. Peckham, Andrew D. Stange, Jonathan P. Sylvia, Louisa G. Hansen, Natasha S. Salcedo, Stephanie Rauch, Scott L. Nierenberg, Andrew A. Dougherty, Darin D. Deckersbach, Thilo TI Correlates of real world executive dysfunction in bipolar I disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Executive function; Bipolar; Cognition ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; QUALITY-OF-LIFE; NEUROCOGNITIVE IMPAIRMENT; FUNCTIONAL IMPAIRMENT; COGNITIVE REHABILITATION; EMPLOYMENT STATUS; EUTHYMIC PATIENTS; RATING-SCALE; DSM-IV; SCHIZOPHRENIA AB Background: Bipolar disorder is characterized by impairments in cognitive functioning, both during acute mood episodes and periods of euthymia, which interfere with functioning. Cognitive functioning is typically assessed using laboratory-based tests, which may not capture how cognitive dysfunction is experienced in real-life settings. Little is known about the specific illness characteristics of bipolar disorder that contribute to cognitive dysfunction in everyday life. Methods: Participants met DSM-IV criteria for bipolar I disorder (n = 68) in a depressed or euthymic state. Everyday executive functioning was evaluated using the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Frontal Systems Behavior Rating Scale (FrSBe). Participants completed clinician rated measures of mood state (Hamilton Depression Rating Scale, Young Mania Rating Scale), prior illness course and co-morbidities (Mini International Neuropsychiatric Interview), as well as self-report measures of psychotropic medication use and medical co-morbidity. Results: Individuals in this study reported significant impairment in every domain of executive functioning. These deficits were associated with a multitude of illness factors, some directly impacted by mood symptoms and others shaped by illness chronicity, psychiatric comorbidity, medical co-morbidity, and medication use. Discussion: Executive functioning problems observed in everyday functioning in bipolar disorder are not entirely mood-state dependent. Cognitive rehabilitation for executive dysfunction should be considered an important adjunctive treatment for many individuals with bipolar disorder. (C) 2014 Elsevier Ltd. All rights reserved. C1 [Peters, Amy T.] Univ Illinois, Chicago, IL USA. [Peckham, Andrew D.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Stange, Jonathan P.] Temple Univ, Philadelphia, PA 19122 USA. [Sylvia, Louisa G.; Hansen, Natasha S.; Salcedo, Stephanie; Nierenberg, Andrew A.; Dougherty, Darin D.; Deckersbach, Thilo] Massachusetts Gen Hosp, Boston, MA USA. [Sylvia, Louisa G.; Rauch, Scott L.; Nierenberg, Andrew A.; Dougherty, Darin D.; Deckersbach, Thilo] Harvard Univ, Sch Med, Boston, MA USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149-2628,Bldg 149,13th St,2nd Floor, Charlestown, MA 02129 USA. EM tdeckersbach@partners.org FU K-23 NIMH Career Award [1K23MH074895-01A2] FX This work was supported by a K-23 NIMH Career Award 1K23MH074895-01A2 to Thilo Deckersbach, PhD. NR 53 TC 9 Z9 9 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD JUN PY 2014 VL 53 BP 87 EP 93 DI 10.1016/j.jpsychires.2014.02.018 PG 7 WC Psychiatry SC Psychiatry GA AG0KK UT WOS:000335104200013 PM 24655587 ER PT J AU Carl, JR Fairholme, CP Gallagher, MW Thompson-Hollands, J Barlow, DH AF Carl, Jenna R. Fairholme, Christopher P. Gallagher, Matthew W. Thompson-Hollands, Johanna Barlow, David H. TI The Effects of Anxiety and Depressive Symptoms on Daily Positive Emotion Regulation SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE Positive emotion; Anxiety; Depression; Emotion regulation; Daily diary ID IMPAIRMENT SCALE OASIS; INDIVIDUAL-DIFFERENCES; NEGATIVE EMOTIONS; MAJOR DEPRESSION; DAILY-LIFE; DISORDER; REACTIVITY; EXPERIENCE; VALIDATION; EVENTS AB Individuals with anxiety and depressive symptoms exhibit disturbances in positive emotion regulation, which may hinder full recovery. By comparison, individuals with strong beliefs regarding their capacity to "savor" or maintain positive emotions (i.e., savoring beliefs) display more adaptive positive emotion regulation. The present daily diary study explores three momentary processes involved in positive emotion regulation, namely positive emotion reactivity, regulatory goals, and regulatory effectiveness, and examines the comparative effects of baseline anxiety and depressive symptoms versus savoring beliefs on such processes in real-life contexts. A sample of 164 nonclinical undergraduates provided baseline measures of anxiety and depressive symptom severity and savoring beliefs prior to completing 14 daily assessments of positive emotions and emotion regulatory responses to daily positive events. Results indicated that higher baseline anxiety and depressive symptom severity were associated with decreased positive emotion reactivity and increased down-regulation of positive emotions; higher baseline savoring beliefs were associated with increased positive emotion reactivity, decreased down-regulation and increased up-regulation of positive emotions. Potential clinical implications are discussed. C1 [Carl, Jenna R.; Thompson-Hollands, Johanna; Barlow, David H.] Boston Univ, Dept Psychol, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Fairholme, Christopher P.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Gallagher, Matthew W.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD,Natl Ctr PTSD 116B 2, Boston, MA 02130 USA. RP Carl, JR (reprint author), Boston Univ, Dept Psychol, Ctr Anxiety & Related Disorders, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM jcarl@bu.edu NR 58 TC 0 Z9 0 U1 9 U2 39 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 EI 1573-3505 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD JUN PY 2014 VL 36 IS 2 BP 224 EP 236 DI 10.1007/s10862-013-9387-9 PG 13 WC Psychology, Clinical SC Psychology GA AG3KA UT WOS:000335313600005 ER PT J AU Minzenberg, MJ Gomes, GC Yoon, JH Watrous, AJ Geng, J Firl, AJ Carter, CS AF Minzenberg, Michael J. Gomes, Glenn C. Yoon, Jong H. Watrous, Andrew J. Geng, Joy Firl, Alana J. Carter, Cameron S. TI Modafinil augments oscillatory power in middle frequencies during rule selection SO PSYCHOPHYSIOLOGY LA English DT Article DE Prefrontal cortex; Cognitive control; Oscillations; Theta; Modafinil; Rule selection ID INDEPENDENT COMPONENT ANALYSIS; INTERNEURON DIVERSITY SERIES; PREFRONTAL CORTEX; LOCUS-COERULEUS; WORKING-MEMORY; THETA-OSCILLATIONS; COGNITIVE CONTROL; 1ST-EPISODE SCHIZOPHRENIA; PHASE SYNCHRONIZATION; NETWORK OSCILLATIONS AB Control-related cognitive processes are associated with cortical oscillations and modulated by catecholamine neurotransmitters. It remains unclear how catecholamine systems modulate control-related oscillations. We tested modafinil effects on rule-related 4-30 Hz oscillations, with double-blind, placebo-controlled (within-subjects) testing of 22 healthy adults, using EEG during cognitive control task performance. EEG data underwent time-frequency decomposition with Morlet wavelets to determine power of 4-30 Hz oscillations. Modafinil enhanced oscillatory power associated with high-control rule selection in theta, alpha, and beta ranges, with a frontotemporal topography and minimal effects during rule maintenance. Augmentation of catecholamine signaling enhances middle-frequency cortical oscillatory power associated with rule selection, which may subserve diverse subcomponent processes in proactive cognitive control. C1 [Minzenberg, Michael J.] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Minzenberg, Michael J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Gomes, Glenn C.; Carter, Cameron S.] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA. [Yoon, Jong H.] Stanford Univ, Sch Med, Dept Psychiat, Palo Alto, CA 94304 USA. [Yoon, Jong H.] Palo Alto Vet Affairs Med Ctr, Palo Alto, CA USA. [Watrous, Andrew J.; Geng, Joy; Carter, Cameron S.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Firl, Alana J.] Univ Calif Berkeley, Program Vis Neurosci, Berkeley, CA 94720 USA. RP Minzenberg, MJ (reprint author), 116C San Francisco Vet Affairs Med Ctr, Outpatient Mental Hlth Serv, 4150 Clement St, San Francisco, CA 94121 USA. EM Michael.minzenberg@ucsf.edu FU Doris Duke Charitable Foundation; NARSAD (Brain and Behavior Foundation); National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [UL1 RR024146]; NIH Roadmap for Medical Research FX This work was supported by a Clinical Scientist Development Award from the Doris Duke Charitable Foundation and a Young Investigator award from NARSAD (Brain and Behavior Foundation) to MJM. This publication was also made possible by Grant Number UL1 RR024146 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. The authors would like to acknowledge the assistance of Janeth Nunez del Prado, Jenny Yen, and Dennis Thompson in the conduct and analysis of the study. NR 84 TC 4 Z9 4 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JUN PY 2014 VL 51 IS 6 BP 510 EP 519 DI 10.1111/psyp.12201 PG 10 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA AG1SL UT WOS:000335196300002 PM 24611660 ER PT J AU Leung, CM Stone, WS Lee, EHM Seidman, LJ Chen, EYH AF Leung, Chung-Ming Stone, William S. Lee, Edwin Ho-Ming Seidman, Larry J. Chen, Eric Yu-Hai TI Impaired facilitation of self-control cognition by glucose in patients with schizophrenia: A randomized controlled study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Nutrition-based intervention; Cognition; Willpower; Impulse control ID BLOOD-GLUCOSE; INSULIN-RESISTANCE; LIMITED RESOURCE; ALZHEIMER-TYPE; MEMORY; DEPLETION; ENERGY; SCALE; IMPULSIVITY; PERFORMANCE AB Objective: Studies in healthy individuals show that exerting self-control consumes cognitive resources, which reduces subsequent self-control performance. Restoring the availability of blood glucose eliminates this impairment. Patients with schizophrenia are found to have self-regulatory dysfunctions. This study aims to investigate whether patient's (a) glucose facilitation effects will be impaired, and (b) will have exaggerated depletion in a self-control task. Method: 40 patients with schizophrenia-spectrum disorders and 40 normal controls were recruited. A two drinks (glucose vs. placebo) x two depleting phases (self-control depleted vs. non-depleted) between groups design was used. We examined the blood glucose levels before and after the selfcontrol depletion phase and the subsequent performances in two self-control tasks (handgrip and Stroop tests) after the drink condition. Results: The four groups (depleting x glucose, depleting x placebo, non-depleting x glucose and nondepleting x placebo) of both patients and normal controls were comparable on a number of characteristics. The change in blood glucose level in the depleting group was significantly different from those in the non-depleting group. Two x two between-subjects ANOVAs were carried out to test the performances in the handgrip and Stroop tasks. Significant interactions were found in healthy controls regarding both tasks. However, a significant interaction was only found in patients regarding the handgrip task but not the Stroop task. Conclusions: This study demonstrated an abnormal glucose facilitation effect in patients during a cognitive self-control task but not during a physical self-control task. The findings also suggested for the first time that a self-control depletion effect is intact in patients with schizophrenia. (C) 2014 Elsevier B. V. All rights reserved. C1 [Leung, Chung-Ming; Lee, Edwin Ho-Ming; Chen, Eric Yu-Hai] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China. [Stone, William S.; Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Dept Psychiat,Div Publ Psychiat,Med Sch, Boston, MA 02115 USA. [Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Chen, Eric Yu-Hai] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. RP Chen, EYH (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Psychiat, 102 Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China. EM eyhchen@hku.hk FU Psychiatry Department, University of Hong Kong, Hong Kong FX The project was funded by the internal funding of the Psychiatry Department, University of Hong Kong, Hong Kong. NR 62 TC 3 Z9 3 U1 2 U2 13 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 JUN PY 2014 VL 156 IS 1 BP 38 EP 45 DI 10.1016/j.schres.2014.03.010 PG 8 WC Psychiatry SC Psychiatry GA AG5IF UT WOS:000335452000006 PM 24731620 ER PT J AU Yeo, RA Gangestad, SW Walton, E Ehrlich, S Pommy, J Turner, JA Liu, JY Mayer, AR Schulz, SC Ho, BC Bustillo, JR Wassink, TH Sponheim, SR Morrow, EM Calhoun, VD AF Yeo, Ronald A. Gangestad, Steven W. Walton, Esther Ehrlich, Stefan Pommy, Jessica Turner, Jessica A. Liu, Jingyu Mayer, Andrew R. Schulz, S. Charles Ho, Beng-Choon Bustillo, Juan R. Wassink, Thomas H. Sponheim, Scott R. Morrow, Eric M. Calhoun, Vince D. TI Genetic influences on cognitive endophenotypes in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Genetics; Executive function; Mutation; Cognitive; Endophenotype ID COPY NUMBER VARIATION; INTELLIGENCE; EVOLUTION; DEFICIT; DISEASE; SIZE AB Background: Cognitive deficits are prominent in schizophrenia and represent promising endophenotypes for genetic research. Methods: The current study investigated the importance of two conceptually distinct genetic aggregates, one based on copy number variations (uncommon deletion burden), and one based on single nucleotide polymorphisms identified in recent risk studies (genetic risk score). The impact of these genetic factors, and their interaction, was examined on cognitive endophenotypes defined by principal component analysis (PCA) in a multi-center sample of 50 patients with schizophrenia and 86 controls. PCA was used to identify three different types of executive function (EF: planning, fluency, and inhibition), and in separate analyses, a measure general cognitive ability (GCA). Results: Cognitive deficits were prominent among individuals with schizophrenia, but no group differences were evident for either genetic factor. Among patients the deletion burden measures predicted cognitive deficits across the three EF components and GCA. Further, an interaction was noted between the two genetic factors for both EF and GCA and the observed patterns of interaction suggested antagonistic epistasis. In general, the set of genetic interactions examined predicted a substantial portion of variance in these cognitive endophenotypes. Limitations: Though adequately powered, our sample size is small for a genetic study. Conclusions: These results draw attention to genetic interactions and the possibility that genetic influences on cognition differ in patients and controls. (C) 2014 Elsevier B. V. All rights reserved. C1 [Yeo, Ronald A.; Gangestad, Steven W.; Pommy, Jessica] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. [Yeo, Ronald A.; Turner, Jessica A.; Liu, Jingyu; Mayer, Andrew R.; Bustillo, Juan R.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM USA. [Walton, Esther; Ehrlich, Stefan] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Walton, Esther; Ehrlich, Stefan] Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Dresden, Germany. [Walton, Esther; Ehrlich, Stefan] Tech Univ Dresden, Dresden, Germany. [Ehrlich, Stefan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Turner, Jessica A.] Georgia State Univ, Inst Neurosci, Atlanta, GA 30303 USA. [Liu, Jingyu; Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Schulz, S. Charles; Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Ho, Beng-Choon; Wassink, Thomas H.] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Bustillo, Juan R.] Univ New Mexico, Dept Psychiat, Albuquerque, NM 87131 USA. [Sponheim, Scott R.] Minneapolis Vet Adm Hlth Care Syst, Minneapolis, MN USA. [Morrow, Eric M.] Brown Univ, Mol Med Lab, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. RP Yeo, RA (reprint author), Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. EM ryeo@unm.edu RI Ho, Beng-Choon/D-6959-2011; Turner, Jessica/H-7282-2015; OI Ho, Beng-Choon/0000-0003-3976-1555; Turner, Jessica/0000-0003-0076-8434; Ehrlich, Stefan/0000-0003-2132-4445; Gangestad, Steven/0000-0002-8879-4348; Walton, Esther/0000-0002-0935-2200; Liu, Jingyu/0000-0002-1724-7523 FU U.S. Department of Energy [DE-FG02-08ER64581]; National Institutes of Health [5P20RR 021938, 1RC1MH089257, R01EB005846] FX This work was supported by grants from the U.S. Department of Energy under Award Number DE-FG02-08ER64581, and the National Institutes of Health (grants 5P20RR 021938, 1RC1MH089257 and R01EB005846). NR 30 TC 6 Z9 6 U1 0 U2 5 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 JUN PY 2014 VL 156 IS 1 BP 71 EP 75 DI 10.1016/j.schres.2014.03.022 PG 5 WC Psychiatry SC Psychiatry GA AG5IF UT WOS:000335452000013 PM 24768440 ER PT J AU Terasaki, Y Liu, Y Hayakawa, K Pham, LD Lo, EH Ji, X Arai, K AF Terasaki, Y. Liu, Y. Hayakawa, K. Pham, L. D. Lo, E. H. Ji, X. Arai, K. TI Mechanisms of Neurovascular Dysfunction in Acute Ischemic Brain SO CURRENT MEDICINAL CHEMISTRY LA English DT Article DE Cell-cell interaction; extracellular vesicles; neuronal cell death; neuroprotection; neurovascular unit; stroke ID NEURONAL CELL-DEATH; CIRCULATING ENDOTHELIAL MICROPARTICLES; FOCAL CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; MATRIX METALLOPROTEINASES; NMDA RECEPTOR; OLIGODENDROCYTE DIFFERENTIATION; NEUROTROPHIC FACTOR; GLUTAMATE RELEASE; SECRETE EXOSOMES AB The neurovascular unit is now well accepted as a conceptual framework for investigating the mechanisms of ischemic stroke. From a molecular and cellular perspective, three broad mechanisms may underlie stroke pathophysiology-excitotoxicity, oxidative stress and inflammation. To date, however, most investigations of these basic mechanisms have focused on neuronal responses. In this mini-review, we ask whether these mechanisms of excitotoxicity, oxidative stress and inflammation can also be examined in terms of non-neuronal interactions in the neurovascular unit, including the release of extracellular vesicles for cell-cell signaling. C1 [Liu, Y.; Ji, X.] Capital Med Univ, Amer Massachusetts Gen Hosp, Joint Inst Neurosci, China Xuan Wu Hosp,Xuan Wu Hosp, Beijing, Peoples R China. [Liu, Y.; Ji, X.] Geriatr Med Res Ctr, Beijing, Peoples R China. [Terasaki, Y.; Liu, Y.; Hayakawa, K.; Pham, L. D.; Lo, E. H.; Ji, X.; Arai, K.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Terasaki, Y.; Liu, Y.; Hayakawa, K.; Pham, L. D.; Lo, E. H.; Ji, X.; Arai, K.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Terasaki, Y.; Liu, Y.; Hayakawa, K.; Pham, L. D.; Lo, E. H.; Ji, X.; Arai, K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Ji, X (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. EM jixm@ccmu.edu.cn; karai@partners.org FU National Institutes of Health; SUMITOMO Life Social Welfare Service Foundation; National Natural Science Foundation of China [81200915]; Beijing Natural Science Foundation; China National Basic Research 973 Program FX Supported in part by grants from the National Institutes of Health, the SUMITOMO Life Social Welfare Service Foundation, the National Natural Science Foundation of China (Grant No. 81200915), the Beijing Natural Science Foundation, and the China National Basic Research 973 Program. NR 123 TC 13 Z9 13 U1 1 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 EI 1875-533X J9 CURR MED CHEM JI Curr. Med. Chem. PD JUN PY 2014 VL 21 IS 18 BP 2035 EP 2042 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AF6UM UT WOS:000334850100003 PM 24372202 ER PT J AU Kim, JY Kawabori, M Yenari, MA AF Kim, J. Y. Kawabori, M. Yenari, M. A. TI Innate Inflammatory Responses in Stroke: Mechanisms and Potential Therapeutic Targets SO CURRENT MEDICINAL CHEMISTRY LA English DT Article DE Brain ischemia; inflammation; neuroprotection; stroke ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; INTERCELLULAR-ADHESION MOLECULE-1; CENTRAL-NERVOUS-SYSTEM; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERLEUKIN-1 RECEPTOR ANTAGONIST; NF-KAPPA-B; TRANSIENT FOREBRAIN ISCHEMIA AB Stroke is a frequent cause of long-term disability and death worldwide. Ischemic stroke is more commonly encountered compared to hemorrhagic stroke, and leads to tissue death by ischemia due to occlusion of a cerebral artery. Inflammation is known to result as a result of ischemic injury, long thought to be involved in initiating the recovery and repair process. However, work over the past few decades indicates that aspects of this inflammatory response may in fact be detrimental to stroke outcome. Acutely, inflammation appears to have a detrimental effect, and anti-inflammatory treatments have been been studied as a potential therapeutic target. Chronically, reports suggest that post-ischemic inflammation is also essential for the tissue repairing and remodeling. The majority of the work in this area has centered around innate immune mechanisms, which will be the focus of this review. This review describes the different key players in neuroinflammation and their possible detrimental and protective effects in stroke. A better understanding of the roles of the different immune cells and their temporal profile of damage versus repair will help to clarify more effective modulation of inflammation post stroke. C1 [Yenari, M. A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, Calif 4150 Clement St, San Francisco, CA 94121 USA. EM Yenari@alum.mit.edu FU National Institutes of Health [NS40516]; Veteran's Merit Award; American Heart Association; Uehara Foundation; Veterans Affairs Medical Center, San Francisco, California FX This work was supported by grants from the National Institutes of Health (NS40516, to MY), the Veteran's Merit Award (MY), the American Heart Association (to JYK), and the Uehara Foundation (2013 Research Fellowship, to MK). Grants to MY and JYK were administered by the Northern California Institute for Research and Education, and supported by resources of the Veterans Affairs Medical Center, San Francisco, California. NR 351 TC 30 Z9 33 U1 2 U2 23 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 EI 1875-533X J9 CURR MED CHEM JI Curr. Med. Chem. PD JUN PY 2014 VL 21 IS 18 BP 2076 EP 2097 PG 22 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA AF6UM UT WOS:000334850100006 PM 24372209 ER PT J AU Bobo, WV Reilly-Harrington, NA Ketter, TA Brody, BD Kinrys, G Kemp, DE Shelton, RC McElroy, SL Sylvia, LG Kocsis, JH McInnis, MG Friedman, ES Singh, V Tohen, M Bowden, CL Deckersbach, T Calabrese, JR Thase, ME Nierenberg, AA Rabideau, DJ Schoenfeld, DA Faraone, SV Kamali, M AF Bobo, William V. Reilly-Harrington, Noreen A. Ketter, Terence A. Brody, Benjamin D. Kinrys, Gustavo Kemp, David E. Shelton, Richard C. McElroy, Susan L. Sylvia, Louisa G. Kocsis, James H. McInnis, Melvin G. Friedman, Edward S. Singh, Vivek Tohen, Mauricio Bowden, Charles L. Deckersbach, Thilo Calabrese, Joseph R. Thase, Michael E. Nierenberg, Andrew A. Rabideau, Dustin J. Schoenfeld, David A. Faraone, Stephen V. Kamali, Masoud TI Effect of adjunctive benzodiazepines on clinical outcomes in lithium- or quetiapine-treated outpatients with bipolar I or II disorder: Results from the Bipolar CHOICE trial SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Benzodiazepines; Bipolar disorder; Lithium; Quetiapine; Clinical outcome ID SEVERE MENTAL-ILLNESS; PRESCRIPTION; SCALE; ABUSE AB Background: Little is known about the longer-term effects of adjunctive benzodiazepines on symptom response during treatment in patients with bipolar disorders. Methods: The study sample consisted of 482 patients with bipolar I or II disorder enrolled in a 6-month, randomized, multi-site comparison of lithium- and quetiapine-basecl treatment. Changes in clinical measures (BISS total and subscales, CGI-BP, and CGI-Efficacy Index) were compared between participants who did and did not receive benzodiazepine treatment at baseline or during follow-up. Selected outcomes were also compared between patients who did and did not initiate benzodiazepines during follow-up using stabilized inverse probability weighted analyses. Results: Significant improvement in all outcome measures occurred within each benzodiazepine exposure group. Benzodiazepine users (at baseline or during follow-up) experienced significantly less improvement in BISS total, BISS irritability, and CGI-BP scores than did benzodiazepine non-users. There were no significant differences in these measures between patients who did and did not initiate benzodiazepines during follow-up in the weighted analyses. There was no significant effect of benzodiazepine use on any outcome measure in patients with comorbid anxiety or substance use disorders. Limitations: This is a secondary analysis of data from a randomized effectiveness trial that was not designed to address differential treatment response according to benzodiazepine use Conclusions: Adjunctive benzodiazepines may not significantly affect clinical outcome in lithium- or quetiapine-treated patients with bipolar l or II disorder over 6 months, after controlling for potential confounding factors. (C) 2014 Elsevier B.V. All rights reserved. C1 [Bobo, William V.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA. [Reilly-Harrington, Noreen A.; Kinrys, Gustavo; Sylvia, Louisa G.; Deckersbach, Thilo; Nierenberg, Andrew A.; Rabideau, Dustin J.; Schoenfeld, David A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ketter, Terence A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Brody, Benjamin D.; Kocsis, James H.] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA. [Kemp, David E.; Calabrese, Joseph R.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Shelton, Richard C.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA. [McElroy, Susan L.] Univ Cincinnati, Coll Med, Lindner Ctr HOPE, Cincinnati, OH USA. [McInnis, Melvin G.; Kamali, Masoud] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. [Friedman, Edward S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Singh, Vivek; Bowden, Charles L.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Tohen, Mauricio] Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. [Thase, Michael E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Faraone, Stephen V.] SUNY Syracuse, Upstate Med Univ, Syracuse, NY USA. RP Bobo, WV (reprint author), 200 First St SW,Generose 2A, Rochester, MN 55904 USA. EM bobo.william@mayo.edu OI Faraone, Stephen/0000-0002-9217-3982 FU AHRQ [R01 HS019371-01]; NIMH [MH087747] FX This study was funded by AHRQ Grant R01 HS019371-01. Dr Bobo was supported, in part, by NIMH Grant MH087747. NR 17 TC 5 Z9 5 U1 2 U2 10 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 JUN 1 PY 2014 VL 161 BP 30 EP 35 DI 10.1016/j.jad.2014.02.046 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA AF5GE UT WOS:000334741200006 PM 24751304 ER PT J AU Sheets, ES Duncan, LE Bjornsson, AS Craighead, LW Craighead, WE AF Sheets, Erin S. Duncan, Laramie E. Bjornsson, Andri S. Craighead, Linda W. Craighead, W. Edward TI Personality Pathology Factors Predict Recurrent Major Depressive Disorder in Emerging Adults SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE personality disorders; depression; factor structure; Axis II pathology; emerging adulthood ID EARLY ADOLESCENT BOYS; CONDUCT PROBLEMS; YOUNG-ADULTS; INTERPERSONAL STRESS; NATURAL COURSE; MENTAL-HEALTH; EARLY-ONSET; FOLLOW-UP; SYMPTOMS; COMORBIDITY AB Objective Prior investigations consistently indicate that personality pathology is a risk factor for recurrence of major depressive disorder (MDD). Lack of emipircal support, however, for the Diagnostic and Statistical Manual of Mental Disorders (DSM) Fourth Edition organization of Axis II disorders supports the investigation of empirically derived factors of personality pathology as predictors of recurrence. Method A sample of 130 previously depressed emerging adults (80% female; aged 18 to 21 years) were assessed for personality disorder symptoms at baseline. Participants were then followed for 18 months to identify MDD recurrence during the first 2 years of college. Results Based on a previous factor analysis of DSM personality disorder criteria, eight personality pathology factors were examined as predictors of MDD recurrence. Survival analysis indicated that factors of interpersonal hypersensitivity, antisocial conduct, and social anxiety were associated with increased risk of MDD recurrence. Conclusions These findings suggest that an empirically based approach to personality pathology organization may yield useful predictors of MDD recurrence during emerging adulthood. C1 [Sheets, Erin S.] Colby Coll, Waterville, ME 04901 USA. [Duncan, Laramie E.] Harvard Univ, Sch Publ Hlth, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Bjornsson, Andri S.] Univ Iceland, IS-101 Reykjavik, Iceland. [Craighead, Linda W.; Craighead, W. Edward] Emory Univ, Atlanta, GA 30322 USA. RP Sheets, ES (reprint author), Colby Coll, Dept Psychol, 5550 Mayflower Hill, Waterville, ME 04901 USA. EM essheets@colby.edu FU NIMH NIH HHS [R21-MH-59629] NR 48 TC 5 Z9 5 U1 1 U2 13 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 JUN PY 2014 VL 70 IS 6 BP 536 EP 545 DI 10.1002/jclp.22028 PG 10 WC Psychology, Clinical SC Psychology GA AF6TB UT WOS:000334846400005 PM 23852879 ER PT J AU Stanford, FC Durkin, MW Stallworth, JR Powell, CK Poston, MB Blair, SN AF Stanford, Fatima Cody Durkin, Martin W. Stallworth, James Rast Powell, Caroline Keller Poston, Mary Beth Blair, Steven N. TI Factors that Influence Physicians' and Medical Students' Confidence in Counseling Patients About Physical Activity SO JOURNAL OF PRIMARY PREVENTION LA English DT Article DE Physicians; Exercise; Medical students; Physician's role; United States Department of Health and Human Services; Healthy people programs ID PRIMARY-CARE PHYSICIANS; RANDOMIZED CONTROLLED-TRIAL; EXERCISE; HEALTH; WEIGHT; ADVICE; PRESCRIPTION; BEHAVIORS; DOCTORS; FITNESS AB Less than half of US adults and two-thirds of US high school students do not meet current US guidelines for physical activity. We examined which factors promoted physicians' and medical students' confidence in counseling patients about physical activity. We established an online exercise survey targeting attending physicians, resident and fellow physicians, and medical students to determine their current level of physical activity and confidence in counseling patients about physical activity. We compared their personal level of physical activity with the 2008 Physical Activity Guidelines of the US Department of Health and Human Services (USDHHS). We administered a survey in 2009 and 2010 that used the short form of the International Physical Activity Questionnaire. A total of 1,949 individuals responded to the survey, of whom 1,751 (i.e., 566 attending physicians, 138 fellow physicians, 806 resident physicians, and 215 medical students) were included in this analysis. After adjusting for their BMI, the odds that physicians and medical students who met USDHHS guidelines for vigorous activity would express confidence in their ability to provide exercise counseling were more than twice that of physicians who did not meet these guidelines. Individuals who were overweight were less likely to be confident than those with normal BMI, after adjusting for whether they met the vigorous exercise guidelines. Physicians with obesity were even less likely to express confidence in regards to exercise counseling. We conclude that physicians and medical students who had a normal BMI and met vigorous USDHHS guidelines were more likely to feel confident about counseling their patients about physical activity. Our findings suggest that graduate medical school education should focus on health promotion in their students, as this will likely lead to improved health behaviors in their students' patient populations. C1 [Stanford, Fatima Cody] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Durkin, Martin W.] Palmetto Hlth Richland Res Adm, Columbia, SC USA. [Stallworth, James Rast; Powell, Caroline Keller; Poston, Mary Beth] Univ S Carolina, Sch Med, Palmetto Hlth Richland, Columbia, SC USA. [Blair, Steven N.] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. RP Stanford, FC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Staniford St,4th Floor, Boston, MA 02114 USA. EM fstanford@mgh.harvard.edu OI Stanford, Fatima/0000-0003-4616-533X NR 34 TC 5 Z9 5 U1 2 U2 23 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0278-095X EI 1573-6547 J9 J PRIM PREV JI J. Prim. Prev. PD JUN PY 2014 VL 35 IS 3 BP 193 EP 201 DI 10.1007/s10935-014-0345-4 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AF8AW UT WOS:000334938400006 PM 24682887 ER PT J AU Sharma, J Gray, KP Harshman, LC Evan, C Nakabayashi, M Fichorova, R Rider, J Mucci, L Kantoff, PW Sweeney, CJ AF Sharma, Jaya Gray, Kathryn P. Harshman, Lauren C. Evan, Carolyn Nakabayashi, Mari Fichorova, Raina Rider, Jennifer Mucci, Lorelei Kantoff, Philip W. Sweeney, Christopher J. TI Elevated IL-8, TNF-alpha, and MCP-1 in men with metastatic prostate cancer starting androgen-deprivation therapy (ADT) are associated with shorter time to castration-resistance and overall survival SO PROSTATE LA English DT Article DE prostate cancer; TNF-alpha and MCP-1; inflammation; elevated IL-8 ID NF-KAPPA-B; INTRAEPITHELIAL NEOPLASIA; RANDOMIZED-TRIAL; INTERLEUKIN-6; ACTIVATION; TARGET; GROWTH; CARCINOGENESIS; PARTHENOLIDE; SUPPRESSION AB BACKGROUND Chemokines and cytokines have been implicated in progression to castration-resistant prostate cancer (CRPC). METHODS Retrospective data were accessed from 122 men with serum samples drawn at a median of 0.5 months after starting ADT for metastatic prostate cancer. MCP-1, IL-1-beta, IL-2, IL-8, IL-6, and TNF-alpha levels were measured by multiplex electrochemiluminescence assays. A multivariable Cox model assessed the association of time to CRPC and overall survival by the protein levels and adjusted for clinical variables (age and prostate specific antigen (PSA) levels at start of ADT, race, ECOG status, and extent of metastases). Associations were reported as hazard ratio (HR) with 95% confidence interval (CI). RESULTS Median follow-up and overall survival were 44 and 42.2 months, respectively. ECOG performance status (>= 1 vs. 0) was negatively associated with overall survival [HR = 2.8 (1.1-7.0), P = 0.03], and PSA nadir < 0.2 was predictive of longer time to development of CRPC [HR = 0.3 (0.2-0.5), P < 0.0001]. The HR for time to CRPC by protein above the median was 1.4 (95% CI: 0.9, 2.2, P = 0.13) for IL-8; 1.3 (95% CI: 0.8, 2, P = 0.18) for TNF-alpha; 1.0 (95% CI: 0.7, 1.6, P = 0.95) for MCP-1. The HR for median overall survival for protein levels above the median was: 1.9 (95% CI: 1.0, 3.5, P = 0.04) for IL-8; 2.0 (95% CI: 1.1, 3.5, P = 0.02) for TNF-alpha; 1.7 (95% CI: 1.7, 3.0, P = 0.08) for MCP-1. There was no association with IL-1-beta, IL-2, or IL-6. CONCLUSION Higher levels of inflammation-associated cytokines correlate with poorer prostate cancer outcomes and may guide strategies to improve prostate cancer therapy. Prostate 74:820-828, 2014. (c) 2014 Wiley Periodicals, Inc. C1 [Sharma, Jaya; Harshman, Lauren C.; Evan, Carolyn; Nakabayashi, Mari; Kantoff, Philip W.; Sweeney, Christopher J.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Gray, Kathryn P.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gray, Kathryn P.; Rider, Jennifer; Mucci, Lorelei] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Harshman, Lauren C.; Fichorova, Raina; Kantoff, Philip W.; Sweeney, Christopher J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Fichorova, Raina; Rider, Jennifer] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Sweeney, Christopher J.] Hoosier Oncol Grp, Indianapolis, IN USA. RP Sweeney, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,D1230, Boston, MA 02215 USA. EM christopher_sweeney@dfci.harvard.edu RI Fichorova, Raina/G-9969-2014 NR 39 TC 17 Z9 17 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-4137 EI 1097-0045 J9 PROSTATE JI Prostate PD JUN PY 2014 VL 74 IS 8 BP 820 EP 828 DI 10.1002/pros.22788 PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA AF7KK UT WOS:000334893800003 PM 24668612 ER PT J AU Chang, CNY Huang, AJ Bredella, MA Kattapuram, SV Torriani, M AF Chang, Connie Y. Huang, Ambrose J. Bredella, Miriam A. Kattapuram, Susan V. Torriani, Martin TI Association between distal ulnar morphology and extensor carpi ulnaris tendon pathology SO SKELETAL RADIOLOGY LA English DT Article DE Wrist; Extensor carpi ulnaris; Ulna; Ulnar variance ID TRIANGULAR FIBROCARTILAGE COMPLEX; ULNOCARPAL IMPACTION SYNDROME; VARIANCE; FOREARM; ARTHROGRAPHY AB The purpose of this study was to evaluate the association between distal ulnar morphology and extensor carpi ulnaris (ECU) tendon pathology. We retrospectively reviewed 71 adult wrist MRI studies with ECU tendon pathology (tenosynovitis, tendinopathy, or tear), and/or ECU subluxation. Subjects did not have a history of trauma, surgery, infection, or inflammatory arthritis. MRI studies from 46 subjects without ECU tendon pathology or subluxation were used as controls. The following morphological parameters of the distal ulna were measured independently by two readers: ulnar variance relative to radius, ulnar styloid process length, ECU groove depth and length. Subjects and controls were compared using Student's t test. Inter-observer agreement (ICC) was calculated. There was a significant correlation between negative ulnar variance and ECU tendon pathology (reader 1 [R1], P = 0.01; reader 2 [R2], P < 0.0001; R1 and R2 averaged data, P < 0.0001) and ECU tendon subluxation (P = 0.001; P = 0.0001; P < 0.0001). In subjects with ECU tendon subluxation there was also a trend toward a shorter length (P = 0.3; P < 0.0001; P = 0.001) and a shallower ECU groove (P = 0.01; P = 0.03; P = 0.01; R1 and R2 averaged data with Bonferroni correction, P = 0.08). ECU groove depth (P = 0.6; P = 0.8; P = 0.9) and groove length (P = 0.1; P = 0.4; P = 0.7) showed no significant correlation with ECU tendon pathology, and length of the ulnar styloid process showed no significant correlation with ECU tendon pathology (P = 0.2; P = 0.3; P = 0.2) or subluxation (P = 0.4; P = 0.5; P = 0.5). Inter-observer agreement (ICC) was > 0.64 for all parameters. Distal ulnar morphology may be associated with ECU tendon abnormalities. C1 [Chang, Connie Y.; Huang, Ambrose J.; Bredella, Miriam A.; Kattapuram, Susan V.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Chang, Connie Y.; Huang, Ambrose J.; Bredella, Miriam A.; Kattapuram, Susan V.; Torriani, Martin] Harvard Univ, Sch Med, Boston, MA USA. RP Chang, CNY (reprint author), 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM cychang@mgh.harvard.edu NR 25 TC 4 Z9 4 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 EI 1432-2161 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JUN PY 2014 VL 43 IS 6 BP 793 EP 800 DI 10.1007/s00256-014-1845-2 PG 8 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA AF8AY UT WOS:000334938600007 PM 24595441 ER PT J AU Baik, SH Cha, MY Hyun, YM Cho, H Hamza, B Kim, DK Han, SH Choi, H Kim, KH Moon, M Lee, J Kim, M Irimia, D Mook-Jung, I AF Baik, Sung Hoon Cha, Moon-Yong Hyun, Young-Min Cho, Hansang Hamza, Bashar Kim, Dong Kyu Han, Sun-Ho Choi, Heesun Kim, Kyung Ho Moon, Minho Lee, Jeewoo Kim, Minsoo Irimia, Daniel Mook-Jung, Inhee TI Migration of neutrophils targeting amyloid plaques in Alzheimer's disease mouse model SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; Neutrophils; Amyloid plaques; Immune cells ID INNATE IMMUNE-RESPONSE; TRANSGENIC MICE; BETA; BRAIN; NEURODEGENERATION; MICROGLIA; SYSTEM AB Immune responses in the brain are thought to play a role in disorders of the central nervous system, but an understanding of the process underlying how immune cells get into the brain and their fate there remains unclear. In this study, we used a 2-photon microscopy to reveal that neutrophils infiltrate brain and migrate toward amyloid plaques in a mouse model of Alzheimer's disease. These findings suggest a new molecular process underlying the pathophysiology of Alzheimer's disease. (C) 2014 Elsevier Inc. All rights reserved. C1 [Baik, Sung Hoon; Cha, Moon-Yong; Kim, Dong Kyu; Han, Sun-Ho; Choi, Heesun; Kim, Kyung Ho; Moon, Minho; Kim, Minsoo; Mook-Jung, Inhee] Seoul Natl Univ, Coll Med, Dept Biochem & Biomed Sci, Seoul 110799, South Korea. [Hyun, Young-Min; Kim, Minsoo] Univ Rochester, David H Smith Ctr Vaccine Biol & Immunol, Dept Microbiol & Immunol, Rochester, NY USA. [Lee, Jeewoo] Seoul Natl Univ, Coll Pharm, Dept Pharmacol, Seoul, South Korea. [Cho, Hansang; Hamza, Bashar; Irimia, Daniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, BioMEMS Resource Ctr, Boston, MA USA. RP Mook-Jung, I (reprint author), Seoul Natl Univ, Coll Med, Dept Biochem & Biomed Sci, 103 Daehak Ro, Seoul 110799, South Korea. EM inhee@snu.ac.kr OI Irimia, Daniel/0000-0001-7347-2082 FU National Research Foundation of Korea [2012R1A2A1A01002881, MRC [2011-0030738]]; Korea National Institute of Health ROAD R&D Program Project [A092058]; Korea Institute of Science and Technology Institutional Program [2E24242- 13e135]; Cooperative Research Program for Agriculture Science & Technology Development [PJ009103] FX This work was supported by grants from the National Research Foundation of Korea (2012R1A2A1A01002881, MRC [2011-0030738]); the Korea National Institute of Health ROAD R&D Program Project (A092058), Korea Institute of Science and Technology Institutional Program (2E24242-13-135) for Inhee Mook-Jung, and the Cooperative Research Program for Agriculture Science & Technology Development (PJ009103) for Kyung Ho Kim. NR 18 TC 22 Z9 22 U1 1 U2 17 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 JUN PY 2014 VL 35 IS 6 BP 1286 EP 1292 DI 10.1016/j.neurobiolaging.2014.01.003 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AE4RO UT WOS:000333970800008 PM 24485508 ER PT J AU Coutu, JP Chen, JJ Rosas, HD Salat, DH AF Coutu, Jean-Philippe Chen, J. Jean Rosas, H. Diana Salat, David H. TI Non-Gaussian water diffusion in aging white matter SO NEUROBIOLOGY OF AGING LA English DT Article DE MRI; Diffusional kurtosis imaging; Diffusion tensor imaging; Aging; White matter integrity; Region-of-interest analysis; Tract-based spatial statistics; K-means clustering; Multivariate analysis ID SPATIAL STATISTICS; CLINICAL-APPLICATIONS; ALZHEIMERS-DISEASE; VOXELWISE ANALYSIS; NERVOUS-SYSTEM; BRAIN; KURTOSIS; MRI; INTEGRITY; DECLINE AB Age-associated white matter degeneration has been well documented and is likely an important mechanism contributing to cognitive decline in older adults. Recent work has explored a range of noninvasive neuroimaging procedures to differentially highlight alterations in the tissue microenvironment. Diffusional kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI) that accounts for non-Gaussian water diffusion and can reflect alterations in the distribution and diffusion properties of tissue compartments. We used DKI to produce whole-brain voxel-based maps of mean, axial, and radial diffusional kurtoses, quantitative indices of the tissue microstructure's diffusional heterogeneity, in 111 participants ranging from the age of 33 to 91 years. As suggested from prior DTI studies, greater age was associated with alterations in white-matter tissue microstructure, which was reflected by a reduction in all 3 DKI metrics. Prominent effects were found in prefrontal and association white matter compared with relatively preserved primary motor and visual areas. Although DKI metrics co-varied with DTI metrics on a global level, DKI provided unique regional sensitivity to the effects of age not available with DTI. DKI metrics were additionally useful in combination with DTI metrics for the classification of regions according to their multivariate "diffusion footprint", or pattern of relative age effect sizes. It is possible that the specific multivariate patterns of age-associated changes measured are representative of different types of microstructural pathology. These results suggest that DKI provides important complementary indices of brain microstructure for the study of brain aging and neurologic disease. (C) 2014 Elsevier Inc. All rights reserved. C1 [Coutu, Jean-Philippe; Chen, J. Jean; Rosas, H. Diana; Salat, David H.] Harvard Univ, Massachusetts Gen Hosp, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Sch Med, Charlestown, MA USA. [Coutu, Jean-Philippe] MIT, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Cambridge, MA 02139 USA. [Chen, J. Jean; Salat, David H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rosas, H. Diana] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. RP Coutu, JP (reprint author), MIT, Div Hlth Sci & Technol, Bldg E25-518,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM coutu@nmr.mgh.harvard.edu OI /0000-0003-4895-5642 FU National Institutes of Health [R01NR010827, NS042861, NS058793]; Center for Functional Neuroimaging Technologies [P41RR14075]; Biomedical Technology Program of the National Center for Research Resources (NCRR); National Institutes of Health; NCRR Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program [S10RR021110, S10RR023401, S10RR019307, S10RR019254, S10RR023043]; Advanced Multimodal Neuroimaging Training Program at the MGH/HST Athinoula A. Martinos Center for Biomedical Imaging [2T90DA022759]; Natural Sciences and Engineering Research Council of Canada; Fonds Quebecois de la Recherche sur la Nature et les Technologies FX This study was funded by the National Institutes of Health grants R01NR010827, NS042861, NS058793 and was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant numbers S10RR021110, S10RR023401, S10RR019307, S10RR019254, and S10RR023043. J.P.C. was funded by the Advanced Multimodal Neuroimaging Training Program (2T90DA022759; P.I. Bruce Rosen) at the MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, the Natural Sciences and Engineering Research Council of Canada and the Fonds Quebecois de la Recherche sur la Nature et les Technologies. NR 55 TC 27 Z9 29 U1 1 U2 20 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 JUN PY 2014 VL 35 IS 6 BP 1412 EP 1421 DI 10.1016/j.neurobiolaging.2013.12.001 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA AE4RO UT WOS:000333970800022 PM 24378085 ER PT J AU Gin, JL Stein, JA Heslin, KC Dobalian, A AF Gin, June L. Stein, Judith A. Heslin, Kevin C. Dobalian, Aram TI Responding to risk: Awareness and action after the September 11, 2001 terrorist attacks SO SAFETY SCIENCE LA English DT Article DE Emergency preparedness; Terrorism; Social psychology; Pre-disposing factors; Disaster planning; Cognitive awareness ID INDIVIDUAL-RESPONSE; PREPAREDNESS; PERSPECTIVE; CANADA; HAZARD; STATES; MODEL AB Adoption of preparedness measures among the US public remains low after the expansion of the all-hazards approach to personal preparedness campaigns following the terrorist attacks of September 11, 2001 (9/11). This study sought to understand factors influencing preparedness behavior, particularly how demographics might influence preparedness behavior and whether preparedness actions are related to preparedness attitudes and related behaviors that may prime individuals to take these actions. Using data from the 2008 General Social Survey (n = 1338), we tested a conceptual path model of preparedness that includes demographic variables and three latent variables as mediators of the effects of demographics on preparedness: Cognitive Preparedness; Peer Group Behavior Awareness, and Perceived Effectiveness. The model explains 65% of the variance in preparedness behavior. It suggests that the effects of demographic factors on preparedness actually reflect indirect relationships mediated by predisposing attitudes, behaviors and experiences, specifically, Cognitive Preparedness, Peer Group Behavior Awareness, and Perceived Effectiveness that predispose individuals toward taking preparedness actions. Because these social and cognitive factors reflect behaviors that, unlike fixed demographics, can be shaped by public education programs, efforts to increase public preparedness should focus on improving public awareness, social networks, and more persuasive messaging as keys to increasing preparedness behavior among the US public. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved. C1 [Gin, June L.; Stein, Judith A.; Heslin, Kevin C.; Dobalian, Aram] US Dept Vet Affairs, Vet Emergency Management Evaluat Ctr, North Hills, CA 91343 USA. [Heslin, Kevin C.; Dobalian, Aram] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA. [Dobalian, Aram] UCLA Sch Nursing, Los Angeles, CA USA. RP Gin, JL (reprint author), US Dept Vet Affairs, Vet Emergency Management Evaluat Ctr, 16111 Plummer St,MS-152, North Hills, CA 91343 USA. EM june.gin@va.gov; jastein@ucla.edu; kevin.heslin@va.gov; aram.dobalian@va.gov FU US Department of Veterans Affairs, Veterans Health Administration, Office of Public Health FX This material is based on work supported by the US Department of Veterans Affairs, Veterans Health Administration, Office of Public Health. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the US Department of Veterans Affairs or the US government. The authors thank Michael N. Mitchell for statistical consulting assistance provided on the GSS data set. NR 35 TC 1 Z9 1 U1 4 U2 33 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-7535 EI 1879-1042 J9 SAFETY SCI JI Saf. Sci. PD JUN PY 2014 VL 65 BP 86 EP 92 DI 10.1016/j.ssci.2014.01.001 PG 7 WC Engineering, Industrial; Operations Research & Management Science SC Engineering; Operations Research & Management Science GA AD8JQ UT WOS:000333512700011 ER PT J AU Prashanth, R Roy, SD Mandal, PK Ghosh, S AF Prashanth, R. Roy, Sumantra Dutta Mandal, Pravat K. Ghosh, Shantanu TI Automatic classification and prediction models for early Parkinson's disease diagnosis from SPECT imaging SO EXPERT SYSTEMS WITH APPLICATIONS LA English DT Article DE Computer-aided early diagnosis; Parkinson's disease; Risk prediction; Pattern analysis; Support vector machine; Logistic regression ID ESSENTIAL TREMOR; LOGISTIC-REGRESSION; DOPAMINERGIC SYSTEM; FOLLOW-UP; SWEDDS; IMAGES; SCANS AB Early and accurate diagnosis of Parkinson's disease (PD) is important for early management, proper prognostication and for initiating neuroprotective therapies once they become available. Recent neuroimaging techniques such as dopaminergic imaging using single photon emission computed tomography (SPECT) with I-123-Ioflupane (DaTSCAN) have shown to detect even early stages of the disease. In this paper, we use the striatal binding ratio (SBR) values that are calculated from the I-123-loflupane SPECT scans (as obtained from the Parkinson's progression markers initiative (PPMI) database) for developing automatic classification and prediction/prognostic models for early PD. We used support vector machine (SVM) and logistic regression in the model building process. We observe that the SVM classifier with RBF kernel produced a high accuracy of more than 96% in classifying subjects into early PD and healthy normal; and the logistic model for estimating the risk of PD also produced high degree of fitting with statistical significance indicating its usefulness in PD risk estimation. Hence, we infer that such models have the potential to aid the clinicians in the PD diagnostic process. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Prashanth, R.; Roy, Sumantra Dutta] Indian Inst Technol Delhi, Dept Elect Engn, Delhi, India. [Mandal, Pravat K.] Natl Brain Res Ctr, Neurospect & Neuroimaging Lab, Gurgaon, Haryana, India. [Mandal, Pravat K.] Johns Hopkins Med, Dept Radiol, Baltimore, MD USA. [Ghosh, Shantanu] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Ghosh, Shantanu] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Prashanth, R (reprint author), Indian Inst Technol Delhi, Dept Elect Engn, Delhi, India. EM eez108051@ee.iitd.ac.in RI MANDAL, PRAVAT/C-3705-2009 FU Michael J. Fox Foundation FX PPMI - a public-private partnership - is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including [list of all of the PPMI funding partners found at www.ppmi-info.org/fundingpartners]. NR 36 TC 19 Z9 19 U1 2 U2 42 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0957-4174 EI 1873-6793 J9 EXPERT SYST APPL JI Expert Syst. Appl. PD JUN 1 PY 2014 VL 41 IS 7 BP 3333 EP 3342 DI 10.1016/j.eswa.2013.11.031 PG 10 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic; Operations Research & Management Science SC Computer Science; Engineering; Operations Research & Management Science GA AA3UM UT WOS:000331019800018 ER PT J AU Yoo, B Ghosh, SK Kumar, M Moore, A Yigit, MV Medarova, Z AF Yoo, Byunghee Ghosh, Subrata K. Kumar, Mohanraja Moore, Anna Yigit, Mehmet V. Medarova, Zdravka TI Design of Nanodrugs for miRNA Targeting in Tumor Cells SO JOURNAL OF BIOMEDICAL NANOTECHNOLOGY LA English DT Article DE Gene Silencing; Microrna; Locked Nucleic Acids; Integrin Specific Peptide; Iron Oxide Nanoparticles; Delivery Vehicle ID MAGNETIC NANOPARTICLES; SIRNA DELIVERY; MICRORNAS; BIOGENESIS; CANCER AB The delivery of oligonucleotide antagonists to cytosolic RNA targets such as microRNA represents an avenue for the post-transcriptional control of cellular phenotype. In tumor cells, oncogenic miRNAs, termed oncomirs, are tightly linked to processes that ultimately determine cancer initiation, progression, and response to therapy. Therefore, the capacity to redirect tumor cell fate towards therapeutically beneficial phenotypes holds promise in a future clinical scenario. Previously, we have designed "nanodrugs" for the specific inhibition of oncogenic microRNAs in tumor cells. The basic design of these nanodrugs includes dextran coated iron oxide nanoparticles, conjugated to a tumor-targeting peptide, and a locked nucleic acid (LNA)-modified antisense oligonucleotide that stably binds and inhibits the complementary mature miRNA. Here, we focus on elucidating an optimal nanodrug design for effective miRNA inhibition in tumor cells. Specifically, we investigate the choice of chemical linker for the conjugation of the oligonucleotide to the nanoparticles and evaluate the contribution of tumor-cell targeting to nanodrug uptake and functionality. We find that short labile linkers (SPDP; N-Succinimidyl 3-(2-pyridyldithio)-propionate) are superior to non-labile short linkers (GMBS; N-(gamma-Maleimidobutyryloxy)succinimide ester) or non-labile long linkers (PEG24; Succinimidyl-([N-maleimidopropionamido]-24ethyleneglycol)ester) in terms of their capacity to gain access to the cytosolic cellular compartment and to engage their cognate miRNA. Furthermore, using the nanodrug design that incorporates SPDP as a linker, we establish that the addition of tumor-cell targeting through functionalization of the nanodrug with the alpha v beta 3-specific cyclic RGDfK-PEG peptide does not confer an advantage in vitro at long incubation times required for inhibition. C1 Massachusetts Gen Hosp, Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Yigit, MV (reprint author), SUNY Albany, Dept Chem, RNA Inst, 1400 Washington Ave, Albany, NY 12222 USA. EM myigit@albany.edu; zmedarova@partners.org FU NIH [NCIR00CA129070, NCI-1R01CA163461-01A1]; Breast Cancer Alliance FX This work was supported by grants NCIR00CA129070 and NCI-1R01CA163461-01A1 to ZM by the NIH and the Young Investigator Award to ZM by the Breast Cancer Alliance. NR 27 TC 10 Z9 11 U1 1 U2 108 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 1550-7033 EI 1550-7041 J9 J BIOMED NANOTECHNOL JI J. Biomed. Nanotechnol. PD JUN PY 2014 VL 10 IS 6 BP 1114 EP 1122 DI 10.1166/jbn.2014.1795 PG 9 WC Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Science & Technology - Other Topics; Materials Science GA 276DX UT WOS:000328729400020 PM 24749405 ER PT J AU Imamura, Y Lochhead, P Yamauchi, M Kuchiba, A Qian, ZR Liao, XY Nishihara, R Jung, SY Wu, KN Nosho, K Wang, YE Peng, SY Bass, AJ Haigis, KM Meyerhardt, JA Chan, AT Fuchs, CS Ogino, S AF Imamura, Yu Lochhead, Paul Yamauchi, Mai Kuchiba, Aya Qian, Zhi Rong Liao, Xiaoyun Nishihara, Reiko Jung, Seungyoun Wu, Kana Nosho, Katsuhiko Wang, Yaoyu E. Peng, Shouyong Bass, Adam J. Haigis, Kevin M. Meyerhardt, Jeffrey A. Chan, Andrew T. Fuchs, Charles S. Ogino, Shuji TI Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review SO MOLECULAR CANCER LA English DT Review DE Clinical outcome; Colon cancer; Genetic change; RAF; RAS ID ISLAND METHYLATOR PHENOTYPE; RAS GENE-MUTATIONS; CETUXIMAB PLUS IRINOTECAN; ADVANCED RECTAL-CANCER; K-RAS; COLON-CANCER; MICROSATELLITE INSTABILITY; 1ST-LINE TREATMENT; BRAF MUTATIONS; WILD-TYPE AB Background: KRAS mutations in codons 12 and 13 are established predictive biomarkers for anti-EGFR therapy in colorectal cancer. Previous studies suggest that KRAS codon 61 and 146 mutations may also predict resistance to anti-EGFR therapy in colorectal cancer. However, clinicopathological, molecular, and prognostic features of colorectal carcinoma with KRAS codon 61 or 146 mutation remain unclear. Methods: We utilized a molecular pathological epidemiology database of 1267 colon and rectal cancers in the Nurse's Health Study and the Health Professionals Follow-up Study. We examined KRAS mutations in codons 12, 13, 61 and 146 (assessed by pyrosequencing), in relation to clinicopathological features, and tumor molecular markers, including BRAF and PIK3CA mutations, CpG island methylator phenotype (CIMP), LINE-1 methylation, and microsatellite instability (MSI). Survival analyses were performed in 1067 BRAF-wild-type cancers to avoid confounding by BRAF mutation. Cox proportional hazards models were used to compute mortality hazard ratio, adjusting for potential confounders, including disease stage, PIK3CA mutation, CIMP, LINE-1 hypomethylation, and MSI. Results: KRAS codon 61 mutations were detected in 19 cases (1.5%), and codon 146 mutations in 40 cases (3.2%). Overall KRAS mutation prevalence in colorectal cancers was 40% (=505/1267). Of interest, compared to KRAS-wild-type, overall, KRAS-mutated cancers more frequently exhibited cecal location (24% vs. 12% in KRAS-wild-type; P < 0.0001), CIMP-low (49% vs. 32% in KRAS-wild-type; P < 0.0001), and PIK3CA mutations (24% vs. 11% in KRAS-wild-type; P < 0.0001). These trends were evident irrespective of mutated codon, though statistical power was limited for codon 61 mutants. Neither KRAS codon 61 nor codon 146 mutation was significantly associated with clinical outcome or prognosis in univariate or multivariate analysis [colorectal cancer-specific mortality hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.29-2.26 for codon 61 mutation; colorectal cancer-specific mortality HR = 0.86, 95% CI = 0.42-1.78 for codon 146 mutation]. Conclusions: Tumors with KRAS mutations in codons 61 and 146 account for an appreciable proportion (approximately 5%) of colorectal cancers, and their clinicopathological and molecular features appear generally similar to KRAS codon 12 or 13 mutated cancers. To further assess clinical utility of KRAS codon 61 and 146 testing, large-scale trials are warranted. C1 [Imamura, Yu; Lochhead, Paul; Yamauchi, Mai; Kuchiba, Aya; Qian, Zhi Rong; Liao, Xiaoyun; Nishihara, Reiko; Peng, Shouyong; Bass, Adam J.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Imamura, Yu; Lochhead, Paul; Yamauchi, Mai; Kuchiba, Aya; Qian, Zhi Rong; Liao, Xiaoyun; Nishihara, Reiko; Peng, Shouyong; Bass, Adam J.; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Lochhead, Paul] Univ Aberdeen, Inst Med Sci, Gastrointestinal Res Grp, Aberdeen, Scotland. [Kuchiba, Aya; Nishihara, Reiko; Wu, Kana] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Jung, Seungyoun; Chan, Andrew T.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Nosho, Katsuhiko] Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. [Wang, Yaoyu E.] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Bass, Adam J.] Broad Inst & Harvard, Canc Program, Cambridge, MA USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA USA. [Haigis, Kevin M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Ogino, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Room M422, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu FU U.S. National Institute of Health (NIH) [P01 CA87969, P01 CA55075, UM1 CA167552, P50 CA127003, R01 CA137178, R01 CA151993]; Bennett Family Fund; Entertainment Industry Foundation through National Colorectal Cancer Research Alliance; Harvard University Frank Knox Memorial Fellowship FX We deeply thank hospitals and pathology departments throughout the U.S. for generously providing us with tissue specimens. In addition, we would like to thank the participants and staff of the Nurses' Health Study and the Health Professionals Follow-Up Study, for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. This work was supported by U.S. National Institute of Health (NIH) grants [P01 CA87969 to S. E. Hankinson; P01 CA55075 to W. C. Willett; UM1 CA167552 to W. C. Willett; P50 CA127003 to CSF; R01 CA137178 to ATC; and R01 CA151993 to SO]; and by grants from the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance. ATC is a Damon Runyon Clinical Investigator. PL is a Scottish Government Clinical Academic Fellow and was supported by a Harvard University Frank Knox Memorial Fellowship. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 94 TC 39 Z9 40 U1 3 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD MAY 31 PY 2014 VL 13 AR 135 DI 10.1186/1476-4598-13-135 PG 15 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA AK2OC UT WOS:000338257900004 PM 24885062 ER PT J AU Vergallo, R Jia, HB Soeda, T Tian, JW Jang, IK AF Vergallo, Rocco Jia, Haibo Soeda, Tsunenari Tian, Jinwei Jang, Ik-Kyung TI Interpretation of optical coherence tomography images SO LANCET LA English DT Letter ID PLAQUE C1 [Vergallo, Rocco; Jia, Haibo; Soeda, Tsunenari; Tian, Jinwei; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [Jia, Haibo; Tian, Jinwei] Harbin Med Univ, Key Lab Myocardial Ischemia, Affiliated Hosp 2, Dept Cardiol,Chinese Minist Educ, Harbin, Peoples R China. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. EM ijang@partners.org NR 3 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAY 31 PY 2014 VL 383 IS 9932 BP 1887 EP 1887 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AI4PR UT WOS:000336847800025 PM 24881991 ER PT J AU Colicino, E Power, MC Cox, DG Weisskopf, MG Hou, LF Alexeeff, SE Sanchez-Guerra, M Vokonas, P Spiro, A Schwartz, J Baccarelli, AA AF Colicino, Elena Power, Melinda C. Cox, David G. Weisskopf, Marc G. Hou, Lifang Alexeeff, Stacy E. Sanchez-Guerra, Marco Vokonas, Pantel Spiro, Avron, III Schwartz, Joel Baccarelli, Andrea A. TI Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment SO ENVIRONMENTAL HEALTH LA English DT Article DE mtDNA haplogroups; Air pollution; Black carbon; Cognitive decline; Mini-mental state examination ID AIR-POLLUTION; ULTRAFINE PARTICLES; DNA HAPLOGROUPS; HUMAN MTDNA; EXPOSURE; DISEASE; TREE; MEN AB Background: Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution. Methods: We investigated 582 older men (72 +/- 7 years) in the VA Normative Aging Study cohort with = 4 visits per participant (1.8 in average) between 1995-2007. Low (<= 25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant's address. Results: Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups. Conclusions: The association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects. C1 [Colicino, Elena; Power, Melinda C.; Weisskopf, Marc G.; Alexeeff, Stacy E.; Sanchez-Guerra, Marco; Schwartz, Joel; Baccarelli, Andrea A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Power, Melinda C.; Weisskopf, Marc G.; Schwartz, Joel; Baccarelli, Andrea A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cox, David G.] Ctr Rech Canc Lyon, INSERM, U1052, F-69008 Lyon, France. [Cox, David G.] Pole Rech Translat Lyon, Ctr Lyon Berard, F-69008 Lyon, France. [Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Vokonas, Pantel; Spiro, Avron, III] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Vokonas, Pantel; Spiro, Avron, III] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Colicino, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM ecolicin@hsph.harvard.edu RI Cox, David/A-2023-2009; Colicino, Elena/Q-4973-2016; OI Cox, David/0000-0002-2152-9259; Colicino, Elena/0000-0002-1875-8448; Baccarelli, Andrea/0000-0002-3436-0640 FU National Institute of Environmental Health Sciences (NIEHS) [R01ES021733]; NIEHS [ES015172, ES014663, ES020010, T32 ES007069]; Environmental Protection Agency (EPA) [RD832416]; Cooperative Studies Program/ERIC, US Department of Veterans Affairs; VA Merit Review; CSR&D Research Career Scientist award; US Department of Agriculture, Agricultural Research Service [53-K06-510]; National Institute of Aging (NIA) [F31 AG038233] FX EC is supported by a grant from the National Institute of Environmental Health Sciences (NIEHS) (R01ES021733). Other support comes from NIEHS grants ES015172, ES014663 and ES020010, and Environmental Protection Agency (EPA) grant RD832416. The US Department of Veterans Affairs (VA) Normative Aging Study (NAS) is supported by the Cooperative Studies Program/ERIC, US Department of Veterans Affairs, and is a research component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). Cognitive data collection at the VA NAS was supported by a VA Merit Review and a CSR&D Research Career Scientist award to AS. The views expressed in this paper are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. Additional support was provided by the US Department of Agriculture, Agricultural Research Service (contract 53-K06-510). MCP was supported by grants from the NIEHS (T32 ES007069) and National Institute of Aging (NIA) (F31 AG038233). NR 28 TC 5 Z9 6 U1 3 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD MAY 30 PY 2014 VL 13 AR 42 DI 10.1186/1476-069X-13-42 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA AJ0CU UT WOS:000337317700001 PM 24884505 ER PT J AU Ichinose, F AF Ichinose, Fumito TI H2S in sepsis and shock - A story of mice and men SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 3rd International Conference on H2S Biology and Medicine CY JUN 04-06, 2014 CL Kyoto, JAPAN SP Antibe Therapeut Inc, Sulfagenix, Inc, Fondazione Int Menarini, Asahi Kasei Pharma Corp, Kobayashi Pharmaceut Co, Ltd, Noevir Holdings Co, Ltd C1 [Ichinose, Fumito] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 1089-8603 EI 1089-8611 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAY 30 PY 2014 VL 39 SU 1 BP S4 EP S4 DI 10.1016/j.niox.2014.03.014 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH7UL UT WOS:000336340700012 ER PT J AU Kakinohana, M Kida, K Ichinose, F AF Kakinohana, Manabu Kida, Kotaro Ichinose, Fumito TI Inhaled hydrogen sulfide can prevent delayed neuronal death after spinal cord ischemia in mice SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Meeting Abstract CT 3rd International Conference on H2S Biology and Medicine CY JUN 04-06, 2014 CL Kyoto, JAPAN SP Antibe Therapeut Inc, Sulfagenix, Inc, Fondazione Int Menarini, Asahi Kasei Pharma Corp, Kobayashi Pharmaceut Co, Ltd, Noevir Holdings Co, Ltd C1 [Kakinohana, Manabu] Univ Ryukyus, Dept Anesthesiol, Nishihara, Okinawa 90301, Japan. [Kida, Kotaro; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 EI 1089-8611 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAY 30 PY 2014 VL 39 SU 1 BP S28 EP S28 DI 10.1016/j.niox.2014.03.089 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH7UL UT WOS:000336340700086 ER PT J AU Finkelstein, DM Schoenfeld, DA AF Finkelstein, Dianne M. Schoenfeld, David A. TI A joint test for progression and survival with interval-censored data from a cancer clinical trial SO STATISTICS IN MEDICINE LA English DT Article DE Conditional Expected Score Test (CEST); progression-free survival (PFS); PRO logistic model; interval-censored failure time data ID PROPORTIONAL HAZARDS MODEL; FAILURE TIME DATA; EM ALGORITHM; RANDOMIZED-TRIAL; BREAST-CANCER; TAMOXIFEN; LETROZOLE; THERAPY; EVENT AB Clinical trials often assess efficacy by comparing treatments on the basis of two or more event-time outcomes. In the case of cancer clinical trials, progression-free survival (PFS), which is the minimum of the time from randomization to progression or to death, summarizes the comparison of treatments on the hazards for disease progression and mortality. However, the analysis of PFS does not utilize all the information we have on patients in the trial. First, if both progression and death times are recorded, then information on death time is ignored in the PFS analysis. Second, disease progression is monitored at regular clinic visits, and progression time is recorded as the first visit at which evidence of progression is detected. However, many patients miss or have irregular visits (resulting in interval-censored data) and sometimes die of the cancer before progression was recorded. In this case, the previous progression-free time could provide additional information on the treatment efficacy. The aim of this paper is to propose a method for comparing treatments that could more fully utilize the data on progression and death. We develop a test for treatment effect based on of the joint distribution of progression and survival. The issue of interval censoring is handled using the very simple and intuitive approach of the Conditional Expected Score Test (CEST). We focus on the application of these methods in cancer research. Copyright (c) 2014 John Wiley & Sons, Ltd. C1 [Finkelstein, Dianne M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Finkelstein, Dianne M.] Harvard Univ, Biostat Unit, Boston, MA 02114 USA. RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA. EM dfinkelstein@mgh.harvard.edu FU Avon Foundation; NIH [CA167570, UL1RR025758, CA160233] FX We wish to thank Dr. Paul Goss for allowing us to use the MA 17 data. This work was partially funded by grants from the Avon Foundation and from the NIH: CA167570, UL1RR025758, and CA160233. NR 18 TC 2 Z9 2 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD MAY 30 PY 2014 VL 33 IS 12 BP 1981 EP 1989 DI 10.1002/sim.6096 PG 9 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA AG8PO UT WOS:000335680900001 PM 24500790 ER PT J AU Brown, JR Byrd, JC Coutre, SE Benson, DM Flinn, IW Wagner-Johnston, ND Spurgeon, SE Kahl, BS Bello, C Webb, HK Johnson, DM Peterman, S Li, D Jahn, TM Lannutti, BJ Ulrich, RG Yu, AS Miller, LL Furman, RR AF Brown, Jennifer R. Byrd, John C. Coutre, Steven E. Benson, Don M. Flinn, Ian W. Wagner-Johnston, Nina D. Spurgeon, Stephen E. Kahl, Brad S. Bello, Celeste Webb, Heather K. Johnson, Dave M. Peterman, Sissy Li, Daniel Jahn, Thomas M. Lannutti, Brian J. Ulrich, Roger G. Yu, Albert S. Miller, Langdon L. Furman, Richard R. TI Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110 delta, for relapsed/refractory chronic lymphocytic leukemia SO BLOOD LA English DT Article ID B-CELL MALIGNANCIES; CLINICAL ACTIVITY; FLUDARABINE; RITUXIMAB; LYMPHOMA; LENALIDOMIDE; ACTIVATION; CAL-101; PATHWAY; PI3K AB In a phase 1 trial, idelalisib (GS-1101, CAL-101), a selective inhibitor of the lipid kinase PI3K delta, was evaluated in 54 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) with adverse characteristics including bulky lymphadenopathy (80%), extensive prior therapy (median 5 [range 2-14] prior regimens), treatment-refractory disease (70%), unmutated IGHV (91%), and del17p and/or TP53 mutations (24%). Patients were treated at 6 dose levels of oral idelalisib (range 50-350 mg once or twice daily) and remained on continuous therapy while deriving clinical benefit. Idelalisib-mediated inhibition of PI3K delta led to abrogation of Akt phosphorylation in patient CLL cells and significantly reduced serum levels of CLL-related chemokines. The most commonly observed grade >= 3 adverse events were pneumonia (20%), neutropenic fever (11%), and diarrhea (6%). Idelalisib treatment resulted in nodal responses in 81% of patients. The overall response rate was 72%, with 39% of patients meeting the criteria for partial response per IWCLL 2008 and 33% meeting the recently updated criteria of PR with treatment-induced lymphocytosis.(1,2) The median progression-free survival for all patients was 15.8 months. This study demonstrates the clinical utility of inhibiting the PI3Kd pathway with idelalisib. Our findings support the further development of idelalisib in patients with CLL. These trials were registered at clinicaltrials.gov as #NCT00710528 and #NCT01090414. C1 [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Byrd, John C.; Benson, Don M.] Ohio State Univ, Columbus, OH 43210 USA. [Coutre, Steven E.] Stanford Univ, Stanford, CA 94305 USA. [Flinn, Ian W.] Sarah Cannon Res Inst, Nashville, TN USA. [Wagner-Johnston, Nina D.] Washington Univ, St Louis, MO USA. [Spurgeon, Stephen E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kahl, Brad S.] Univ Wisconsin, Madison, WI USA. [Bello, Celeste] H Lee Moffitt Canc Ctr & Res Inst, Seattle, WA USA. [Webb, Heather K.; Johnson, Dave M.; Peterman, Sissy; Li, Daniel; Jahn, Thomas M.; Lannutti, Brian J.; Ulrich, Roger G.; Yu, Albert S.; Miller, Langdon L.] Gilead Sci Inc, Seattle, WA USA. [Furman, Richard R.] Weill Cornell Med Coll, New York, NY USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Jennifer_brown@dfci.harvard.edu FU Gilead Sciences, Inc (Foster City, CA); Gilead Sciences, Inc (Seattle, WA); Calistoga Pharmaceuticals, Inc (Seattle, WA) FX This study was sponsored and funded by Gilead Sciences, Inc (Foster City, CA and Seattle, WA), and by Calistoga Pharmaceuticals, Inc (Seattle, WA) (now a wholly owned subsidiary of Gilead Sciences, Inc). NR 35 TC 223 Z9 225 U1 3 U2 22 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 29 PY 2014 VL 123 IS 22 BP 3390 EP 3397 DI 10.1182/blood-2013-11-535047 PG 8 WC Hematology SC Hematology GA AQ2LD UT WOS:000342616600013 PM 24615777 ER PT J AU Kahl, BS Spurgeon, SE Furman, RR Flinn, IW Coutre, SE Brown, JR Benson, DM Byrd, JC Peterman, S Cho, Y Yu, A Godfrey, WR Wagner-Johnston, ND AF Kahl, Brad S. Spurgeon, Stephen E. Furman, Richard R. Flinn, Ian W. Coutre, Steven E. Brown, Jennifer R. Benson, Don M. Byrd, John C. Peterman, Sissy Cho, Yoonjin Yu, Albert Godfrey, Wayne R. Wagner-Johnston, Nina D. TI A phase 1 study of the PI3K delta inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL) SO BLOOD LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE P110-DELTA; MTOR CONSTITUTIVE ACTIVATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; B-CELL; MARGINAL ZONE; CYCLIN D1; PI3K; CYCLOPHOSPHAMIDE; COMBINATION AB Idelalisib, an oral inhibitor of phosphatidylinositol-3-kinase delta (PI3K delta), was evaluated in a 48-week phase 1 study (50-350 mg daily or twice daily) enrolling 40 patients with relapsed or refractory mantle cell lymphoma (MCL). Primary outcome was safety and dose-limiting toxicity (DLT). Secondary outcomes were pharmacokinetic parameters, pharmacodynamic effects, overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR). Patients without DLT and no evidence of disease progression after 48 weeks enrolled in the extension study. Patients had median age of 69 years (range, 52-83) and receivedmedian of 4 prior therapies (1-14); 17 of 40 patients (43%) were refractory to their most recent treatment. Median duration of idelalisib treatment was 3.5 months (range, 0.7-30.7), with 6 (15%) continuing extension treatment. Commongrade >= 3 adverse events (AEs) included (total%/grade >= 3%) diarrhea (40/18), nausea (33/5), pyrexia (28/0), fatigue (25/3), rash (23/3), decreased appetite (20/15), upper respiratory infection (20/0), pneumonia (13/10), and alanine transaminase or aspartate transaminase elevations (60/20). ORR was 16 of 40 patients (40%), with CR in 2 of 40 patients (5%). Median DOR was 2.7 months, median PFS was 3.7 months, and 1-year PFS was 22%. These data provide proof of concept that targeting PI3K delta is a viable strategy and worthy of additional study in MCL. This trial was registered at www.clinicaltrials.gov as #NCT00710528. C1 [Kahl, Brad S.] Univ Wisconsin, Dept Med, Carbone Canc Ctr, Madison, WI USA. [Spurgeon, Stephen E.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Furman, Richard R.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Flinn, Ian W.] Sarah Cannon Res Inst, Nashville, TN USA. [Coutre, Steven E.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Benson, Don M.; Byrd, John C.] Ohio State Univ, Dept Med, Columbus, OH 43210 USA. [Peterman, Sissy; Cho, Yoonjin; Yu, Albert; Godfrey, Wayne R.] Gilead Sci Inc, Seattle, WA USA. [Wagner-Johnston, Nina D.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Kahl, BS (reprint author), 4059 Wisconsin Inst Med Res, 1111 Highland Ave, Madison, WI 53705 USA. EM bsk@medicine.wisc.edu FU Gilead Sciences, Inc. (Foster City, CA); Gilead Sciences, Inc. (Seattle, WA); Calistoga Pharmaceuticals, Inc. of Seattle, WA FX This clinical study was sponsored and funded by Gilead Sciences, Inc. (Foster City, CA, and Seattle, WA) and Calistoga Pharmaceuticals, Inc. of Seattle, WA (acquired by Gilead Sciences, Inc.). NR 38 TC 93 Z9 96 U1 3 U2 12 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 29 PY 2014 VL 123 IS 22 BP 3398 EP 3405 DI 10.1182/blood-2013-11-537555 PG 8 WC Hematology SC Hematology GA AQ2LD UT WOS:000342616600014 PM 24615778 ER PT J AU Flinn, IW Kahl, BS Leonard, JP Furman, RR Brown, JR Byrd, JC Wagner-Johnston, ND Coutre, SE Benson, DM Peterman, S Cho, Y Webb, HK Johnson, DM Yu, AS Ulrich, RG Godfrey, WR Miller, LL Spurgeon, SE AF Flinn, Ian W. Kahl, Brad S. Leonard, John P. Furman, Richard R. Brown, Jennifer R. Byrd, John C. Wagner-Johnston, Nina D. Coutre, Steve E. Benson, Don M. Peterman, Sissy Cho, Yoonjin Webb, Heather K. Johnson, David M. Yu, Albert S. Ulrich, Roger G. Godfrey, Wayne R. Miller, Langdon L. Spurgeon, Stephen E. TI Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-delta, as therapy for previously treated indolent non-Hodgkin lymphoma SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL MALIGNANCIES; REFRACTORY INDOLENT; RITUXIMAB; PI3K; BENDAMUSTINE; MULTICENTER; CAL-101 AB Idelalisib (GS-1101, CAL-101), an oral inhibitor of phosphatidylinositol 3-kinase-delta, was evaluated in a phase I study in 64 patients with relapsed indolent non-Hodgkin lymphoma (iNHL). Patients had a median (range) age of 64 (32-91) years, 34 (53%) had bulky disease (>= 1 lymph nodes >= 5 cm), and 37 (58%) had refractory disease. Patients had received a median (range) of 4 (1-10) prior therapies. Eight dose regimens of idelalisib were evaluated; idelalisib was taken once or twice daily continuously at doses ranging from 50 to 350 mg. After 48 weeks, patients still benefitting (n = 19; 30%) enrolled into an extension study. Adverse events (AEs) occurring in 20% or more patients (total%/grade >= 3%) included diarrhea (36/8), fatigue (36/3), nausea (25/3), rash (25/3), pyrexia (20/3), and chills (20/0). Laboratory abnormalities included neutropenia (44/23), anemia (31/5), thrombocytopenia (25/11), and serum transaminase elevations (48/25). Twelve (19%) patients discontinued therapy due to AEs. Idelalisib induced disease regression in 46/54 (85%) of evaluable patients achieving an overall response rate of 30/64 (47%), with 1 patient having a complete response (1.6%). Median duration of response was 18.4 months, median progression-free survival was 7.6 months. Idelalisib is well tolerated and active in heavily pretreated, relapsed/refractory patients with iNHL. These trials were registered at clinicaltrials.gov as NCT00710528 and NCT01090414. C1 [Flinn, Ian W.] Sarah Cannon Res Inst, Nashville, TN 37203 USA. [Kahl, Brad S.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Leonard, John P.; Furman, Richard R.] Weill Cornell Med Coll, New York, NY USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Byrd, John C.; Benson, Don M.] Ohio State Univ, Columbus, OH 43210 USA. [Wagner-Johnston, Nina D.] Washington Univ, Sch Med, St Louis, MO USA. [Coutre, Steve E.] Stanford Univ, Ctr Canc, Stanford, CA 94305 USA. [Peterman, Sissy; Cho, Yoonjin; Webb, Heather K.; Johnson, David M.; Yu, Albert S.; Ulrich, Roger G.; Godfrey, Wayne R.; Miller, Langdon L.] Gilead Sci Inc, Seattle, WA USA. [Spurgeon, Stephen E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Flinn, IW (reprint author), Sarah Cannon Res Inst, 250 25th Ave North, Nashville, TN 37203 USA. EM iflinn@tnonc.com FU Gilead Sciences, Inc (Foster City, CA); Gilead Sciences, Inc (Seattle, WA); Calistoga Pharmaceuticals, Inc (Seattle, WA) FX This clinical study was sponsored and funded by Gilead Sciences, Inc (Foster City, CA and Seattle, WA) and by Calistoga Pharmaceuticals, Inc (Seattle, WA) (acquired by Gilead Sciences, Inc.). NR 34 TC 82 Z9 82 U1 3 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 29 PY 2014 VL 123 IS 22 BP 3406 EP 3413 DI 10.1182/blood-2013-11-538546 PG 8 WC Hematology SC Hematology GA AQ2LD UT WOS:000342616600015 PM 24615776 ER PT J AU Aplenc, R Zhang, MJ Sung, LL Zhu, XC Ho, VT Cooke, K Dvorak, C Hale, G Isola, LM Lazarus, HM McCarthy, PL Olsson, R Pulsipher, M Pasquini, MC Bunin, N AF Aplenc, Richard Zhang, Mei-Jie Sung, Lillian Zhu, Xiaochun Ho, Vincent T. Cooke, Kenneth Dvorak, Christopher Hale, Gregory Isola, Luis M. Lazarus, Hillard M. McCarthy, Philip L. Olsson, Richard Pulsipher, Michael Pasquini, Marcelo C. Bunin, Nancy CA Ctr Int Blood Marrow Transplant TI Effect of body mass in children with hematologic malignancies undergoing allogeneic bone marrow transplantation SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; OBESITY; LEUKEMIA; OVERWEIGHT; ADOLESCENTS; OUTCOMES; MORTALITY; DISEASES; IMPACT AB The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median ageandrace were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P < .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P < .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P < .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM. C1 [Aplenc, Richard; Bunin, Nancy] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Zhang, Mei-Jie; Zhu, Xiaochun; Pasquini, Marcelo C.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Sung, Lillian] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Ho, Vincent T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cooke, Kenneth; Lazarus, Hillard M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Dvorak, Christopher] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hale, Gregory] Univ S Florida, All Childrens Hosp, St Petersburg, FL 33701 USA. [Isola, Luis M.] Mt Sinai Hosp, New York, NY 10029 USA. [McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Olsson, Richard] Karolinska Inst, Stockholm, Sweden. [Pulsipher, Michael] Univ Utah, Sch Med, Salt Lake City, UT USA. RP Pasquini, MC (reprint author), 9200 West Wisconsin Ave,CCC5500, Milwaukee, WI 53226 USA. EM mpasquini@mcw.edu OI Olsson, Richard/0000-0001-5970-2128 FU Public Health Service from the National Institutes of Health National Cancer Institute [U24-CA076518]; National Heart, Lung and Blood Institute; National Institute of Allergy and Infectious Diseases; National Heart, Lung and Blood Institute [5U10HL069294]; National Cancer Institute; Health Resources and Services Administration [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin, Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; NMDP; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St. Baldrick's Foundation; StemCyte; A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Institutes of Health National Cancer Institute, the National Heart, Lung and Blood Institute, and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 5U10HL069294 from National Heart, Lung and Blood Institute and National Cancer Institute; a contract HHSH250201200016C with Health Resources and Services Administration; 2 grants (N00014-12-1-0142 and N00014-13-1-0039) from the Office of Naval Research; and grants from Actinium Pharmaceuticals, Allos Therapeutics, Inc., Amgen, Inc., nnonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, Blue Cross and Blue Shield Association, Celgene Corporation, Fred Hutchinson Cancer Research Center, Fresenius-Biotech North America, Inc., Gamida Cell Teva Joint Venture Ltd., Genentech, Inc., Gentium SpA, Genzyme Corporation, GlaxoSmithKline, Health Research, Inc. Roswell Park Cancer Institute, HistoGenetics, Inc., Incyte Corporation, Jeff Gordon Children's Foundation, Kiadis Pharma, The Leukemia & Lymphoma Society, Medac GmbH, The Medical College of Wisconsin, Merck & Co, Inc., Millennium: The Takeda Oncology Co., Milliman USA, Inc., Miltenyi Biotec, Inc., NMDP, Onyx Pharmaceuticals, Optum Healthcare Solutions, Inc., Osiris Therapeutics, Inc., Otsuka America Pharmaceutical, Inc., Perkin Elmer, Inc., Remedy Informatics, Sanofi US, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, Inc., St. Baldrick's Foundation, StemCyte, A Global Cord Blood Therapeutics Co., Stemsoft Software, Inc., Swedish Orphan Biovitrum, Tarix Pharmaceuticals, TerumoBCT, Teva Neuroscience, Inc., THERAKOS, Inc., University of Minnesota, University of Utah, and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the U.S. Government. NR 32 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 29 PY 2014 VL 123 IS 22 BP 3504 EP 3511 DI 10.1182/blood-2013-03-490334 PG 8 WC Hematology SC Hematology GA AQ2LD UT WOS:000342616600026 PM 24711663 ER PT J AU Rampal, R Al-Shahrour, F Abdel-Wahab, O Patel, JP Brunel, JP Mermel, CH Bass, AJ Pretz, J Ahn, J Hricik, T Kilpivaara, O Wadleigh, M Busque, L Gilliland, DG Golub, TR Ebert, BL Levine, RL AF Rampal, Raajit Al-Shahrour, Fatima Abdel-Wahab, Omar Patel, Jay P. Brunel, Jean-Philippe Mermel, Craig H. Bass, Adam J. Pretz, Jennifer Ahn, Jihae Hricik, Todd Kilpivaara, Outi Wadleigh, Martha Busque, Lambert Gilliland, D. Gary Golub, Todd R. Ebert, Benjamin L. Levine, Ross L. TI Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; GENE-EXPRESSION; MYELOID MALIGNANCIES; ESSENTIAL THROMBOCYTHEMIA; LEUKEMIC TRANSFORMATION; V617F MUTATION; TET2; MYELOFIBROSIS AB Genomic studies have identified somatic alterations in the majority of myeloproliferative neoplasms (MPN) patients, including JAK2 mutations in the majority of MPN patients and CALR mutations in JAK2-negative MPN patients. However, the role of JAK-STAT pathway activation in different MPNs, and in patients without JAK2 mutations, has not been definitively delineated. We used expression profiling, single nucleotide polymorphism arrays, and mutational profiling to investigate a well-characterized cohort of MPN patients. MPN patients with homozygous JAK2V617F mutations were characterized by a distinctive transcriptional profile. Notably, a transcriptional signature consistent with activated JAK2 signaling is seen in allMPN patients regardless of clinical phenotype ormutational status. In addition, the activated JAK2 signature was present in patients with somaticCALRmutations. Conversely, weidentified a gene expression signature ofCALRmutations; this signaturewas significantly enriched in JAK2-mutant MPN patients consistent with a shared mechanism of transformation by JAK2 and CALR mutations. We also identified a transcriptional signature of TET2 mutations in MPN patent samples. Our data indicate that MPN patients, regardless of diagnosis or JAK2 mutational status, are characterized by a distinct gene expression signature with upregulation of JAK-STAT target genes, demonstrating the central importance of the JAK-STAT pathway in MPN pathogenesis. C1 [Rampal, Raajit; Abdel-Wahab, Omar; Patel, Jay P.; Ahn, Jihae; Hricik, Todd; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Rampal, Raajit; Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY 10065 USA. [Rampal, Raajit; Abdel-Wahab, Omar; Levine, Ross L.] Weill Cornell Med Coll, New York, NY USA. [Al-Shahrour, Fatima] Spanish Natl Canc Res Ctr, Translat Bioinformat Unit, Clin Res Programme, Madrid, Spain. [Brunel, Jean-Philippe; Mermel, Craig H.; Bass, Adam J.; Pretz, Jennifer; Golub, Todd R.; Ebert, Benjamin L.] Broad Inst Harvard Univ, Cambridge, MA USA. [Brunel, Jean-Philippe; Mermel, Craig H.; Bass, Adam J.; Pretz, Jennifer; Golub, Todd R.; Ebert, Benjamin L.] MIT, Cambridge, MA 02139 USA. [Mermel, Craig H.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Mermel, Craig H.] Dept Pathol, Boston, MA USA. [Bass, Adam J.; Pretz, Jennifer; Wadleigh, Martha] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kilpivaara, Outi] Univ Helsinki, Dept Med Genet, Genome Scale Biol Res Program, Helsinki, Finland. [Busque, Lambert] Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ, Canada. [Busque, Lambert] Maisonneuve Rosemont Hosp, Dept Hematol, Montreal, PQ, Canada. [Busque, Lambert] Univ Montreal, Montreal, PQ, Canada. [Gilliland, D. Gary] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Golub, Todd R.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Ebert, Benjamin L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol,Dept Med, Boston, MA 02115 USA. RP Ebert, BL (reprint author), Brigham & Womens Hosp, 1 Blackfan Circle, Boston, MA 02115 USA. EM bebert@partners.org; leviner@mskcc.org OI Abdel-Wahab, Omar/0000-0002-3907-6171 FU Myeloproliferative Neoplasm Foundation; Starr Cancer Consortium; National Institutes of Health, National Cancer Institute [1R01CA151949-01] FX This work was supported by grants from the Myeloproliferative Neoplasm Foundation (R. L. L., B. L. E.), the Starr Cancer Consortium (D. G. G., T. R. G., B. L. E., R. L. L.), and the National Institutes of Health, National Cancer Institute (grant 1R01CA151949-01) (R. L. L.). R. L. L. and B. L. E. are Leukemia and Lymphoma Society Scholars, and O.A.-W. and R. R. are American Society of Hematology Scholars. NR 66 TC 84 Z9 91 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 29 PY 2014 VL 123 IS 22 BP E123 EP E133 DI 10.1182/blood-2014-02-554634 PG 11 WC Hematology SC Hematology GA AQ2LD UT WOS:000342616600001 PM 24740812 ER PT J AU Yasmeen, A Ringe, R Derking, R Cupo, A Julien, JP Burton, DR Ward, AB Wilson, IA Sanders, RW Moore, JP Klasse, PJ AF Yasmeen, Anila Ringe, Rajesh Derking, Ronald Cupo, Albert Julien, Jean-Philippe Burton, Dennis R. Ward, Andrew B. Wilson, Ian A. Sanders, Rogier W. Moore, John P. Klasse, Per Johan TI Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits SO RETROVIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN TRIMERS; HUMAN MONOCLONAL-ANTIBODIES; INTERMOLECULAR DISULFIDE BOND; VACCINE DEVELOPMENT; POTENT NEUTRALIZATION; IMMUNOGEN DESIGN; VARIABLE LOOPS; GP41 SUBUNITS; CD4 BINDING AB Background: The trimeric envelope glycoproteins (Env) on the surface of HIV-1 virions are the targets for neutralizing antibodies (NAbs). No candidate HIV-1 immunogen has yet induced potent, broadly active NAbs (bNAbs). Part of the explanation may be that previously tested Env proteins inadequately mimic the functional, native Env complex. Trimerization and the proteolytic processing of Env precursors into gp120 and gp41 profoundly alter antigenicity, but soluble cleaved trimers are too unstable to serve as immunogens. By introducing stabilizing mutations (SOSIP), we constructed soluble, cleaved Env trimers derived from the HIV-1 subtype A isolate BG505 that resemble native Env spikes on virions both structurally and antigenically. Results: We used surface plasmon resonance (SPR) to quantify antibody binding to different forms of BG505 Env: the proteolytically cleaved SOSIP. 664 trimers, cleaved gp120-gp41(ECTO) protomers, and gp120 monomers. Non-NAbs to the CD4-binding site bound only marginally to the trimers but equally well to gp120-gp41(ECTO) protomers and gp120 monomers, whereas the bNAb VRC01, directed to the CD4bs, bound to all three forms. In contrast, bNAbs to V1V2 glycan-dependent epitopes bound preferentially (PG9 and PG16) or exclusively (PGT145) to trimers. We also explored the antigenic consequences of three different features of SOSIP.664 gp140 trimers: the engineered inter-subunit disulfide bond, the trimer-stabilizing I559P change in gp41(ECTO), and proteolytic cleavage at the gp120-gp41ECTO junction. Each of these three features incrementally promoted native-like trimer antigenicity. We compared Fab and IgG versions of bNAbs and validated a bivalent model of IgG binding. The NAbs showed widely divergent binding kinetics and degrees of binding to native-like BG505 SOSIP.664. High off-rate constants and low stoichiometric estimates of NAb binding were associated with large amounts of residual infectivity after NAb neutralization of the corresponding BG505.T332N pseudovirus. Conclusions: The antigenicity and structural integrity of cleaved BG505 SOSIP. 664 trimers render these proteins good mimics of functional Env spikes on virions. In contrast, uncleaved gp140s antigenically resemble individual gp120-gp41(ECTO) protomers and gp120 monomers, but not native trimers. Although NAb binding to functional trimers may thus be both necessary and sufficient for neutralization, the kinetics and stoichiometry of the interaction influence the neutralizing efficacy of individual NAbs. C1 [Yasmeen, Anila; Ringe, Rajesh; Cupo, Albert; Sanders, Rogier W.; Moore, John P.; Klasse, Per Johan] Cornell Univ, Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. [Derking, Ronald; Sanders, Rogier W.] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands. [Julien, Jean-Philippe; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA. [Julien, Jean-Philippe; Ward, Andrew B.; Wilson, Ian A.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Burton, Dennis R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02115 USA. [Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Klasse, PJ (reprint author), Cornell Univ, Weill Cornell Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. EM pek2003@med.cornell.edu RI Ward, Andrew/F-9203-2014 OI Ward, Andrew/0000-0001-7153-3769 FU NIH [P01 AI82362, R37 AI36082]; IAVI Neutralizing Antibody Consortium; Aids fonds Netherlands [2011032]; Canadian Institutes of Health Research (CIHR) Fellowship; Netherlands Organization for Scientific Research (NWO) [91711314]; European Research Council [ERC-StG-2011-280829-SHEV] FX This work was supported by NIH grants P01 AI82362, R37 AI36082, by the IAVI Neutralizing Antibody Consortium, and by the Aids fonds Netherlands, grant 2011032. JPJ is a recipient of a Canadian Institutes of Health Research (CIHR) Fellowship. RWS is a recipient of a Vidi grant from the Netherlands Organization for Scientific Research (NWO; 91711314) and a Starting Investigator Grant from the European Research Council (ERC-StG-2011-280829-SHEV). We are grateful to John Mascola and James Robinson for reagents and to Kevin de Los Reyes, Michael Golabek, and Jacob Korzun for excellent technical assistance. NR 93 TC 53 Z9 53 U1 2 U2 26 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD MAY 29 PY 2014 VL 11 AR 41 DI 10.1186/1742-4690-11-41 PG 17 WC Virology SC Virology GA AK2KB UT WOS:000338247000001 PM 24884783 ER PT J AU Meng, C Kuster, B Culhane, AC Gholami, AM AF Meng, Chen Kuster, Bernhard Culhane, Aedin C. Gholami, Amin Moghaddas TI A multivariate approach to the integration of multi-omics datasets SO BMC BIOINFORMATICS LA English DT Article DE Multivariate analysis; Multiple co-inertia; Data integration; Omic data; Visualization ID GENE-EXPRESSION DATA; CO-INERTIA ANALYSIS; PRINCIPAL COMPONENT ANALYSIS; CANCER-CELL LINE; RNA-SEQ; OVARIAN-CARCINOMA; CROSS-PLATFORM; MESSENGER-RNA; PANEL; MICROARRAY AB Background: To leverage the potential of multi-omics studies, exploratory data analysis methods that provide systematic integration and comparison of multiple layers of omics information are required. We describe multiple co-inertia analysis (MCIA), an exploratory data analysis method that identifies co-relationships between multiple high dimensional datasets. Based on a covariance optimization criterion, MCIA simultaneously projects several datasets into the same dimensional space, transforming diverse sets of features onto the same scale, to extract the most variant from each dataset and facilitate biological interpretation and pathway analysis. Results: We demonstrate integration of multiple layers of information using MCIA, applied to two typical "omics" research scenarios. The integration of transcriptome and proteome profiles of cells in the NCI-60 cancer cell line panel revealed distinct, complementary features, which together increased the coverage and power of pathway analysis. Our analysis highlighted the importance of the leukemia extravasation signaling pathway in leukemia that was not highly ranked in the analysis of any individual dataset. Secondly, we compared transcriptome profiles of high grade serous ovarian tumors that were obtained, on two different microarray platforms and next generation RNA-sequencing, to identify the most informative platform and extract robust biomarkers of molecular subtypes. We discovered that the variance of RNA-sequencing data processed using RPKM had greater variance than that with MapSplice and RSEM. We provided novel markers highly associated to tumor molecular subtype combined from four data platforms. MCIA is implemented and available in the R/Bioconductor "omicade4" package. Conclusion: We believe MCIA is an attractive method for data integration and visualization of several datasets of multi-omics features observed on the same set of individuals. The method is not dependent on feature annotation, and thus it can extract important features even when there are not present across all datasets. MCIA provides simple graphical representations for the identification of relationships between large datasets. C1 [Meng, Chen; Kuster, Bernhard; Gholami, Amin Moghaddas] Tech Univ Munich, Chair Prote & Bioanalyt, Freising Weihenstephan, Germany. [Kuster, Bernhard] Ctr Integrated Prot Sci Munich, Freising Weihenstephan, Germany. [Culhane, Aedin C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Culhane, Aedin C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Culhane, AC (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM aedin@jimmy.harvard.edu; amin@tum.de RI Kuster, Bernhard/Q-6031-2016 OI Kuster, Bernhard/0000-0002-9094-1677 FU Dana-Farber Cancer Institute Women's Cancers Program, Claudia Adams Barr foundation; National Cancer Institute at the National Institutes of Health [1RC4CA156551-01, 1U19CA148065] FX The authors gratefully acknowledge Hannes Hahne and Mathias Wilhelm of TUM and Curtis Huttenhower of Harvard School of Public Health for critical reading of the manuscript. Funding for this work was provided by Dana-Farber Cancer Institute Women's Cancers Program, the Claudia Adams Barr foundation and the National Cancer Institute at the National Institutes of Health [grant numbers 1RC4CA156551-01, 1U19CA148065]. NR 60 TC 27 Z9 28 U1 2 U2 25 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAY 29 PY 2014 VL 15 AR 162 DI 10.1186/1471-2105-15-162 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA AJ0CR UT WOS:000337317300001 PM 24884486 ER PT J AU Quackenbush, J AF Quackenbush, John TI PERSPECTIVE Learning to share SO NATURE LA English DT Editorial Material C1 Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. RP Quackenbush, J (reprint author), Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. EM johnq@jimmy.harvard.edu FU NHLBI NIH HHS [R01 HL111759] NR 0 TC 0 Z9 0 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD MAY 29 PY 2014 VL 509 IS 7502 BP S68 EP S68 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH9JC UT WOS:000336457100010 PM 24870827 ER PT J AU Kradin, RL Fidias, P Digumarthy, S Mark, EJ AF Kradin, Richard L. Fidias, Panos Digumarthy, Subba Mark, Eugene J. TI Case 17-2014: A 64-Year-Old Man with Chest Pain and a Pleural Effusion SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LUNG-CANCER; MALIGNANT MESOTHELIOMA; ASBESTOS EXPOSURE; PHASE-III; EPIDEMIOLOGY; CISPLATIN; SURVEILLANCE; POPULATION; PROGRAM C1 [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kradin, Richard L.; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fidias, Panos] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Digumarthy, Subba] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kradin, Richard L.; Fidias, Panos] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kradin, Richard L.; Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Digumarthy, Subba] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU Genentech FX Drs. Kradin and Mark report receiving payments for providing expert testimony in litigation regarding asbestos on behalf of patients. Dr. Fidias reports receiving fees from Genentech for serving on an advisory board. No other potential conflict of interest relevant to this article was reported. NR 24 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 29 PY 2014 VL 370 IS 22 BP 2132 EP 2140 DI 10.1056/NEJMcpc1400835 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AH9BM UT WOS:000336434000012 PM 24869724 ER PT J AU Narasimha, AM Kaulich, M Shapiro, GS Choi, YJ Sicinski, P Dowdy, SF AF Narasimha, Anil M. Kaulich, Manuel Shapiro, Gary S. Choi, Yoon J. Sicinski, Piotr Dowdy, Steven F. TI Cyclin D activates the Rb tumor suppressor by mono-phosphorylation SO ELIFE LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; CELL-CYCLE; DNA-DAMAGE; MYOGENIC DIFFERENTIATION; ECTOPIC EXPRESSION; SKELETAL-MUSCLE; CDK COMPLEXES; PROTEIN; KINASE; INHIBITION AB The widely accepted model of G(1) cell cycle progression proposes that cyclin D: Cdk4/6 inactivates the Rb tumor suppressor during early G(1) phase by progressive multi-phosphorylation, termed hypo-phosphorylation, to release E2F transcription factors. However, this model remains unproven biochemically and the biologically active form(s) of Rb remains unknown. Here we find that Rb is exclusively mono-phosphorylated in early G(1) phase by cyclin D:Cdk4/6. Mono-phosphorylated Rb is composed of 14 independent isoforms that are all targeted by the E1a oncoprotein, but show preferential E2F binding patterns. At the late G(1) Restriction Point, cyclin E: Cdk2 inactivates Rb by quantum hyper-phosphorylation. Cells undergoing a DNA damage response activate cyclin D: Cdk4/6 to generate mono-phosphorylated Rb that regulates global transcription, whereas cells undergoing differentiation utilize un-phosphorylated Rb. These observations fundamentally change our understanding of G(1) cell cycle progression and show that mono-phosphorylated Rb, generated by cyclin D:Cdk4/6, is the only Rb isoform in early G(1) phase. C1 [Narasimha, Anil M.; Kaulich, Manuel; Shapiro, Gary S.; Dowdy, Steven F.] UCSD Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Choi, Yoon J.; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. [Choi, Yoon J.; Sicinski, Piotr] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. RP Dowdy, SF (reprint author), UCSD Sch Med, Dept Cellular & Mol Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM sdowdy@ucsd.edu NR 53 TC 35 Z9 35 U1 2 U2 4 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD MAY 29 PY 2014 VL 3 AR e02872 DI 10.7554/eLife.02872 PG 45 WC Biology SC Life Sciences & Biomedicine - Other Topics GA AI2DA UT WOS:000336666200003 ER PT J AU Baffy, G Loscalzo, J AF Baffy, Gyoergy Loscalzo, Joseph TI Complexity and network dynamics in physiological adaptation: An integrated view SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Homeostasis; Allostasis; Complex adaptive systems; Chaotic exploration; Phase space; Attractor networks ID UNCOUPLING PROTEINS; ATTRACTOR LANDSCAPE; INSULIN-RESISTANCE; METABOLIC SYNDROME; SELF-ORGANIZATION; ALLOSTATIC LOAD; FEEDBACK LOOPS; GENE-THERAPY; OBESITY; DISEASE AB Living organisms constantly interact with their surroundings and sustain internal stability against perturbations. This dynamic process follows three fundamental strategies (restore, explore, and abandon) articulated in historical concepts of physiological adaptation such as homeostasis, allostasis, and the general adaptation syndrome. These strategies correspond to elementary forms of behavior (ordered, chaotic, and static) in complex adaptive systems and invite a network-based analysis of the operational characteristics, allowing us to propose an integrated framework of physiological adaptation from a complex network perspective. Applicability of this concept is illustrated by analyzing molecular and cellular mechanisms of adaptation in response to the pervasive challenge of obesity, a chronic condition resulting from sustained nutrient excess that prompts chaotic exploration for system stability associated with tradeoffs and a risk of adverse outcomes such as diabetes, cardiovascular disease, and cancer. Deconstruction of this complexity holds the promise of gaining novel insights into physiological adaptation in health and disease. Published by Elsevier Inc. C1 [Baffy, Gyoergy] VA Boston Healthcare Syst, Dept Med, Boston, MA 02130 USA. [Baffy, Gyoergy; Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. RP Baffy, G (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,Room 6A-46, Boston, MA 02130 USA. EM gbaffy@partners.org FU NHLBI NIH HHS [R37 HL061795, U01 HL108630] NR 104 TC 6 Z9 6 U1 6 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD MAY 28 PY 2014 VL 131 BP 49 EP 56 DI 10.1016/j.physbeh.2014.04.018 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA AJ7HA UT WOS:000337866600007 PM 24751342 ER PT J AU Ferlemi, AV Avgoustatos, D Kokkosis, AG Protonotarios, V Constantinou, C Margarity, M AF Ferlemi, Anastasia-Varvara Avgoustatos, Dionisis Kokkosis, Alexandros G. Protonotarios, Vasilis Constantinou, Caterina Margarity, Marigoula TI Lead-induced effects on learning/memory and fear/anxiety are correlated with disturbances in specific cholinesterase isoform activity and redox imbalance in adult brain SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Lead; Learning/memory; Anxiety-like behavior; Acetylcholinesterase; Redox balance; Correlation analysis ID LIPID-PEROXIDATION PRODUCTS; ELEVATED PLUS-MAZE; OXIDATIVE STRESS; RAT-BRAIN; MEMORY CONSOLIDATION; IN-VIVO; ANTIOXIDANT ENZYMES; GENE-EXPRESSION; MOUSE-BRAIN; ACETYLCHOLINESTERASE AB The aim of the present study was to investigate whether the underlying mechanism of lead (Pb)-induced effects on learning/memory and fear/anxiety behavior involves changes either on AChE G4 (most abundant in brain) or on G1 isoform activity, and/or to a putative local disruption of oxidant/antioxidant balance. Adult male mice were randomly divided into two groups (18 animals/group): a vehicle group [500 ppm (mg/L) CH3COONa/day for 4 weeks in their drinking water] and a Pb-treated group [500 ppm Pb(CH3COO)(2)/day for 4 weeks in their drinking water]. At the end of the treatment period, mice were subjected to the behavioral tasks. Learning/memory was tested by step-through passive avoidance test, whereas fear/anxiety was studied using the elevated plus-maze and thigmotaxis tests. Pb levels in mice brain were determined using atomic absorption spectrometry. AChE activity was determined colorimetrically, and GSH and MDA levels fluorometrically in whole brain minus cerebellum, cerebral cortex, midbrain, hippocampus, striatum and cerebellum. The possible correlations between learning/memory or fear/anxiety behavior with the AChE activity and/or the lipid peroxidation levels and GSH content were also examined. Pb consumption caused significant deficits on mice learning/memory ability and increased anxiety. The consumption of the Pb solution inhibited the activity of the two AChE isoforms in all brain regions tested. Moreover, Pb exposure increased lipid peroxidation and decreased GSH levels in all brain regions examined. Spearman correlation analysis revealed that the coefficients between the particular behaviors, AChE activity and redox balance were brain region- and AChE isoform-specific. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ferlemi, Anastasia-Varvara; Avgoustatos, Dionisis; Kokkosis, Alexandros G.; Margarity, Marigoula] Univ Patras, Dept Biol, Lab Human & Anim Physiol, Patras 26500, Greece. [Protonotarios, Vasilis] Lavrion Technol & Cultural Pk, Lavrion 19500, Greece. [Constantinou, Caterina] Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Surg Lab,Dept Surg, Boston, MA 02114 USA. [Constantinou, Caterina] Harvard Univ, Sch Med, Shrines Burns Inst, Boston, MA 02114 USA. RP Constantinou, C (reprint author), Univ Patras, Pharmacol Lab, Dept Med, Patras 26500, Greece. EM cconst12@yahoo.com; margar@upatras.gr OI Constantinou, Caterina/0000-0003-3589-0739 NR 67 TC 12 Z9 12 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD MAY 28 PY 2014 VL 131 BP 115 EP 122 DI 10.1016/j.physbeh.2014.04.033 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA AJ7HA UT WOS:000337866600018 PM 24768645 ER PT J AU Ahmed, OJ Vijayan, S AF Ahmed, Omar J. Vijayan, Sujith TI The Roles of Sleep-Wake States and Brain Rhythms in Epileptic Seizure Onset SO JOURNAL OF NEUROSCIENCE LA English DT Editorial Material ID TETANUS TOXIN MODEL; THETA-OSCILLATIONS C1 [Ahmed, Omar J.; Vijayan, Sujith] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Ahmed, Omar J.; Vijayan, Sujith] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vijayan, Sujith] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Ahmed, OJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Thier 423, Boston, MA 02114 USA. EM omar.j.ahmed@gmail.com FU NINDS NIH HHS [F32 NS083208] NR 12 TC 2 Z9 2 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 28 PY 2014 VL 34 IS 22 BP 7395 EP 7397 DI 10.1523/JNEUROSCI.1168-14.2014 PG 3 WC Neurosciences SC Neurosciences & Neurology GA AI8CE UT WOS:000337131800001 PM 24872545 ER PT J AU Zhang, QX Ren, H Baker, GL AF Zhang, Quanxuan Ren, Hong Baker, Gregory L. TI A practical and scalable process to selectively monofunctionalize water-soluble alpha,omega-diols SO TETRAHEDRON LETTERS LA English DT Article DE Monofunctionalization; Water-soluble alpha,omega-diols; THP ether protection and deprotection; Scalable ID SYMMETRICAL DIOLS; ALCOHOLS; MONOPROTECTION; ACID AB A practical protocol for rapid and scalable synthesis of monofunctionalized alpha,omega-diols using a simple and inexpensive THP ether protection/deprotection strategy was described. Use of inexpensive DHP source and ease to remove excess water-soluble alpha,omega-diols and THP ether after deprotection render the process scale-friendly without need of column chromatographic separation. The application of present method was also illustrated in the preparation of heterobifunctional diols and well-defined extended oligo (ethylene glycol). (C) 2014 Elsevier Ltd. All rights reserved. C1 [Zhang, Quanxuan; Baker, Gregory L.] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. [Ren, Hong] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Ren, Hong] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Sch Med,Dept Radiol, Charlestown, MA 02129 USA. RP Zhang, QX (reprint author), Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. EM zhangqua@msu.edu RI Ren, Hong/J-5191-2015 OI Ren, Hong/0000-0003-0375-0360 NR 23 TC 3 Z9 3 U1 2 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAY 28 PY 2014 VL 55 IS 22 BP 3384 EP 3386 DI 10.1016/j.tetlet.2014.04.066 PG 3 WC Chemistry, Organic SC Chemistry GA AI8XG UT WOS:000337209700026 ER PT J AU Rogers, T Milkman, KL Volpp, KG AF Rogers, Todd Milkman, Katherine L. Volpp, Kevin G. TI Commitment Devices Using Initiatives to Change Behavior SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID SMOKING-CESSATION C1 [Rogers, Todd] Harvard Univ, Kennedy Sch, Boston, MA 02115 USA. [Milkman, Katherine L.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Philadelphia VA Med Ctr, Perelman Sch Med, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. RP Volpp, KG (reprint author), Univ Penn, Philadelphia VA Med Ctr, Perelman Sch Med, Ctr Hlth Incent & Behav Econ, 423 Guardian Dr,1120 Blockley Hall, Philadelphia, PA 19104 USA. EM volpp70@exchange.upenn.edu NR 7 TC 11 Z9 11 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 28 PY 2014 VL 311 IS 20 BP 2065 EP 2066 DI 10.1001/jama.2014.3485 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA AH8MQ UT WOS:000336392400018 PM 24777472 ER PT J AU Cotton, PB Durkalski, V Romagnuolo, J Pauls, Q Fogel, E Tarnasky, P Aliperti, G Freeman, M Kozarek, R Jamidar, P Wilcox, M Serrano, J Brawman-Mintzer, O Elta, G Mauldin, P Thornhill, A Hawes, R Wood-Williams, A Orrell, K Drossman, D Robuck, P AF Cotton, Peter B. Durkalski, Valerie Romagnuolo, Joseph Pauls, Qi Fogel, Evan Tarnasky, Paul Aliperti, Giuseppe Freeman, Martin Kozarek, Richard Jamidar, Priya Wilcox, Mel Serrano, Jose Brawman-Mintzer, Olga Elta, Grace Mauldin, Patrick Thornhill, Andre Hawes, Robert Wood-Williams, April Orrell, Kyle Drossman, Douglas Robuck, Patricia TI Effect of Endoscopic Sphincterotomy for Suspected Sphincter of Oddi Dysfunction on Pain-Related Disability Following Cholecystectomy The EPISOD Randomized Clinical Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; FUNCTIONAL GASTROINTESTINAL DISORDERS; FINDINGS TYPE-I; HEALTH-STATUS; RISK-FACTORS; DSM-IV; ERCP; GALLBLADDER; SYMPTOMS; DISEASE AB IMPORTANCE Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde cholangiopancreatography (ERCP) with manometry and sphincterotomy. OBJECTIVE To determine whether endoscopic sphincterotomy reduces pain and whether sphincter manometric pressure is predictive of pain relief. DESIGN, SETTING, AND PATIENTS Multicenter, sham-controlled, randomized trial involving 214 patients with pain after cholecystectomy without significant abnormalities on imaging or laboratory studies, and no prior sphincter treatment or pancreatitis randomly assigned (August 6, 2008-March 23, 2012) to undergo sphincterotomy or sham therapy at 7 referral medical centers. One-year follow-up was blinded. The final follow-up visit was March 21, 2013. INTERVENTIONS After ERCP, patients were randomized 2: 1 to sphincterotomy (n = 141) or sham (n = 73) irrespective of manometry findings. Those randomized to sphincterotomy with elevated pancreatic sphincter pressures were randomized again (1: 1) to biliary or to both biliary and pancreatic sphincterotomies. Seventy-two were entered into an observational study with conventional ERCP managemeny. MAIN OUTCOMES AND MEASURES Success of treatment was defined as less than 6 days of disability due to pain in the prior 90 days both at months 9 and 12 after randomization, with no narcotic use and no further sphincter intervention. RESULTS Twenty-seven patients (37%; 95% CI, 25.9%-48.1%) in the sham treatment group vs 32 (23%; 95% CI, 15.8%-29.6%) in the sphincterotomy group experienced successful treatment (adjusted risk difference, -15.6%; 95% CI, -28.0% to -3.3%; P =.01). Of the patients with pancreatic sphincter hypertension, 14 (30%; 95% CI, 16.7%-42.9%) who underwent dual sphincterotomy and 10 (20%; 95% CI, 8.7%-30.5%) who underwent biliary sphincterotomy alone experienced successful treatment. Thirty-seven treated patients (26%; 95% CI, 19%-34%) and 25 patients (34%; 95% CI, 23%-45%) in the sham group underwent repeat ERCP interventions (P =.22). Manometry results were not associated with the outcome. No clinical subgroups appeared to benefit from sphincterotomy more than others. Pancreatitis occurred in 15 patients (11%) after primary sphincterotomies and in 11 patients (15%) in the sham group. Of the nonrandomized patients in the observational study group, 5 (24%; 95% CI, 6%-42%) who underwent biliary sphincterotomy, 12 (31%; 95% CI, 16%-45%) who underwent dual sphincterotomy, and 2 (17%; 95% CI, 0%-38%) who did not undergo sphincterotomy had successful treatment. CONCLUSIONS AND RELEVANCE In patients with abdominal pain after cholecystectomy undergoing ERCP with manometry, sphincterotomy vs sham did not reduce disability due to pain. These findings do not support ERCP and sphincterotomy for these patients. C1 [Cotton, Peter B.; Durkalski, Valerie; Romagnuolo, Joseph; Pauls, Qi; Mauldin, Patrick; Thornhill, Andre; Hawes, Robert; Wood-Williams, April; Orrell, Kyle] Med Univ S Carolina, Charleston, SC 29425 USA. [Fogel, Evan] Indiana Univ, Indianapolis, IN 46204 USA. [Tarnasky, Paul] Dallas Med Ctr, Dallas, TX USA. [Aliperti, Giuseppe] Midwest Therapeut Endoscopy Consultants, St Louis, MO USA. [Freeman, Martin] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Kozarek, Richard] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Jamidar, Priya] Yale Univ, New Haven, CT USA. [Wilcox, Mel] Univ Alabama Birmingham, Birmingham, AL USA. [Serrano, Jose; Robuck, Patricia] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. [Brawman-Mintzer, Olga] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Elta, Grace] Univ Michigan, Ann Arbor, MI 48109 USA. [Hawes, Robert] Florida Hosp, Orlando, FL USA. [Drossman, Douglas] Univ N Carolina, Chapel Hill, NC USA. [Drossman, Douglas] Drossman Gastroenterol PLLC, Chapel Hill, NC USA. RP Cotton, PB (reprint author), Med Univ S Carolina, Ctr Digest Dis, ART 7094,MSC 290,25 Courtenay Dr, Charleston, SC 29425 USA. EM cottonp@musc.edu FU National Institutes of Diabetes and Digestive and Kidney Diseases [U01 DK074739] FX This study was funded by grant U01 DK074739 from the National Institutes of Diabetes and Digestive and Kidney Diseases. NR 40 TC 38 Z9 39 U1 12 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 28 PY 2014 VL 311 IS 20 BP 2101 EP 2109 DI 10.1001/jama.2014.5220 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA AH8MQ UT WOS:000336392400026 PM 24867013 ER PT J AU Arany, PR Cho, A Hunt, TD Sidhu, G Shin, K Hahm, E Huang, GX Weaver, J Chen, ACH Padwa, BL Hamblin, MR Barcellos-Hoff, MH Kulkarni, AB Mooney, DJ AF Arany, Praveen R. Cho, Andrew Hunt, Tristan D. Sidhu, Gursimran Shin, Kyungsup Hahm, Eason Huang, George X. Weaver, James Chen, Aaron Chih-Hao Padwa, Bonnie L. Hamblin, Michael R. Barcellos-Hoff, Mary Helen Kulkarni, Ashok B. Mooney, David J. TI Photoactivation of Endogenous Latent Transforming Growth Factor-beta 1 Directs Dental Stem Cell Differentiation for Regeneration SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID GROWTH-FACTOR-BETA; LEVEL LASER IRRADIATION; IN-VITRO; PULP COMPLEX; BONE-MARROW; ACTIVATION; TGF-BETA-1; AMELOBLASTS; PROTEINS; MATRIX AB Rapid advancements in the field of stem cell biology have led to many current efforts to exploit stem cells as therapeutic agents in regenerative medicine. However, current ex vivo cell manipulations common to most regenerative approaches create a variety of technical and regulatory hurdles to their clinical translation, and even simpler approaches that use exogenous factors to differentiate tissue-resident stem cells carry significant off-target side effects. We show that non-ionizing, low-power laser (LPL) treatment can instead be used as a minimally invasive tool to activate an endogenous latent growth factor complex, transforming growth factor-beta 1 (TGF-beta 1), that subsequently differentiates host stem cells to promote tissue regeneration. LPL treatment induced reactive oxygen species (ROS) in a dose-dependent manner, which, in turn, activated latent TGF-beta 1 (LTGF-beta 1) via a specific methionine residue (at position 253 on LAP). Laser-activated TGF-beta 1 was capable of differentiating human dental stem cells in vitro. Further, an in vivo pulp capping model in rat teeth demonstrated significant increase in dentin regeneration after LPL treatment. These in vivo effects were abrogated in TGF-LPL-induced receptor II (TGF-beta RII) conditional knockout (DSPP(Cre)TGF-beta RIIfl/fl) mice or when wild-type mice were given a TGF-beta RI inhibitor. These findings indicate a pivotal role for TGF-beta in mediating LPL-induced dental tissue regeneration. More broadly, this work outlines a mechanistic basis for harnessing resident stem cells with a light-activated endogenous cue for clinical regenerative applications. C1 [Arany, Praveen R.; Hunt, Tristan D.; Sidhu, Gursimran; Shin, Kyungsup; Hahm, Eason; Huang, George X.; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Arany, Praveen R.; Weaver, James; Mooney, David J.] Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Arany, Praveen R.; Shin, Kyungsup] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Arany, Praveen R.] Leder Human Biol & Translat Med, Boston, MA 02115 USA. [Arany, Praveen R.; Cho, Andrew; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. [Chen, Aaron Chih-Hao; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Padwa, Bonnie L.] Childrens Hosp, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Barcellos-Hoff, Mary Helen] NYU, Sch Med, New York, NY 10016 USA. RP Mooney, DJ (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM mooneyd@seas.harvard.edu OI Barcellos-Hoff, Mary Helen/0000-0002-5994-9558 FU Harvard Presidential Scholarship; Wyss institute, Harvard Catalyst; Harvard Clinical and Translational Science Center [National Center for Research Resources (NCRR)]; National Center for Advancing Translational Sciences (NCATS); NIH [1UL1 TR001102-01]; Harvard University; [R37-DE-013349]; [R01-DE019023-01]; [R01-AI-050875]; [ZIA-DE-000698] FX R37-DE-013349 (D.J.M.), R01-DE019023-01, R01-AI-050875 (M.R.H.), ZIA-DE-000698 (A.B.K.), Harvard Presidential Scholarship (P.R.A.), Wyss institute, Harvard Catalyst, Harvard Clinical and Translational Science Center [National Center for Research Resources (NCRR) and National Center for Advancing Translational Sciences (NCATS), NIH, 1UL1 TR001102-01, and financial contributions from Harvard University and its affiliated academic health care centers], and the intramural research program, NIDCR, NIH (A.B.K. and P.R.A.). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the NIH. NR 45 TC 21 Z9 22 U1 0 U2 33 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 28 PY 2014 VL 6 IS 238 AR 238ra69 DI 10.1126/scitranslmed.3008234 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AI2DZ UT WOS:000336668900002 PM 24871130 ER PT J AU Hochberg, LR Cudkowicz, ME AF Hochberg, Leigh R. Cudkowicz, Merit E. TI Locked in, but not out? SO NEUROLOGY LA English DT Editorial Material ID BRAIN-COMPUTER INTERFACE; IN SYNDROME; CONSCIOUSNESS; DISORDERS; TETRAPLEGIA C1 [Hochberg, Leigh R.; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurotechnol Trials Unit,Dept Neurol, Boston, MA 02163 USA. [Hochberg, Leigh R.; Cudkowicz, Merit E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trial Inst,Dept Neurol, Boston, MA USA. [Hochberg, Leigh R.] US Dept Vet Affairs, Ctr Neurorestorat & Neurotechnol, Rehabil Res & Dev Serv, Off Res & Dev, Providence, RI USA. Brown Univ, Sch Engn, Providence, RI 02912 USA. Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. RP Hochberg, LR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurotechnol Trials Unit,Dept Neurol, Boston, MA 02163 USA. EM lhochberg@partners.org FU NIDCD NIH HHS [R01DC009899, R01 DC009899] NR 14 TC 4 Z9 4 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAY 27 PY 2014 VL 82 IS 21 BP 1852 EP 1853 DI 10.1212/WNL.0000000000000460 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA AQ5BM UT WOS:000342817600007 PM 24789868 ER PT J AU Ryu, SY Coutu, JP Rosas, HD Salat, DH AF Ryu, Seon Young Coutu, Jean-Philippe Rosas, H. Diana Salat, David H. TI Effects of insulin resistance on white matter microstructure in middle-aged and older adults SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; PLASMA-INSULIN; HUMAN BRAIN; RISK; ABNORMALITIES; DEGENERATION; METABOLISM; GENOTYPE; GLUCOSE AB Objective: To investigate the potential relationship between insulin resistance (IR) and white matter (WM) microstructure using diffusion tensor imaging in cognitively healthy middle-aged and older adults. Methods: Diffusion tensor imaging was acquired from 127 individuals (age range 41-86 years). IR was evaluated by the homeostasis model assessment of IR (HOMA-IR). Participants were divided into 2 groups based on HOMA-IR values: "high HOMA-IR" (>= 2.5, n= 27) and "low HOMA-IR" (<2.5, n=100). Cross-sectional voxel-based comparisons were performed using Tract-Based Spatial Statistics and anatomically defined regions of interest analysis. Results: The high HOMA-IR group demonstrated decreased axial diffusivity broadly throughout the cerebral WM in areas such as the corpus callosum, corona radiata, cerebral peduncle, posterior thalamic radiation, and right superior longitudinal fasciculus, and WM underlying the frontal, parietal, and temporal lobes, as well as decreased fractional anisotropy in the body and genu of corpus callosum and parts of the superior and anterior corona radiata, compared with the low HOMA-IR group, independent of age, WM signal abnormality volume, and antihypertensive medication status. These regions additionally demonstrated linear associations between diffusion measures and HOMA-IR across all subjects, with higher HOMA-IR values being correlated with lower axial diffusivity. Conclusions: In generally healthy adults, greater IR is associated with alterations in WM tissue integrity. These cross-sectional findings suggest that IR contributes to WM microstructural alterations in middle-aged and older adults. C1 [Ryu, Seon Young] Catholic Univ Korea, Coll Med, Daejeon St Marys Hosp, Dept Neurol, Seoul, South Korea. [Ryu, Seon Young; Coutu, Jean-Philippe; Rosas, H. Diana; Salat, David H.] Harvard Univ, Sch Med, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Massachus, Boston, MA 02115 USA. [Rosas, H. Diana] Harvard Univ, Sch Med, Dept Neurol, Athinoula A Martinos Ctr Biomed Imaging,Massachus, Boston, MA 02115 USA. [Coutu, Jean-Philippe] MIT, Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Salat, David H.] VA Boston Healthcare Syst, Boston, MA USA. RP Ryu, SY (reprint author), Catholic Univ Korea, Coll Med, Daejeon St Marys Hosp, Dept Neurol, Seoul, South Korea. EM streamline@catholic.ac.kr OI /0000-0003-4895-5642 FU NIH/NINR [R01NR10827, R01NS42861]; Biomedical Technology Program of the National Center for Research Resources (NCRR), NIH; NCRR [S10RR021110, S10RR023401, S10RR019307, S10RR019254, S10RR023043]; Advanced Multimodal Neuroimaging Training Program at MGH/HST Athinoula A. Martinos Center for Biomedical Imaging [2T90DA022759]; Fonds de Recherche du Quebec-Sante FX Supported by NIH/NINR: R01NR10827, R01NS42861. The authors thank the Athinoula A. Martinos Center for Biomedical Imaging, MGH, where this study was performed, and acknowledge the use of resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), NIH, as well as instrumentation obtained through the support of NCRR Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grants S10RR021110, S10RR023401, S10RR019307, S10RR019254, and S10RR023043. The authors also thank the Advanced Multimodal Neuroimaging Training Program (2T90DA022759; principal investigator Bruce Rosen) at the MGH/HST Athinoula A. Martinos Center for Biomedical Imaging and the Fonds de Recherche du Quebec-Sante, which supported J.-P.C. NR 38 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD MAY 27 PY 2014 VL 82 IS 21 BP 1862 EP 1870 DI 10.1212/WNL.0000000000000452 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA AQ5BM UT WOS:000342817600010 PM 24771537 ER PT J AU Zhao, X Chen, F Feng, ZJ Li, XS Zhou, XH AF Zhao, Xing Chen, Fei Feng, Zijian Li, Xiaosong Zhou, Xiao-Hua TI Characterizing the effect of temperature fluctuation on the incidence of malaria: an epidemiological study in south-west China using the varying coefficient distributed lag non-linear model SO MALARIA JOURNAL LA English DT Article ID DENGUE VIRUS TRANSMISSION; EAST-AFRICAN HIGHLANDS; METEOROLOGICAL FACTORS; YUNNAN PROVINCE; SPATIOTEMPORAL DISTRIBUTION; PLASMODIUM-FALCIPARUM; CLIMATE-CHANGE; AEDES-AEGYPTI; ASSOCIATION; RISK AB Background: Malaria transmission is strongly determined by the environmental temperature and the environment is rarely constant. Therefore, mosquitoes and parasites are not only exposed to the mean temperature, but also to daily temperature variation. Recently, both theoretical and laboratory work has shown, in addition to mean temperatures, daily fluctuations in temperature can affect essential mosquito and parasite traits that determine malaria transmission intensity. However, so far there is no epidemiological evidence at the population level to this problem. Methods: Thirty counties in southwest China were selected, and corresponding weekly malaria cases and weekly meteorological variables were collected from 2004 to 2009. Particularly, maximum, mean and minimum temperatures were collected. The daily temperature fluctuation was measured by the diurnal temperature range (DTR), the difference between the maximum and minimum temperature. The distributed lag non-linear model (MDLNM) was used to study the correlation between weekly malaria incidences and weekly mean temperatures, and the correlation pattern was allowed to vary over different levels of daily temperature fluctuations. Results: The overall non-linear patterns for mean temperatures are distinct across different levels of DTR. When under cooler temperature conditions, the larger mean temperature effect on malaria incidences is found in the groups of higher DTR, suggesting that large daily temperature fluctuations act to speed up the malaria incidence in cooler environmental conditions. In contrast, high daily fluctuations under warmer conditions will lead to slow down the mean temperature effect. Furthermore, in the group of highest DTR, 24-25 degrees C or 21-23 degrees C are detected as the optimal temperature for the malaria transmission. Conclusion: The environment is rarely constant, and the result highlights the need to consider temperature fluctuations as well as mean temperatures, when trying to understand or predict malaria transmission. This work may be the first epidemiological study confirming that the effect of the mean temperature depends on temperature fluctuations, resulting in relevant evidence at the population level. C1 [Zhao, Xing; Chen, Fei; Li, Xiaosong] Sichuan Univ, West China Sch Publ Hlth, Chengdu 610041, Peoples R China. [Zhao, Xing; Zhou, Xiao-Hua] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Feng, Zijian] Chinese Ctr Dis Control & Prevent, Off Dis Control & Emergency Response, Beijing 102206, Peoples R China. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98101 USA. RP Li, XS (reprint author), Sichuan Univ, West China Sch Publ Hlth, 17 Sect 3,South Renmin Rd, Chengdu 610041, Peoples R China. EM lixiaosong1101@126.com; azhou@u.washington.edu FU Natural Science Foundation of China, China Scholarship Council [30571618] FX The three reviewers' comments have greatly improved the content and readability of the manuscript. The Figure in the Additional file 1 was reproduced from a previous article written by same authors [35], and the Figure was included for the purpose of completeness. In addition, Table 1, with some new data, was partly reproduced from that previous article. This study was supported by the Natural Science Foundation of China (No. 30571618), China Scholarship Council (http://en.csc.edu.cn/). NR 45 TC 5 Z9 5 U1 2 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD MAY 27 PY 2014 VL 13 AR 192 DI 10.1186/1475-2875-13-192 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA AL2JC UT WOS:000338950900003 PM 24886630 ER PT J AU Carreras, ET Mega, JL AF Carreras, Edward T. Mega, Jessica L. TI Dual Antiplatelet Therapy for Heart Disease SO CIRCULATION LA English DT Editorial Material C1 [Carreras, Edward T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Internal Med, Boston, MA 02115 USA. [Mega, Jessica L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. RP Mega, JL (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM jmega@partners.org NR 2 TC 3 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAY 27 PY 2014 VL 129 IS 21 BP E506 EP E508 DI 10.1161/CIRCULATIONAHA.113.004305 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA AI9SR UT WOS:000337277000002 PM 24868000 ER PT J AU Kleijn, A Kloezeman, J Treffers-Westerlaken, E Fulci, G Leenstra, S Dirven, C Debets, R Lamfers, M AF Kleijn, Anne Kloezeman, Jenneke Treffers-Westerlaken, Elike Fulci, Giulia Leenstra, Sieger Dirven, Clemens Debets, Reno Lamfers, Martine TI The In Vivo Therapeutic Efficacy of the Oncolytic Adenovirus Delta24-RGD Is Mediated by Tumor-Specific Immunity SO PLOS ONE LA English DT Article ID CONDITIONALLY REPLICATIVE ADENOVIRUS; VESICULAR STOMATITIS-VIRUS; PHASE I/II TRIAL; INFLAMMATORY RESPONSE; ANTITUMOR IMMUNITY; MALIGNANT GLIOMAS; CANCER-PATIENTS; CELL-DEATH; GLIOBLASTOMA; VECTORS AB The oncolytic adenovirus Delta24-RGD represents a new promising therapeutic agent for patients with a malignant glioma and is currently under investigation in clinical phase I/II trials. Earlier preclinical studies showed that Delta24-RGD is able to effectively lyse tumor cells, yielding promising results in various immune-deficient glioma models. However, the role of the immune response in oncolytic adenovirus therapy for glioma has never been explored. To this end, we assessed Delta24-RGD treatment in an immune-competent orthotopic mouse model for glioma and evaluated immune responses against tumor and virus. Delta24-RGD treatment led to long-term survival in 50% of mice and this effect was completely lost upon administration of the immunosuppressive agent dexamethasone. Delta24-RGD enhanced intra-tumoral infiltration of F4/80+ macrophages, CD4+ and CD8+ T-cells, and increased the local production of pro-inflammatory cytokines and chemokines. In treated mice, T cell responses were directed to the virus as well as to the tumor cells, which was reflected in the presence of protective immunological memory in mice that underwent tumor rechallenge. Together, these data provide evidence that the immune system plays a vital role in the therapeutic efficacy of oncolytic adenovirus therapy of glioma, and may provide angles to future improvements on Delta24-RGD therapy. C1 [Kleijn, Anne; Kloezeman, Jenneke; Leenstra, Sieger; Dirven, Clemens; Lamfers, Martine] ErasmusMC, Dept Neurosurg, Brain Tumor Ctr, Rotterdam, Netherlands. [Treffers-Westerlaken, Elike; Debets, Reno] ErasmusMC, Dept Med Oncol, Lab Expt Tumor Immunol, Rotterdam, Netherlands. [Fulci, Giulia] Massachusetts Gen Hosp, Dept Neurosurg, Mol Neurosurg Lab, Brain Tumor Res Ctr, Boston, MA 02114 USA. RP Lamfers, M (reprint author), ErasmusMC, Dept Neurosurg, Brain Tumor Ctr, Rotterdam, Netherlands. EM m.lamfers@erasmusmc.nl RI Lamfers, Martine/C-6246-2016; OI Lamfers, Martine/0000-0001-7745-9029 NR 54 TC 9 Z9 9 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 27 PY 2014 VL 9 IS 5 AR e97495 DI 10.1371/journal.pone.0097495 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5NG UT WOS:000336914100014 PM 24866126 ER PT J AU McCormick, AW Abuelezam, NN Rhode, ER Hou, TG Walensky, RP Pei, PP Becker, JE DiLorenzo, MA Losina, E Freedberg, KA Lipsitch, M Seage, GR AF McCormick, Alethea W. Abuelezam, Nadia N. Rhode, Erin R. Hou, Taige Walensky, Rochelle P. Pei, Pamela P. Becker, Jessica E. DiLorenzo, Madeline A. Losina, Elena Freedberg, Kenneth A. Lipsitch, Marc Seage, George R., III TI Development, Calibration and Performance of an HIV Transmission Model Incorporating Natural History and Behavioral Patterns: Application in South Africa SO PLOS ONE LA English DT Article ID RESOURCE-LIMITED SETTINGS; ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED-CONTROLLED-TRIAL; SEXUAL RISK BEHAVIOR; DRUG-RESISTANT HIV; COST-EFFECTIVENESS; POTENTIAL IMPACT; UNITED-STATES; COTE-DIVOIRE; MATHEMATICAL-MODELS AB Understanding HIV transmission dynamics is critical to estimating the potential population-wide impact of HIV prevention and treatment interventions. We developed an individual-based simulation model of the heterosexual HIV epidemic in South Africa and linked it to the previously published Cost-Effectiveness of Preventing AIDS Complications (CEPAC) International Model, which simulates the natural history and treatment of HIV. In this new model, the CEPAC Dynamic Model (CDM), the probability of HIV transmission per sexual encounter between short-term, long-term and commercial sex worker partners depends upon the HIV RNA and disease stage of the infected partner, condom use, and the circumcision status of the uninfected male partner. We included behavioral, demographic and biological values in the CDM and calibrated to HIV prevalence in South Africa pre-antiretroviral therapy. Using a multi-step fitting procedure based on Bayesian melding methodology, we performed 264,225 simulations of the HIV epidemic in South Africa and identified 3,750 parameter sets that created an epidemic and had behavioral characteristics representative of a South African population pre-ART. Of these parameter sets, 564 contributed 90% of the likelihood weight to the fit, and closely reproduced the UNAIDS HIV prevalence curve in South Africa from 1990-2002. The calibration was sensitive to changes in the rate of formation of short-duration partnerships and to the partnership acquisition rate among high-risk individuals, both of which impacted concurrency. Runs that closely fit to historical HIV prevalence reflect diverse ranges for individual parameter values and predict a wide range of possible steady-state prevalence in the absence of interventions, illustrating the value of the calibration procedure and utility of the model for evaluating interventions. This model, which includes detailed behavioral patterns and HIV natural history, closely fits HIV prevalence estimates. C1 [McCormick, Alethea W.; Abuelezam, Nadia N.; Lipsitch, Marc; Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rhode, Erin R.; Hou, Taige; Walensky, Rochelle P.; Pei, Pamela P.; Becker, Jessica E.; DiLorenzo, Madeline A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Rhode, Erin R.; Hou, Taige; Walensky, Rochelle P.; Pei, Pamela P.; Becker, Jessica E.; DiLorenzo, Madeline A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Rhode, Erin R.; Hou, Taige; Walensky, Rochelle P.; Pei, Pamela P.; Becker, Jessica E.; DiLorenzo, Madeline A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA. [Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP McCormick, AW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM amccormi@hsph.harvard.edu RI Barley, Kamal/F-9579-2011 OI Barley, Kamal/0000-0003-1874-9813 FU [RO1-AI-058736]; [RO1-MH-087326]; [T32-AI-007535]; [T32-AI-007433] FX This work was funded by the following grants: RO1-AI-058736, RO1-MH-087326, T32-AI-007535 and T32-AI-007433. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 102 TC 3 Z9 3 U1 3 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 27 PY 2014 VL 9 IS 5 AR e98272 DI 10.1371/journal.pone.0098272 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5NG UT WOS:000336914100044 PM 24867402 ER PT J AU Nandi, B Pai, C Huang, Q Prabhala, RH Munshi, NC Gold, JS AF Nandi, Bisweswar Pai, Christine Huang, Qin Prabhala, Rao H. Munshi, Nikhil C. Gold, Jason S. TI CCR6, the Sole Receptor for the Chemokine CCL20, Promotes Spontaneous Intestinal Tumorigenesis SO PLOS ONE LA English DT Article ID INFLAMMATORY PROTEIN 3-ALPHA; COLORECTAL-CANCER; APC(MIN/+) MICE; EXPRESSION LEVEL; TUMOR-GROWTH; CELLS; MACROPHAGES; METASTASIS; TH17; PROLIFERATION AB Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been associated with colorectal cancer growth and metastasis, however, a causal role for CCL20 signaling through CCR6 in promoting intestinal carcinogenesis has not been demonstrated in vivo. In this study, we aimed to determine the role of CCL20-CCR6 interactions in spontaneous intestinal tumorigenesis. CCR6-deficient mice were crossed with mice heterozygous for a mutation in the adenomatous polyposis coli (APC) gene (APC(MIN/+) mice) to generate APC(MIN/+) mice with CCR6 knocked out (CCR6KO-APC(MIN/+) mice). CCR6KO-APC(MIN/+) mice had diminished spontaneous intestinal tumorigenesis. CCR6KO-APC(MIN/+) also had normal sized spleens as compared to the enlarged spleens found in APC(MIN/+) mice. Decreased macrophage infiltration into intestinal adenomas and non-tumor epithelium was observed in CCR6KO-APC(MIN/+) as compared to APC(MIN/+) mice. CCL20 signaling through CCR6 caused increased production of CCL20 by colorectal cancer cell lines. Furthermore, CCL20 had a direct mitogenic effect on colorectal cancer cells. Thus, interactions between CCL20 and CCR6 promote intestinal carcinogenesis. Our results suggest that the intestinal tumorigenesis driven by CCL20-CCR6 interactions may be driven by macrophage recruitment into the intestine as well as proliferation of neoplastic epithelial cells. This interaction could be targeted for the treatment or prevention of malignancy. C1 [Nandi, Bisweswar; Pai, Christine; Prabhala, Rao H.] VA Boston Healthcare Syst, Res Serv, West Roxbury, MA USA. [Nandi, Bisweswar; Huang, Qin; Prabhala, Rao H.; Munshi, Nikhil C.; Gold, Jason S.] Harvard Univ, Sch Med, Boston, MA 02138 USA. [Huang, Qin] VA Boston Healthcare Syst, Serv, Pathol, West Roxbury, MA USA. [Prabhala, Rao H.; Munshi, Nikhil C.] Dana Farber Canc Ctr, Boston, MA USA. [Munshi, Nikhil C.] VA Boston Healthcare Syst, Med Serv, West Roxbury, MA USA. [Gold, Jason S.] VA Boston Healthcare Syst, Surg Serv, West Roxbury, MA USA. [Gold, Jason S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Gold, JS (reprint author), Harvard Univ, Sch Med, Boston, MA 02138 USA. EM jgold4@partners.org RI Gold, Jason/O-5112-2014 OI Gold, Jason/0000-0002-2925-4755 FU Department of Veterans Affairs Office of Research and Development FX This work is supported by the Department of Veterans Affairs Office of Research and Development through a Career Development Award-2 to JSG. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 14 Z9 14 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 27 PY 2014 VL 9 IS 5 AR e97566 DI 10.1371/journal.pone.0097566 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AI5NG UT WOS:000336914100017 PM 24866282 ER PT J AU Wan, LX Tan, MJ Yang, J Inuzuka, H Dai, XP Wu, T Liu, J Shaik, S Chen, GA Deng, J Malumbres, M Letai, A Kirschner, MW Sun, Y Wei, WY AF Wan, Lixin Tan, Mingjia Yang, Jie Inuzuka, Hiroyuki Dai, Xiangpeng Wu, Tao Liu, Jia Shaik, Shavali Chen, Guoan Deng, Jing Malumbres, Marcos Letai, Anthony Kirschner, Marc W. Sun, Yi Wei, Wenyi TI APC(Cdc20) Suppresses Apoptosis through Targeting Bim for Ubiquitination and Destruction SO DEVELOPMENTAL CELL LA English DT Article ID ANAPHASE-PROMOTING COMPLEX; CANCER THERAPEUTIC TARGET; BCL-2 FAMILY-MEMBERS; SPINDLE CHECKPOINT; CELL-DEATH; MITOTIC EXIT; BH3 DOMAINS; BETA-TRCP; CDC20; DEGRADATION AB Anaphase-promoting complex Cdc20 (APC(Cdc20)) plays pivotal roles in governing mitotic progression. By suppressing APC(Cdc20), antimitotic agents activate the spindle-assembly checkpoint and induce apoptosis after prolonged treatment, whereas depleting endogenous Cdc20 suppresses tumorigenesis in part by triggering mitotic arrest and subsequent apoptosis. However, the molecular mechanism(s) underlying apoptosis induced by Cdc20 abrogation remains poorly understood. Here, we report the BH3-only proapoptotic protein Bim as an APC(Cdc20) target, such that depletion of Cdc20 sensitizes cells to apoptotic stimuli. Strikingly, Cdc20 and multiple APC-core components were identified in a small interfering RNA screen that, upon knockdown, sensitizes otherwise resistant cancer cells to chemoradiation in a Bim-dependent manner. Consistently, human adult T cell leukemia cells that acquire elevated APC(Cdc20) activity via expressing the Tax viral oncoprotein exhibit reduced Bim levels and resistance to anticancer agents. These results reveal an important role for APC(Cdc20) in governing apoptosis, strengthening the rationale for developing specific Cdc20 inhibitors as effective anticancer agents. C1 [Wan, Lixin; Inuzuka, Hiroyuki; Dai, Xiangpeng; Liu, Jia; Shaik, Shavali; Wei, Wenyi] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tan, Mingjia; Yang, Jie; Sun, Yi] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Yang, Jie] Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Shanghai 200025, Peoples R China. [Wu, Tao; Kirschner, Marc W.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Liu, Jia] Xi An Jiao Tong Univ, Inst Mitochondrial Biol & Med, Sch Life Sci & Technol, Xian 710049, Shaanxi, Peoples R China. [Chen, Guoan] Univ Michigan, Ann Arbor, MI 48109 USA. [Deng, Jing; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Malumbres, Marcos] Spanish Natl Canc Res Ctr CNIO, Cell Div, Madrid 28029, Spain. [Malumbres, Marcos] Spanish Natl Canc Res Ctr CNIO, Canc Grp, Madrid 28029, Spain. RP Wei, WY (reprint author), Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM wwei2@bidmc.harvard.edu FU NIH [GM089763, GM094777, CA118762, CA156744, GM39023]; Lady Tata Memorial Trust International Award for Research in Leukemia; University of Michigan Comprehensive Cancer Center FX We thank members of the Wei laboratory for critical reading of the manuscript; Roya Khosravi-Far, Gutian Xiao, Christophe P. Nicot, Peter Jackson, Matthew Meyerson, William Hahn, Frederic D. Sigoillot, and Randall W. King for providing reagents; and Timothy J. Mitchison, Randall W. King, and Susan E. Morgan-Lappe for helpful suggestions. W. W. is a Leukemia and Lymphoma Society Scholar and ACS Research Scholar. This work was supported in part by NIH grants GM089763 and GM094777 to W. W., CA118762 and CA156744 to Y.S., and GM39023 to M. W. K. L. W. was supported by the Lady Tata Memorial Trust International Award for Research in Leukemia. This work was also partially supported by a research grant from University of Michigan Comprehensive Cancer Center to Y.S. NR 45 TC 30 Z9 32 U1 4 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD MAY 27 PY 2014 VL 29 IS 4 BP 377 EP 391 DI 10.1016/j.devcel.2014.04.022 PG 15 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA AI1KA UT WOS:000336608600003 PM 24871945 ER PT J AU Carroll, KJ Esain, V Garnaas, MK Cortes, M Dovey, MC Nissim, S Frechette, GM Liu, SY Kwan, W Cutting, CC Harris, JM Gorelick, DA Halpern, ME Lawson, ND Goessling, W North, TE AF Carroll, Kelli J. Esain, Virginie Garnaas, Maija K. Cortes, Mauricio Dovey, Michael C. Nissim, Sahar Frechette, Gregory M. Liu, Sarah Y. Kwan, Wanda Cutting, Claire C. Harris, James M. Gorelick, Daniel A. Halpern, Marnie E. Lawson, Nathan D. Goessling, Wolfram North, Trista E. TI Estrogen Defines the Dorsal-Ventral Limit of VEGF Regulation to Specify the Location of the Hemogenic Endothelial Niche SO DEVELOPMENTAL CELL LA English DT Article ID HEMATOPOIETIC STEM-CELLS; RECEPTOR-BETA; GROWTH-FACTOR; VENOUS PROGENITORS; AORTIC ENDOTHELIUM; NORMAL-PREGNANCY; IN-VIVO; ZEBRAFISH; NOTCH; PATHWAY AB Genetic control of hematopoietic stem and progenitor cell (HSPC) function is increasingly understood; however, less is known about the interactions specifying the embryonic hematopoietic niche. Here, we report that 17 beta-estradiol (E2) influences production of runx1+ HSPCs in the AGM region by antagonizing VEGF signaling and subsequent assignment of hemogenic endothelial (HE) identity. Exposure to exogenous E2 during vascular niche development significantly disrupted flk1+ vessel maturation, ephrinB2+ arterial identity, and specification of scl+ HE by decreasing expression of VEGFAa and downstream arterial Notch-pathway components; heat shock induction of VEGFAa/Notch rescued E2-mediated hematovascular defects. Conversely, repression of endogenous E2 activity increased somitic VEGF expression and vascular target regulation, shifting assignment of arterial/venous fate and HE localization; blocking E2 signaling allowed venous production of scl+/runx1+ cells, independent of arterial identity acquisition. Together, these data suggest that yolk-derived E2 sets the ventral boundary of hemogenic vascular niche specification by antagonizing the dorsal-ventral regulatory limits of VEGF. C1 [Carroll, Kelli J.; Esain, Virginie; Cortes, Mauricio; Dovey, Michael C.; Frechette, Gregory M.; Liu, Sarah Y.; Kwan, Wanda; Harris, James M.; North, Trista E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Garnaas, Maija K.; Nissim, Sahar; Cutting, Claire C.; Goessling, Wolfram] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Goessling, Wolfram] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gorelick, Daniel A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Halpern, Marnie E.] Carnegie Inst Sci, Baltimore, MD 21218 USA. [Lawson, Nathan D.] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Goessling, Wolfram; North, Trista E.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Goessling, W (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. EM wgoessling@partners.org; tnorth@bidmc.harvard.edu OI Goessling, Wolfram/0000-0001-9972-1569 FU American Society of Hematology Scholar Award; National Institute of Environmental Health Sciences [R21]; National Science Foundation Graduate Research Fellowship; Harvard University Vranos Family Graduate Research Fellowship FX We thank P. Crosier and K. Crosier for the runx1P1:eGFP line, S. W. Jin for the hs:VEGFAa line, and B. Paw, I. Drummond, C. Burns, and M. Lin for suggestions and reagents. This investigation was supported by an American Society of Hematology Scholar Award and a National Institute of Environmental Health Sciences R21 (to T.E.N.). K.J.C. is supported by a National Science Foundation Graduate Research Fellowship and a Harvard University Vranos Family Graduate Research Fellowship. NR 64 TC 4 Z9 4 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 EI 1878-1551 J9 DEV CELL JI Dev. Cell PD MAY 27 PY 2014 VL 29 IS 4 BP 437 EP 453 DI 10.1016/j.devcel.2014.04.012 PG 17 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA AI1KA UT WOS:000336608600007 PM 24871948 ER PT J AU Muller, E White, S Delmonico, F AF Muller, Elmi White, Sarah Delmonico, Francis TI Regional Perspective: Developing Organ Transplantation in Sub-Saharan Africa SO TRANSPLANTATION LA English DT Editorial Material DE Developing countries/Africa C1 [Muller, Elmi] Univ Cape Town, Groote Schuur Hosp, Dept Surg, ZA-7925 Cape Town, South Africa. [White, Sarah] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Delmonico, Francis] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Muller, E (reprint author), Groote Schuur Hosp, Dept Surg, Main Rd, ZA-7925 Cape Town, South Africa. EM elmi.muller@uct.ac.za RI Muller, Elmi/I-3258-2014 OI Muller, Elmi/0000-0003-4891-5296 NR 1 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD MAY 27 PY 2014 VL 97 IS 10 BP 975 EP 976 DI 10.1097/TP.0000000000000144 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA AI3FL UT WOS:000336745900006 PM 24770622 ER PT J AU Lassen, KG Kuballa, P Conway, KL Patel, KK Becker, CE Peloquin, JM Villablanca, EJ Norman, JM Liu, TC Heath, RJ Becker, ML Fagbami, L Horn, H Mercer, J Yilmaz, OH Jaffe, JD Shamji, AF Bhan, AK Carr, SA Daly, MJ Virgin, HW Schreiber, SL Stappenbeck, TS Xavier, RJ AF Lassen, Kara G. Kuballa, Petric Conway, Kara L. Patel, Khushbu K. Becker, Christine E. Peloquin, Joanna M. Villablanca, Eduardo J. Norman, Jason M. Liu, Ta-Chiang Heath, Robert J. Becker, Morgan L. Fagbami, Lola Horn, Heiko Mercer, Johnathan Yilmaz, Omer H. Jaffe, Jacob D. Shamji, Alykhan F. Bhan, Atul K. Carr, Steven A. Daly, Mark J. Virgin, Herbert W. Schreiber, Stuart L. Stappenbeck, Thaddeus S. Xavier, Ramnik J. TI Atg16L1 T300A variant decreases selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; PANETH CELLS; SUSCEPTIBILITY LOCI; GENE ATG16L1; PATHOGENESIS; PHENOTYPES; REVEALS; NOD2 AB A coding polymorphism (Thr300Ala) in the essential autophagy gene, autophagy related 16-like 1 (ATG16L1), confers increased risk for the development of Crohn disease, although the mechanisms by which single disease-associated polymorphisms contribute to pathogenesis have been difficult to dissect given that environmental factors likely influence disease initiation in these patients. Here we introduce a knock-in mouse model expressing the Atg16L1 T300A variant. Consistent with the human polymorphism, T300A knock-in mice do not develop spontaneous intestinal inflammation, but exhibit morphological defects in Paneth and goblet cells. Selective autophagy is reduced in multiple cell types from T300A knock-in mice compared with WT mice. The T300A polymorphism significantly increases caspase 3- and caspase 7-mediated cleavage of Atg16L1, resulting in lower levels of full-length Atg16Ll T300A protein. Moreover, Atg16L1 T300A is associated with decreased antibacterial autophagy and increased IL-1 beta production in primary cells and in vivo. Quantitative proteomics for protein interactors of ATG16L1 identified previously unknown nonoverlapping sets of proteins involved in ATG16L1-dependent antibacterial autophagy or IL-1 beta production. These findings demonstrate how the T300A polymorphism leads to cell type- and pathway-specific disruptions of selective autophagy and suggest a mechanism by which this polymorphism contributes to disease. C1 [Lassen, Kara G.; Kuballa, Petric; Conway, Kara L.; Villablanca, Eduardo J.; Heath, Robert J.; Fagbami, Lola; Horn, Heiko; Mercer, Johnathan; Jaffe, Jacob D.; Carr, Steven A.; Daly, Mark J.; Xavier, Ramnik J.] Broad Inst, Cambridge, MA 02142 USA. [Lassen, Kara G.; Kuballa, Petric; Conway, Kara L.; Becker, Christine E.; Peloquin, Joanna M.; Villablanca, Eduardo J.; Heath, Robert J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Conway, Kara L.; Peloquin, Joanna M.; Villablanca, Eduardo J.; Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Patel, Khushbu K.; Norman, Jason M.; Liu, Ta-Chiang; Becker, Morgan L.; Virgin, Herbert W.; Stappenbeck, Thaddeus S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Horn, Heiko] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Yilmaz, Omer H.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Yilmaz, Omer H.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Yilmaz, Omer H.; Bhan, Atul K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shamji, Alykhan F.; Schreiber, Stuart L.] Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. [Bhan, Atul K.; Daly, Mark J.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Virgin, Herbert W.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RP Schreiber, SL (reprint author), Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA. EM stuart_schreiber@harvard.edu; xavier@molbio.mgh.harvard.edu OI Horn, Heiko/0000-0003-4898-0557; Villablanca, Eduardo/0000-0001-9522-9729 FU Leona M. and Harry B. Helmsley Charitable Trust; Crohn's and Colitis Foundation of America Genetics Initiative; National Institutes of Health [DK097485, DK043351, AI084887]; Deutsche Forschungsgemeinschaft [KU2511/1-1] FX We thank Natalia Nedelsky for editorial assistance and Brian Seed and Naifang Liu for help with the knock-in model design. This work was supported by the Leona M. and Harry B. Helmsley Charitable Trust, the Crohn's and Colitis Foundation of America Genetics Initiative, National Institutes of Health Grants DK097485 and DK043351 (to R.J.X.) and AI084887 (to T.S.S. and H.W.V.), and Deutsche Forschungsgemeinschaft Fellowship Award KU2511/1-1 (to P.K.). NR 37 TC 72 Z9 73 U1 1 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 27 PY 2014 VL 111 IS 21 BP 7741 EP 7746 DI 10.1073/pnas.1407001111 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH8TO UT WOS:000336411300057 PM 24821797 ER PT J AU Yi, TF Zhai, B Yu, YH Kiyotsugu, Y Raschle, T Etzkorn, M Seo, HC Nagiec, M Luna, RE Reinherz, EL Blenis, J Gygi, SP Wagner, G AF Yi, Tingfang Zhai, Bo Yu, Yonghao Kiyotsugu, Yoshikawa Raschle, Thomas Etzkorn, Manuel Seo, Hee-Chan Nagiec, Michal Luna, Rafael E. Reinherz, Ellis L. Blenis, John Gygi, Steven P. Wagner, Gerhard TI Quantitative phosphoproteomic analysis reveals system-wide signaling pathways downstream of SDF-1/CXCR4 in breast cancer stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemokine receptor; GPCR; MAPK ID PROTEIN-KINASE-A; MAP KINASE; IN-VIVO; PHOSPHORYLATION; IDENTIFICATION; ACTIVATION; NETWORKS; ISOFORMS; FAMILY AB Breast cancer is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.7 million new cases and 522,000 deaths around the world in 2012 alone. Cancer stem cells (CSCs) are essential for tumor reoccurrence and metastasis which is the major source of cancer lethality. G protein-coupled receptor chemokine (C-X-C motif) receptor 4 (CXCR4) is critical for tumor metastasis. However, stromal cell-derived factor 1 (SDF-1)/CXCR4-mediated signaling pathways in breast CSCs are largely unknown. Using isotope reductive dimethylation and large-scale MS-based quantitative phosphoproteome analysis, we examined protein phosphorylation induced by SDF-1/CXCR4 signaling in breast CSCs. We quantified more than 11,000 phosphorylation sites in 2,500 phosphoproteins. Of these phosphosites, 87% were statistically unchanged in abundance in response to SDF-1/CXCR4 stimulation. In contrast, 545 phosphosites in 266 phosphoproteins were significantly increased, whereas 113 phosphosites in 74 phosphoproteins were significantly decreased. SDF-1/CXCR4 increases phosphorylation in 60 cell migration-and invasion-related proteins, of them 43 (>70%) phosphoproteins are unrecognized. In addition, SDF-1/CXCR4 upregulates the phosphorylation of 44 previously uncharacterized kinases, 8 phosphatases, and 1 endogenous phosphatase inhibitor. Using computational approaches, we performed system-based analyses examining SDF-1/CXCR4-mediated phosphoproteome, including construction of kinase-substrate network and feedback regulation loops downstream of SDF-1/CXCR4 signaling in breast CSCs. We identified a previously unidentified SDF-1/CXCR4-PKA-MAP2K2-ERK signaling pathway and demonstrated the feedback regulation on MEK, ERK1/2, delta-catenin, and PPP1C alpha in SDF-1/CXCR4 signaling in breast CSCs. This study gives a system-wide view of phosphorylation events downstream of SDF-1/CXCR4 signaling in breast CSCs, providing a resource for the study of CSC-targeted cancer therapy. C1 [Yi, Tingfang; Raschle, Thomas; Etzkorn, Manuel; Seo, Hee-Chan; Luna, Rafael E.; Wagner, Gerhard] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhai, Bo; Yu, Yonghao; Nagiec, Michal; Blenis, John; Gygi, Steven P.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Kiyotsugu, Yoshikawa; Reinherz, Ellis L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Gygi, SP (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM steven_gygi@hms.harvard.edu; gerhard_wagner@hms.harvard.edu RI Etzkorn, Manuel/H-5042-2013 OI Etzkorn, Manuel/0000-0002-9796-3246 FU National Institutes of Health [CA068262] FX We thank Robert Weinberg of Whitehead Institute for Biomedical Research of Massachusetts Institute of Technology for the HMLER cell lines. This work was supported by funding from National Institutes of Health Grant CA068262 (to G.W.). NR 32 TC 31 Z9 34 U1 2 U2 25 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 MAY 27 PY 2014 VL 111 IS 21 BP E2182 EP E2190 DI 10.1073/pnas.1404943111 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH8TO UT WOS:000336411300007 PM 24782546 ER PT J AU Han, SH Cho, FH Song, YK Paulsen, J Song, YQ Kim, YR Kim, JK Cho, G Cho, H AF Han, S. H. Cho, F. H. Song, Y. K. Paulsen, J. Song, Y. Q. Kim, Y. R. Kim, J. K. Cho, G. Cho, H. TI Ultrafast 3D spin-echo acquisition improves Gadolinium-enhanced MRI signal contrast enhancement SO SCIENTIFIC REPORTS LA English DT Article ID MAGNETIC-RESONANCE; IMAGING TECHNIQUE; TRACER KINETICS; GRADIENT-ECHO; DYNAMIC MRI; DCE-MRI; K-SPACE; SEQUENCE; AGENTS; FLASH AB Long scan times of 3D volumetric MR acquisitions usually necessitate ultrafast in vivo gradient-echo acquisitions, which are intrinsically susceptible to magnetic field inhomogeneities. This is especially problematic for contrast-enhanced (CE)-MRI applications, where non-negligible T-2* effect of contrast agent deteriorates the positive signal contrast and limits the available range of MR acquisition parameters and injection doses. To overcome these shortcomings without degrading temporal resolution, ultrafast spin-echo acquisitions were implemented. Specifically, a multiplicative acceleration factor from multiple spin echoes (X32) and compressed sensing (CS) sampling (X8) allowed highly-accelerated 3D Multiple-Modulation-Multiple-Echo (MMME) acquisition. At the same time, the CE-MRI of kidney with Gd-DOTA showed significantly improved signal enhancement for CS-MMME acquisitions (X7) over that of corresponding FLASH acquisitions (X2). Increased positive contrast enhancement and highly accelerated acquisition of extended volume with reduced RF irradiations will be beneficial for oncological and nephrological applications, in which the accurate in vivo 3D quantification of contrast agent concentration is necessary with high temporal resolution. C1 [Han, S. H.; Cho, F. H.; Song, Y. K.; Cho, H.] UNIST, Dept Biomed Engn, Ulsan, South Korea. [Paulsen, J.; Song, Y. Q.] Schlumberger Doll Res Ctr, Cambridge, MA USA. [Kim, Y. R.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kim, J. K.] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol,Dept Radiol, Seoul, South Korea. [Cho, G.] Korea Basic Sci Inst, Ochang, South Korea. RP Cho, G (reprint author), Korea Basic Sci Inst, Ochang, South Korea. EM gyunggoo@kbsi.re.kr; hjcho@unist.ac.kr FU National Research Foundation of Korea (NRF) - Korean government [2010-0028684]; Future Challenge Research Fund of UNIST (Ulsan National Institute of Science and Technology) [1.130030.01] FX This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (No.2010-0028684). This work was also supported by the 2013 Future Challenge Research Fund (Project No. 1.130030.01) of UNIST (Ulsan National Institute of Science and Technology). NR 49 TC 1 Z9 1 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD MAY 27 PY 2014 VL 4 AR 5061 DI 10.1038/srep05061 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH8DO UT WOS:000336364500003 PM 24863102 ER PT J AU Khan, S Lefevre, J Baillet, S Michmizos, KP Ganesan, S Kitzbichler, MG Zetino, M Haemaelaeinen, M Papadelis, C Kenet, T AF Khan, Sheraz Lefevre, Julien Baillet, Sylvain Michmizos, Konstantinos P. Ganesan, Santosh Kitzbichler, Manfred G. Zetino, Manuel Haemaelaeinen, MattiS. Papadelis, Christos Kenet, Tal TI Encoding cortical dynamics in sparse features SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE motion field; optical flow; MEG source imaging; Helmholtz-Hodge decomposition; epilepsy ID TUBEROUS SCLEROSIS; OPTICAL-FLOW; FIELD DECOMPOSITION; LOCALIZATION; PROPAGATION; BRAIN; MEG; MAGNETOENCEPHALOGRAPHY; EPILEPSY; EEG AB Distributed cortical solutions of magnetoencephalography (MEG) and electroencephalography (EEG) exhibit complex spatial and temporal dynamics. The extraction of patterns of interest and dynamic features from these cortical signals has so far relied on the expertise of investigators. There is a definite need in both clinical and neuroscience research for a method that will extract critical features from high-dimensional neuroimaging data in an automatic fashion. We have previously demonstrated the use of optical flow techniques for evaluating the kinematic properties of motion field projected on non-flat manifolds like in a cortical surface. We have further extended this framework to automatically detect features in the optical flow vector field by using the modified and extended 2-Riemannian Helmholtz-Hodge decomposition (HHD). Here, we applied these mathematical models on simulation and MEG data recorded from a healthy individual during a somatosensory experiment and an epilepsy pediatric patient during sleep. We tested whether our technique can automatically extract salient dynamical features of cortical activity. Simulation results indicated that we can precisely reproduce the simulated cortical dynamics with HHD; encode them in sparse features and represent the propagation of brain activity between distinct cortical areas. Using HHD, we decoded the somatosensory N20 component into two HHD features and represented the dynamics of brain activity as a traveling source between two primary somatosensory regions. In the epilepsy patient, we displayed the propagation of the epileptic activity around the margins of a brain lesion. Our findings indicate that HHD measures computed from cortical dynamics can: (i) quantitatively access the cortical dynamics in both healthy and disease brain in terms of sparse features and dynamic brain activity propagation between distinct cortical areas, and (ii) facilitate a reproducible, automated analysis of experimental and clinical MEG/EEG source imaging data. C1 [Khan, Sheraz; Michmizos, Konstantinos P.; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Haemaelaeinen, MattiS.; Kenet, Tal] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Khan, Sheraz; Michmizos, Konstantinos P.] MIT, McGovern Inst, Cambridge, MA 02139 USA. [Khan, Sheraz; Michmizos, Konstantinos P.; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Kenet, Tal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Lefevre, Julien] Univ Toulon & Var, Aix Marseille Univ, CNRS, ENSAM LSIS UMR 7296, Marseille, France. [Baillet, Sylvain] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Kitzbichler, Manfred G.] Univ Cambridge, Behav & Clin Neurosci Inst, Cambridge, England. [Papadelis, Christos] Harvard Univ, Sch Med, Boston Childrens Hosp, Fetal Neonatal Neuroimaging & Dev Sci,BabyMEG Fac, Boston, MA USA. [Papadelis, Christos] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Newborn Med, Boston, MA USA. RP Khan, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIT,Athinoula A Martinos Ctr Biomed Imaging, 1115-Q,149 13th St, Charlestown, MA 02129 USA. EM sheraz@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; OI Khan, Sheraz/0000-0002-6792-3577 FU Nancy Lurie Marks Family Foundation; Simons Foundation; NIBIB [5R01EB009048]; Quebec Fund for Health Research; Natural Sciences and Engineering Research Council of Canada; [P41RR014075]; [NIH 2R01EB009048-05] FX This work was supported by the Nancy Lurie Marks Family Foundation (Sheraz Khan, Manfred G. Kitzbichler, Tal Kenet), Simons Foundation (Tal Kenet), NIBIB:5R01EB009048 (Matti S. Hamalainen), P41RR014075 (Matti S. Hamalainen), Senior-Scientist Salary Award from the Quebec Fund for Health Research (Sylvain Baillet), NIH 2R01EB009048-05 (Sylvain Baillet) and a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (Sylvain Baillet). NR 37 TC 2 Z9 2 U1 0 U2 7 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD MAY 23 PY 2014 VL 8 AR 338 DI 10.3389/fnhum.2014.00338 PG 9 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA AL9XX UT WOS:000339498000001 PM 24904377 ER PT J AU Liu, RJ Dai, ZY Yeager, M Irizarry, RA Ritchie, ME AF Liu, Ruijie Dai, Zhiyin Yeager, Meredith Irizarry, Rafael A. Ritchie, Matthew E. TI KRLMM: an adaptive genotype calling method for common and low frequency variants SO BMC BIOINFORMATICS LA English DT Article DE Genotyping; Clustering; Microarray data analysis ID GENOME-WIDE ASSOCIATION; ALGORITHM; POPULATION; BEADCHIPS; RARE; MAP AB Background: SNP genotyping microarrays have revolutionized the study of complex disease. The current range of commercially available genotyping products contain extensive catalogues of low frequency and rare variants. Existing SNP calling algorithms have difficulty dealing with these low frequency variants, as the underlying models rely on each genotype having a reasonable number of observations to ensure accurate clustering. Results: Here we develop KRLMM, a new method for converting raw intensities into genotype calls that aims to overcome this issue. Our method is unique in that it applies careful between sample normalization and allows a variable number of clusters k (1, 2 or 3) for each SNP, where k is predicted using the available data. We compare our method to four genotyping algorithms (GenCall, GenoSNP, Illuminus and OptiCall) on several Illumina data sets that include samples from the HapMap project where the true genotypes are known in advance. All methods were found to have high overall accuracy (> 98%), with KRLMM consistently amongst the best. At low minor allele frequency, the KRLMM, OptiCall and GenoSNP algorithms were observed to be consistently more accurate than GenCall and Illuminus on our test data. Conclusions: Methods that tailor their approach to calling low frequency variants by either varying the number of clusters (KRLMM) or using information from other SNPs (OptiCall and GenoSNP) offer improved accuracy over methods that do not (GenCall and Illuminus). The KRLMM algorithm is implemented in the open-source crlmm package distributed via the Bioconductor project (http://www.bioconductor.org). C1 [Liu, Ruijie; Dai, Zhiyin; Ritchie, Matthew E.] Walter & Eliza Hall Inst Med Res, Mol Med Div, Parkville, Vic 3052, Australia. [Yeager, Meredith] NCI Frederick, Canc Genom Res Lab, SAIC Frederick Inc, Frederick, MD 20877 USA. [Irizarry, Rafael A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Ritchie, Matthew E.] Univ Melbourne, Dept Math & Stat, Parkville, Vic 3010, Australia. [Ritchie, Matthew E.] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia. RP Irizarry, RA (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, CLSB 11007,450 Brookline Ave, Boston, MA 02215 USA. EM rafa@jimmy.harvard.edu; mritchie@wehi.edu.au OI Ritchie, Matthew/0000-0002-7383-0609 FU NHMRC [1050661]; Victorian State Government; Australian Government NHMRC IRIISS; NIH [R01GM083084] FX We thank Gordon Smyth for advice on regression analysis. This research was supported by NHMRC Project grant 1050661 (RL, MR), Victorian State Government Operational Infrastructure Support, Australian Government NHMRC IRIISS and NIH grant R01GM083084 (RI). NR 26 TC 0 Z9 0 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAY 23 PY 2014 VL 15 AR 158 DI 10.1186/1471-2105-15-158 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA AK2IS UT WOS:000338243300001 PM 24886250 ER PT J AU Kunchithapautham, K Atkinson, C Rohrer, B AF Kunchithapautham, Kannan Atkinson, Carl Rohrer, Baerbel TI Smoke Exposure Causes Endoplasmic Reticulum Stress and Lipid Accumulation in Retinal Pigment Epithelium through Oxidative Stress and Complement Activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UNFOLDED PROTEIN RESPONSE; FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; CIGARETTE-SMOKE; BRUCHS MEMBRANE; CHOROIDAL NEOVASCULARIZATION; REGULATORY PROTEINS; ALTERNATIVE PATHWAY; GEOGRAPHIC ATROPHY; APOLIPOPROTEIN-E AB Age-related macular degeneration (AMD) is a complex disease caused by genetic and environmental factors, including genetic variants in complement components and smoking. Smoke exposure leads to oxidative stress, complement activation, endoplasmic reticulum (ER) stress, and lipid dysregulation, which have all been proposed to be associated with AMD pathogenesis. Here we examine the effects of smoke exposure on the retinal pigment epithelium (RPE). Mice were exposed to cigarette smoke or filtered air for 6 months. RPE cells grown as stable monolayers were exposed to 5% cigarette smoke extract (CSE). Effects of smoke were determined by biochemical, molecular, and histological measures. Effects of the alternative pathway (AP) of complement and complement C3a anaphylatoxin receptor signaling were analyzed using knock-out mice or specific inhibitors. ER stress markers were elevated after smoke exposure in RPE of intact mice, which was eliminated in AP-deficient mice. To examine this relationship further, RPE monolayers were exposed to CSE. Short term smoke exposure resulted in production and release of complement C3, the generation of C3a, oxidative stress, complement activation on the cell membrane, and ER stress. Long term exposure to CSE resulted in lipid accumulation, and secretion. All measures were reversed by blocking C3a complement receptor (C3aR), alternative complement pathway signaling, and antioxidant therapy. Taken together, our results provide clear evidence that smoke exposure results in oxidative stress and complement activation via the AP, resulting in ER stress-mediated lipid accumulation, and further suggesting that oxidative stress and complement act synergistically in the pathogenesis of AMD. C1 [Kunchithapautham, Kannan; Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Atkinson, Carl] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Rohrer, Baerbel] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Rohrer, B (reprint author), 167 Ashley Ave, Charleston, SC 29425 USA. EM rohrer@musc.edu FU National Institutes of Health [C06RR015455] FX Animal studies were conducted in a facility constructed with support from the National Institutes of Health Grant C06RR015455. NR 78 TC 26 Z9 26 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 23 PY 2014 VL 289 IS 21 BP 14534 EP 14546 DI 10.1074/jbc.M114.564674 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA AI9JE UT WOS:000337248100012 PM 24711457 ER PT J AU Wang, J Lin, XQ Wang, S Wang, CF Wang, QX Duan, XK Lu, P Wang, Q Wang, CY Liu, XS Huang, JY AF Wang, Juan Lin, Xueqiu Wang, Su Wang, Chenfei Wang, Qixuan Duan, Xikun Lu, Peng Wang, Qian Wang, Chengyang Liu, X. Shirley Huang, Jinyan TI PHF8 and REST/NRSF co-occupy gene promoters to regulate proximal gene expression SO SCIENTIFIC REPORTS LA English DT Article ID LINKED MENTAL-RETARDATION; CLEFT LIP/CLEFT PALATE; HISTONE METHYLATION; LOCATION ANALYSIS; DEMETHYLASE PHF8; H3K4 DEMETHYLASE; NEURONAL GENES; TRANSCRIPTION; MUTATIONS; GENOME AB Chromatin regulators play an important role in the development of human diseases. In this study, we focused on Plant Homeo Domain Finger protein 8 (PHF8), a chromatin regulator that has attracted special concern recently. PHF8 is a histone lysine demethylase ubiquitously expressed in nuclei. Mutations of PHF8 are associated with X-linked mental retardation. It usually functions as a transcriptional co-activator by associating with H3K4me3 and RNA polymerase II. We found that PHF8 may associate with another regulator, REST/NRSF, predominately at promoter regions via studying several published PHF8 chromatin immunoprecipitation-sequencing (ChIP-Seq) datasets. Our analysis suggested that PHF8 not only activates but may also repress gene expression. C1 [Wang, Juan; Lin, Xueqiu; Wang, Su; Wang, Chenfei; Wang, Qixuan; Duan, Xikun; Wang, Qian; Wang, Chengyang; Huang, Jinyan] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. [Lu, Peng] Fudan Univ, ShanghaiMed Sch, Dept Environm Hlth, Yangpu, Peoples R China. [Liu, X. Shirley] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Huang, JY (reprint author), Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. EM jyhuang@tongji.edu.cn FU National Basic Reaserch Program of China (973 Programs) [2010CB944904]; National Natural Science Foundation of China [31329003] FX We thank group members for constructive comments. This project was supported by the National Basic Reaserch Program of China (973 Programs: 2010CB944904), the National Natural Science Foundation of China (31329003). NR 28 TC 1 Z9 1 U1 4 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD MAY 23 PY 2014 VL 4 AR 5008 DI 10.1038/srep05008 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA AH6TN UT WOS:000336263700001 PM 24852203 ER PT J AU Schwerdtfeger, K Wand, S Schmid, O Roessler, M Quintel, M Leissner, KB Russo, SG AF Schwerdtfeger, Katrin Wand, Saskia Schmid, Oliver Roessler, Markus Quintel, Michael Leissner, Kay B. Russo, Sebastian G. TI A prospective, blinded evaluation of a video-assisted '4-stage approach' during undergraduate student practical skills training SO BMC MEDICAL EDUCATION LA English DT Article DE Teaching methods; Medical students; Trauma care ID TEACHING TECHNIQUE; MEDICAL-EDUCATION; EMERGENCY AB Background: The 4-stage approach (4-SA) is used as a didactic method for teaching practical skills in international courses on resuscitation and the structured care of trauma patients. The aim of this study was to evaluate objective and subjective learning success of a video-assisted 4-SA in teaching undergraduate medical students. Methods: The participants were medical students learning the principles of the acute treatment of trauma patients in their multidiscipline course on emergency and intensive care medicine. The participants were quasi-randomly divided into two groups. The 4-SA was used in both groups. In the control group, all four steps were presented by an instructor. In the study group, the first two steps were presented as a video. At the end of the course a 5-minute objective, structured clinical examination (OSCE) of a simulated trauma patient was conducted. The test results were divided into objective results obtained through a checklist with 9 dichotomous items and the assessment of the global performance rated subjectively by the examiner on a Likert scale from 1 to 6. Results: 313 students were recruited; the results of 256 were suitable for analysis. The OSCE results were excellent in both groups and did not differ significantly (control group: median 9, interquantil range (IQR) 8-9, study group: median 9, IQR 8-9; p = 0.29). The global performance was rated significantly better for the study group (median 1, IQR 1-2 vs. median 2, IQR 1-3; p < 0.01). The relative knowledge increase, stated by the students in their evaluation after the course, was greater in the study group (85% vs. 80%). Conclusion: It is possible to employ video assistance in the classical 4-SA with comparable objective test results in an OSCE. The global performance was significantly improved with use of video assistance. C1 [Schwerdtfeger, Katrin; Wand, Saskia; Schmid, Oliver; Roessler, Markus; Quintel, Michael; Russo, Sebastian G.] Univ Hosp Gottingen, Dept Anaesthesiol, D-37075 Gottingen, Germany. [Leissner, Kay B.] VA Boston Healthcare Syst, Boston, MA USA. RP Russo, SG (reprint author), Univ Hosp Gottingen, Dept Anaesthesiol, D-37075 Gottingen, Germany. EM s.russo@medizin.uni-goettingen.de NR 14 TC 1 Z9 1 U1 2 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6920 J9 BMC MED EDUC JI BMC Med. Educ. PD MAY 22 PY 2014 VL 14 AR 104 DI 10.1186/1472-6920-14-104 PG 6 WC Education & Educational Research; Education, Scientific Disciplines SC Education & Educational Research GA AJ0AZ UT WOS:000337312600002 PM 24885140 ER PT J AU Sun, T Wang, X He, HH Sweeney, CJ Liu, SX Brown, M Balk, S Lee, GSM Kantoff, PW AF Sun, T. Wang, X. He, H. H. Sweeney, C. J. Liu, S. X. Brown, M. Balk, S. Lee, G-S M. Kantoff, P. W. TI MiR-221 promotes the development of androgen independence in prostate cancer cells via downregulation of HECTD2 and RAB1A SO ONCOGENE LA English DT Article DE microRNA; miR-221; castration resistant prostate cancer; androgen receptor signaling ID BREAST-CANCER; MESENCHYMAL TRANSITION; TAMOXIFEN RESISTANCE; RECEPTOR; EXPRESSION; GENES; PROGRESSION; CASTRATION; MICRORNAS; PROTEINS AB Hormone-sensitive prostate cancer typically progresses to castration resistant prostate cancer (CRPC) after the androgen deprivation therapy. We investigated the impact of microRNAs (miRs) in the transition of prostate cancer to CRPC. MiR-221/-222 was highly expressed in bone metastatic CRPC tumor specimens. We previously demonstrated that transient overexpression of miR-221/-222 in LNCaP promoted the development of the CRPC phenotype. In current study, we show that stably overexpressing miR-221 confers androgen independent (AI) cell growth in LNCaP by rescuing LNCaP cells from growth arrest at G1 phase due to the lack of androgen. Overexpressing of miR-221 in LNCaP reduced the transcription of a subgroup of androgen-responsive genes without affecting the androgen receptor (AR) or AR-androgen integrity. By performing systematic biochemical and bioinformatical analyses, we identified two miR-221 targets, HECTD2 and RAB1A, which could mediate the development of CRPC phenotype in multiple prostate cancer cell lines. Downregulation of HECTD2 significantly affected the androgen-induced and AR-mediated transcription, and downregulation of HECTD2 or RAB1A enhances AI cell growth. As a result of the elevated expression of miR-221, expression of many cell cycle genes was altered and pathways promoting epithelial to mesenchymal transition/tumor metastasis were activated. We hypothesize that a major biological consequence of upregulation of miR-221 is reprogramming of AR signaling, which in turn may mediate the transition to the CRPC phenotype. C1 [Sun, T.; Wang, X.; He, H. H.; Sweeney, C. J.; Brown, M.; Lee, G-S M.; Kantoff, P. W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [He, H. H.; Liu, S. X.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Balk, S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Canc Biol Program,Dept Med, Boston, MA 02215 USA. RP Lee, GSM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Gwo-shu_lee@dfci.harvard.edu; philip_kantoff@dfci.harvard.edu OI Brown, Myles/0000-0002-8213-1658 FU SPORE in Prostate Cancer [2 P50 CA090381-06]; Department of Defense (DoD) Prostate Cancer Training [W81XWH-09-1-0372] FX This work was supported by a SPORE in Prostate Cancer 2 P50 CA090381-06 and TS was supported by a Department of Defense (DoD) Prostate Cancer Training Award W81XWH-09-1-0372. We thank Dr Peter T Nelson at University of Kentucky and Dr Zissimos Mourelatos at University of Pennsylvania for kindly providing us the anti-AGO antibody. We also thank Dr Wang-xia Wang for technical suggestions on AGO-RIP-Chip experiments. NR 50 TC 42 Z9 44 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD MAY 22 PY 2014 VL 33 IS 21 BP 2790 EP 2800 DI 10.1038/onc.2013.230 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA AI9EH UT WOS:000337231700012 PM 23770851 ER PT J AU Birnbaum, ME Mendoza, JL Sethi, DK Dong, S Glanville, J Dobbins, J Ozkan, E Davis, MM Wucherpfennig, KW Garcia, KC AF Birnbaum, Michael E. Mendoza, Juan L. Sethi, Dhruv K. Dong, Shen Glanville, Jacob Dobbins, Jessica Oezkan, Engin Davis, Mark M. Wucherpfennig, Kai W. Garcia, K. Christopher TI Deconstructing the Peptide-MHC Specificity of T Cell Recognition SO CELL LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MYELIN BASIC-PROTEIN; CLASS-II MHC; RECEPTOR CROSS-REACTIVITY; YEAST SURFACE DISPLAY; MULTIPLE-SCLEROSIS; MOLECULAR MIMICRY; DIRECTED EVOLUTION; ANTIGEN; LIGANDS AB In order to survey a universe of major histocompatibility complex (MHC)-presented peptide antigens whose numbers greatly exceed the diversity of the T cell repertoire, T cell receptors (TCRs) are thought to be cross- reactive. However, the nature and extent of TCR cross- reactivity has not been conclusively measured experimentally. We developed a system to identify MHC-presented peptide ligands by combining TCR selection of highly diverse yeast-displayed peptide-MHC libraries with deep sequencing. Although we identified hundreds of peptides reactive with each of five different mouse and human TCRs, the selected peptides possessed TCR recognition motifs that bore a close resemblance to their known antigens. This structural conservation of the TCR interaction surface allowed us to exploit deep-sequencing information to computationally identify activating microbial and self-ligands for human autoimmune TCRs. The mechanistic basis of TCR cross- reactivity described here enables effective surveillance of diverse self and foreign antigens without necessitating degenerate recognition of nonhomologous peptides. C1 [Birnbaum, Michael E.; Mendoza, Juan L.; Dong, Shen; Oezkan, Engin; Garcia, K. Christopher] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. [Birnbaum, Michael E.; Mendoza, Juan L.; Dong, Shen; Oezkan, Engin; Garcia, K. Christopher] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA. [Glanville, Jacob; Davis, Mark M.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. [Birnbaum, Michael E.; Glanville, Jacob; Davis, Mark M.; Garcia, K. Christopher] Stanford Univ, Sch Med, Program Immunol, Stanford, CA 94305 USA. [Oezkan, Engin; Davis, Mark M.; Garcia, K. Christopher] Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. [Sethi, Dhruv K.; Dobbins, Jessica; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Dobbins, Jessica; Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. RP Garcia, KC (reprint author), Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA. EM kcgarcia@stanford.edu OI Birnbaum, Michael/0000-0002-2281-3518; Dobbins, Jessica/0000-0002-6074-5595 FU Regina Casper Stanford Graduate Fellowship; Gerald J. Lieberman Fellowship; National Science Foundation; Helen Hay Whitney Foundation; NIH [PO1 AI045757, R01 AI03867, R01 AI022511, U19 4100041120, P41GM103393]; HHMI; U.S. Department of Energy [DE-AC02-76SF00515]; DOE Office of Biological and Environmental Research; NCI-K01CA175127 FX We thank Suzanne Fischer, Gary Mantalas, and Nelida Prado for technical assistance and Jarrett Adams, Lauren Ely, and Evan Newell for helpful discussions. M.E.B. was supported by a Regina Casper Stanford Graduate Fellowship, a Gerald J. Lieberman Fellowship, and a National Science Foundation Graduate Fellowship. J.L.M. was supported by NCI-K01CA175127 and a Helen Hay Whitney Foundation postdoctoral fellowship. This work was supported by the NIH (PO1 AI045757 to K.W.W., R01 AI03867 to K. C. G., R01 AI022511 to M. M. D., and U19 4100041120 to M. M. D. and K. C. G.) and HHMI (to M. M. D. and K. C. G.). Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and by the National Institutes of Health (including P41GM103393). NR 68 TC 101 Z9 103 U1 7 U2 54 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD MAY 22 PY 2014 VL 157 IS 5 BP 1073 EP 1087 DI 10.1016/j.cell.2014.03.047 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA AH9CG UT WOS:000336437200011 PM 24855945 ER PT J AU Rai, G Joshi, N Jung, JE Liu, Y Schultz, L Yasgar, A Perry, S Diaz, G Zhang, QL Kenyon, V Jadhav, A Simeonov, A Lo, EH van Leyen, K Maloney, DJ Holman, TR AF Rai, Ganesha Joshi, Netra Jung, Joo Eun Liu, Yu Schultz, Lena Yasgar, Adam Perry, Steve Diaz, Giovanni Zhang, Qiangli Kenyon, Victor Jadhav, Ajit Simeonov, Anton Lo, Eng H. van Leyen, Klaus Maloney, David J. Holman, Theodore R. TI Potent and Selective Inhibitors of Human Reticulocyte 12/15-Lipoxygenase as Anti-Stroke Therapies SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PLATELET-TYPE 12-LIPOXYGENASE; SPONGE-DERIVED TERPENOIDS; TRANSIENT FOCAL ISCHEMIA; PANCREATIC-CANCER CELLS; OXIDATIVE STRESS; HUMAN 15-LIPOXYGENASE; 5-LIPOXYGENASE INHIBITION; MAMMALIAN 15-LIPOXYGENASE; GLUTATHIONE DEPLETION; RHEUMATOID-ARTHRITIS AB A key challenge facing drug discovery today is variability of the drug target between species, such as with 12/15-lipoxygenase (12/15-LOX), which contributes to ischemic brain injury, but its human and rodent isozymes have different inhibitor specificities. In the current work, we have utilized a quantitative high-throughput (qHTS) screen to identify compound 1 (ML351), a novel chemotype for 12/15-LOX inhibition that has nanomolar potency (IC50 = 200 nM) against human 12/15-LOX and is protective against oxidative glutamate toxicity in mouse neuronal HT22 cells. In addition, it exhibited greater than 250-fold selectivity versus related LOX isozymes, was a mixed inhibitor, and did not reduce the active-site ferric ion. Lastly, 1 significantly reduced infarct size following permanent focal ischemia in a mouse model of ischemic stroke. As such, this represents the first report of a selective inhibitor of human 12/15-LOX with demonstrated in vivo activity in proof-of-concept mouse models of stroke. C1 [Jung, Joo Eun; Liu, Yu; Lo, Eng H.; van Leyen, Klaus] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Rai, Ganesha; Schultz, Lena; Yasgar, Adam; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Joshi, Netra; Perry, Steve; Diaz, Giovanni; Zhang, Qiangli; Kenyon, Victor; Holman, Theodore R.] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. RP van Leyen, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. EM klaus_vanleyen@hms.harvard.edu; maloneyd@mail.nih.gov; tholman@chemistry.ucsc.edu FU National Institute of Health [R01 GM56062, R01 NS049430, R01 NS069939]; Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research [R03 MH081283, U54MH084681]; National Center for Advancing Translational Sciences; NIH [S10-RR20939]; California Institute for Quantitative Biosciences FX We thank Sam Michael and Richard Jones for automation support; Paul Shinn and Danielle van Leer for assistance with compound management; William Leister, Heather Baker, James Bougie, Elizabeth Fernandez, and Christopher Leclair for analytical chemistry and purification support; Kimloan Nguyen for in vitro ADME data; and Eric Hoobler for helping with the COX assays. Financial support was from the National Institute of Health (grants R01 GM56062 (T.R.H.), R01 NS049430 (K.v.L.), and R01 NS069939) and the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research (R03 MH081283 (T.R.H.)). G.R., L.S., A.Y., A.J., A.S., and D.J.M. were supported by the intramural research program of the National Center for Advancing Translational Sciences and the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research (U54MH084681). Additional financial support was from NIH (S10-RR20939 (T.R.H.)) and the California Institute for Quantitative Biosciences for the UCSC MS Facility (T.R.H.). NR 79 TC 21 Z9 21 U1 4 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD MAY 22 PY 2014 VL 57 IS 10 BP 4035 EP 4048 DI 10.1021/jm401915r PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA AI0BB UT WOS:000336510100010 PM 24684213 ER PT J AU Ramogola-Masire, D Russell, AH Dryden-Peterson, S Efstathiou, JA Kayembe, MKA Wilbur, DC AF Ramogola-Masire, Doreen Russell, Anthony H. Dryden-Peterson, Scott Efstathiou, Jason A. Kayembe, Mukendi K. A. Wilbur, David C. TI Case 16-2014: A 46-Year-Old Woman in Botswana with Postcoital Bleeding SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; SUB-SAHARAN AFRICA; ANTIRETROVIRAL THERAPY; PARTICLE VACCINE; CERVICAL-CANCER; VAGINAL-CANCER; YOUNG-WOMEN; HIV; HPV; PREVENTION C1 [Ramogola-Masire, Doreen] Botswana UPenn Partnership, Philadelphia, PA 19104 USA. [Ramogola-Masire, Doreen] Botswana UPenn Partnership, Gaborone, Botswana. [Ramogola-Masire, Doreen] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Russell, Anthony H.; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Wilbur, David C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dryden-Peterson, Scott] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Russell, Anthony H.; Efstathiou, Jason A.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Dryden-Peterson, Scott] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wilbur, David C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kayembe, Mukendi K. A.] Univ Botswana, Dept Anat Pathol, Natl Hlth Lab, Gaborone, Botswana. [Kayembe, Mukendi K. A.] Univ Botswana, Dept Pathol, Gaborone, Botswana. RP Ramogola-Masire, D (reprint author), Botswana UPenn Partnership, Philadelphia, PA 19104 USA. FU Harvard University Center for AIDS Research [NIH 2P30 AI060354-06]; McCord Hospital (Durban); University of KwaZulu-Natal; South African HIV Clinicians Society; Department of Health, KwaZulu-Natal FX Sponsored by the Harvard University Center for AIDS Research (NIH 2P30 AI060354-06), McCord Hospital (Durban), the University of KwaZulu-Natal, the South African HIV Clinicians Society, and the Department of Health, KwaZulu-Natal. NR 34 TC 1 Z9 1 U1 1 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 22 PY 2014 VL 370 IS 21 BP 2032 EP 2041 DI 10.1056/NEJMcpc1400839 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA AH4UZ UT WOS:000336125500012 PM 24849087 ER PT J AU Turbett, SE Baggett, MV AF Turbett, Sarah E. Baggett, Meridale V. TI Case 5-2014: A Man with Fever, Thrombocytopenia, and Renal Failure REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Turbett, Sarah E.; Baggett, Meridale V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Turbett, SE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 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 MAY 22 PY 2014 VL 370 IS 21 BP 2054 EP 2054 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA AH4UZ UT WOS:000336125500027 PM 24849099 ER PT J AU Lin, L Savoia, E Agboola, F Viswanath, K AF Lin, Leesa Savoia, Elena Agboola, Foluso Viswanath, Kasisomayajula TI What have we learned about communication inequalities during the H1N1 pandemic: a systematic review of the literature SO BMC PUBLIC HEALTH LA English DT Article DE Communication; Communication inequalities; Risk communication H1N1; Pandemic; Public health emergency preparedness ID INFLUENZA-A H1N1; HONG-KONG; VACCINE UPTAKE; UNITED-STATES; BEHAVIORAL-RESPONSES; SEASONAL INFLUENZA; GENERAL-POPULATION; A/H1N1 VACCINATION; MEDIA COVERAGE; HAND HYGIENE AB Background: During public health emergencies, public officials are busy in developing communication strategies to protect the population from existing or potential threats. However, a population's social and individual determinants (i.e. education, income, race/ethnicity) may lead to inequalities in individual or group-specific exposure to public health communication messages, and in the capacity to access, process, and act upon the information received by specific sub-groups-a concept defined as communication inequalities. The aims of this literature review are to: 1) characterize the scientific literature that examined issues related to communication to the public during the H1N1 pandemic, and 2) summarize the knowledge gained in our understanding of social determinants and their association with communication inequalities in the preparedness and response to an influenza pandemic. Methods: Articles were searched in eight major communication, social sciences, and health and medical databases of scientific literature and reviewed by two independent reviewers by following the PRISMA guidelines. The selected articles were classified and analyzed in accordance with the Structural Influence Model of Public Health Emergency Preparedness Communications. Results: A total of 118 empirical studies were included for final review. Among them, 78% were population-based studies and 22% were articles that employed information environment analyses techniques. Consistent results were reported on the association between social determinants of communication inequalities and emergency preparedness outcomes. Trust in public officials and source of information, worry and levels of knowledge about the disease, and routine media exposure as well as information-seeking behaviors, were related to greater likelihood of adoption of recommended infection prevention practices. When addressed in communication interventions, these factors can increase the effectiveness of the response to pandemics. Conclusions: Consistently across studies, a number of potential predictors of behavioral compliance to preventive recommendations during a pandemic were identified. Our findings show the need to include such evidence found in the development of future communication campaigns to ensure the highest rates of compliance with recommended protection measures and reduce communication inequalities during future emergencies. C1 [Lin, Leesa; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Landmark Ctr, Boston, MA 02115 USA. [Lin, Leesa; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Boston, MA 02115 USA. [Savoia, Elena] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lin, Leesa; Savoia, Elena; Agboola, Foluso] Harvard Univ, Sch Publ Hlth, Div Policy Translat & Leadership Dev, Boston, MA 02115 USA. RP Lin, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Landmark Ctr, 677 Huntington Ave,3rd Floor East, Boston, MA 02115 USA. EM llin@hsph.harvard.edu FU U.S. Centers for Disease Control and Prevention (CDC) [5PO1TP000307-05] FX We acknowledge funding support from the U.S. Centers for Disease Control and Prevention (CDC) grant number 5PO1TP000307-05 Supplement. The content of this publication as well as the views and discussions expressed in this paper are solely those of the authors and do not necessarily represent the views of any partner organizations, the CDC or the U.S. Department of Health and Human Services nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. We thank John Mazza for his editing and for critically reviewing the final manuscript. NR 74 TC 4 Z9 5 U1 1 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD MAY 21 PY 2014 VL 14 AR 484 DI 10.1186/1471-2458-14-484 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AI5PS UT WOS:000336922100001 PM 24884634 ER PT J AU Ma, QL Zuo, XH Yang, FS Ubeda, OJ Gant, DJ Alaverdyan, M Kiosea, NC Nazari, S Chen, PP Nothias, F Chan, P Teng, E Frautschy, SA Cole, GM AF Ma, Qiu-Lan Zuo, Xiaohong Yang, Fusheng Ubeda, Oliver J. Gant, Dana J. Alaverdyan, Mher Kiosea, Nicolae C. Nazari, Sean Chen, Ping Ping Nothias, Fatiha Chan, Piu Teng, Edmond Frautschy, Sally A. Cole, Greg M. TI Loss of MAP Function Leads to Hippocampal Synapse Loss and Deficits in the Morris Water Maze with Aging SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; knock-out; MAPs; Morris Water Maze; synaptic markers; tau ID MICROTUBULE-ASSOCIATED PROTEIN; GLYCOGEN-SYNTHASE KINASE-3-BETA; ALPHA-LIPOIC ACID; ALZHEIMERS-DISEASE PATIENTS; MILD COGNITIVE IMPAIRMENT; N-TERMINAL KINASE; MOUSE MODEL; NEUROFIBRILLARY TANGLES; PHOSPHORYLATION SITES; NEURONAL CYTOSKELETON AB Hyperphosphorylation and accumulation of tau aggregates are prominent features in tauopathies, including Alzheimer's disease, but the impact of loss of tau function on synaptic and cognitive deficits remains poorly understood. We report that old (19 - 20 months; OKO) but not middle-aged (8 - 9 months; MKO) tau knock-out mice develop Morris Water Maze(MWM) deficits and loss of hippocampal acetylated alpha-tubulin and excitatory synaptic proteins. Mild motor deficits and reduction in tyrosine hydroxylase (TH) in the substantia nigra were present by middle age, but did not affect MWM performance, whereas OKO mice showed MWM deficits paralleling hippocampal deficits. Deletion of tau, a microtubule-associated protein (MAP), resulted in increased levels of MAP1A, MAP1B, and MAP2 in MKO, followed by loss of MAP2 and MAP1B in OKO. Hippocampal synaptic deficits in OKO mice were partially corrected with dietary supplementation with docosahexaenoic acid (DHA) and both MWM and synaptic deficits were fully corrected by combining DHA with alpha-lipoic acid (ALA), which also prevented TH loss. DHA or DHA/ALA restored phosphorylated and total GSK3 beta and attenuated hyperactivation of the tau C-Jun N-terminal kinases (JNKs) while increasing MAP1B, dephosphorylated (active) MAP2, and acetylated alpha-tubulin, suggesting improved microtubule stability and maintenance of active compensatory MAPs. Our results implicate the loss of MAP function in age-associated hippocampal deficits and identify a safe dietary intervention, rescuing both MAP function and TH in OKO mice. Therefore, in addition to microtubule-stabilizing therapeutic drugs, preserving or restoring compensatory MAP function may be a useful new prevention strategy. C1 [Ma, Qiu-Lan; Zuo, Xiaohong; Yang, Fusheng; Ubeda, Oliver J.; Gant, Dana J.; Alaverdyan, Mher; Kiosea, Nicolae C.; Nazari, Sean; Chen, Ping Ping; Teng, Edmond; Frautschy, Sally A.; Cole, Greg M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Ma, Qiu-Lan; Zuo, Xiaohong; Yang, Fusheng; Ubeda, Oliver J.; Gant, Dana J.; Alaverdyan, Mher; Kiosea, Nicolae C.; Nazari, Sean; Chen, Ping Ping; Teng, Edmond; Frautschy, Sally A.; Cole, Greg M.] Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Nothias, Fatiha] Univ Paris 06, CNRS, INSERM U952, Unite Mixte Rech 7224, F-75005 Paris, France. [Chan, Piu] Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Dept Neurobiol & Neurol, Beijing 10053, Peoples R China. RP Cole, GM (reprint author), Vet Greater Los Angeles Healthcare, Mary S Easton Translat Ctr, 11301 Wilshire Blvd,Bldg 113,Rm 312, Los Angeles, CA 90073 USA. EM frautsch@ucla.edu; gmcole@ucla.edu RI Zuo, Xiaohong/H-6254-2016 FU National Institutes of Health [AT003008]; Alzheimer's Disease Research Center [P01AG16570, RC1AG035878, AG13471, U01 28583, R01AG021975]; Alzheimer's Association [NIRG-07-59659]; UCLA Alzheimer's Disease Research Center Mary S. Easton Drug Discovery Program; UCLA Mary S. Easton Translational Center; Beijing High Standard Health Human Resource Cultural Program [e1e12] FX This work was supported by the National Institutes of Health (Grant AT003008 to G. M. C.; Grant P01AG16570 from the Alzheimer's Disease Research Center to G. M. C.; Grant RC1AG035878 to G. M. C. and S. A. F.; Grant AG13471 to G. M. C.; Grant U01 28583 to S. A. F.; and Grant R01AG021975 to S. A. F.), the Alzheimer's Association (Grant NIRG-07-59659 to Q. L. M.), the UCLA Alzheimer's Disease Research Center Mary S. Easton Drug Discovery Program (G. M. C.), the UCLA Mary S. Easton Translational Center (G. M. C., S. A. F.), and David and Dr. Sharon Comden (S. A. F., G. M. C.). X.Z. was supported by the Beijing High Standard Health Human Resource Cultural Program (Grant e1e12 to P. P. C.). The polyclonal antibody to dephosphorylated, active MAP2 "MAP2 972" was provided by Jesus Avila, PhD (Professor, Universidad Autonoma de Madrid, Spain). NR 80 TC 27 Z9 28 U1 0 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 21 PY 2014 VL 34 IS 21 BP 7124 EP 7136 DI 10.1523/JNEUROSCI.3439-13.2014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA AI5HB UT WOS:000336895200010 PM 24849348 ER PT J AU Liao, F Hori, Y Hudry, E Bauer, AQ Jiang, H Mahan, TE Lefton, KB Zhang, TJ Dearborn, JT Kim, J Culver, JP Betensky, R Wozniak, DF Hyman, BT Holtzman, DM AF Liao, Fan Hori, Yukiko Hudry, Eloise Bauer, Adam Q. Jiang, Hong Mahan, Thomas E. Lefton, Katheryn B. Zhang, Tony J. Dearborn, Joshua T. Kim, Jungsu Culver, Joseph P. Betensky, Rebecca Wozniak, David F. Hyman, Bradley T. Holtzman, David M. TI Anti-ApoE Antibody Given after Plaque Onset Decreases A beta Accumulation and Improves Brain Function in a Mouse Model of A beta Amyloidosis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's; amyloid; antibody; apolipoprotein E ID PROTEIN TRANSGENIC MICE; HUMAN APOLIPOPROTEIN-E; DENSITY-LIPOPROTEIN RECEPTOR; ALZHEIMERS-DISEASE; PASSIVE IMMUNOTHERAPY; TYPE-4 ALLELE; GENE-TRANSFER; IN-VIVO; DEPOSITION; PATHOLOGY AB Apolipoprotein E (apoE) is the strongest known genetic risk factor for late onset Alzheimer's disease (AD). It influences amyloid-beta(A beta) clearance and aggregation, which likely contributes in large part to its role in AD pathogenesis. We recently found that HJ6.3, a monoclonal antibody against apoE, significantly reduced A beta plaque load when given to APPswe/PS1 Delta E9 (APP/PS1) mice starting before the onset of plaque deposition. To determine whether the anti-apoE antibody HJ6.3 affects A beta plaques, neuronal network function, and behavior in APP/PS1 mice after plaque onset, we administered HJ6.3 (10 mg/kg/week) or PBS intraperitoneally to 7-month-old APP/PS1 mice for 21 weeks. HJ6.3 mildly improved spatial learning performance in the water maze, restored resting-state functional connectivity, and modestly reduced brain A beta plaque load. There was no effect of HJ6.3 on total plasma cholesterol or cerebral amyloid angiopathy. To investigate the underlying mechanisms of anti-apoE immunotherapy, HJ6.3 was applied to the brain cortical surface and amyloid deposition was followed over 2 weeks using in vivo imaging. Acute exposure to HJ6.3 affected the course of amyloid deposition in that it prevented the formation of new amyloid deposits, limited their growth, and was associated with occasional clearance of plaques, a process likely associated with direct binding to amyloid aggregates. Topical application of HJ6.3 for only 14 d also decreased the density of amyloid plaques assessed postmortem. Collectively, these studies suggest that anti-apoE antibodies have therapeutic potential when given before or after the onset of A beta pathology. C1 [Liao, Fan; Jiang, Hong; Mahan, Thomas E.; Lefton, Katheryn B.; Zhang, Tony J.; Holtzman, David M.] Washington Univ, Dept Neurol, Sch Med, St Louis, MO 63110 USA. [Liao, Fan; Jiang, Hong; Mahan, Thomas E.; Lefton, Katheryn B.; Zhang, Tony J.; Wozniak, David F.; Holtzman, David M.] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA. [Liao, Fan; Jiang, Hong; Mahan, Thomas E.; Lefton, Katheryn B.; Zhang, Tony J.; Holtzman, David M.] Washington Univ, Sch Med, Charles F & Joanne Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA. [Bauer, Adam Q.; Culver, Joseph P.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Dearborn, Joshua T.; Wozniak, David F.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Hori, Yukiko; Hudry, Eloise; Hyman, Bradley T.] Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Hori, Yukiko; Hudry, Eloise; Hyman, Bradley T.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Wozniak, David F.] Washington Univ, Sch Med, Taylor Family Inst Innovat Psychiat Res, St Louis, MO 63110 USA. [Kim, Jungsu] Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. [Betensky, Rebecca] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Holtzman, DM (reprint author), Washington Univ, Dept Neurol, Sch Med, 660 S Euclid Ave,Box 8111, St Louis, MO 63110 USA. EM holtzman@neuro.wustl.edu OI Mahan, Thomas/0000-0001-9811-7490; Liao, Fan/0000-0003-4874-460X FU BrightFocus Foundation [A2013037F]; AstraZeneca; Cure Alzheimer's Fund; Dreyfoos Program; Uehara Memorial Foundation; National Institutes of Health [R37 AG13956]; Eli Lilly FX This work was supported by the BrightFocus Foundation (Grant A2013037F to F. L.), AstraZeneca (D. M. H.), the Cure Alzheimer's Fund (D. M. H.), the Dreyfoos Program (B. T. H. and E. H.), the Uehara Memorial Foundation (post-doctoral fellowship to Y.H.), and the National Institutes of Health (Grant R37 AG13956 to D.M.H.).; D.M.H. and Washington University have ownership interests in C2N Diagnostics. D. M. H. is on the scientific advisory board of C2N Diagnostics, consults for AstraZeneca, Genentech, and Eli Lilly, and his laboratory receives research grants from AstraZeneca and Eli Lilly. The remaining authors declare no competing financial interests. NR 54 TC 19 Z9 20 U1 0 U2 17 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 21 PY 2014 VL 34 IS 21 BP 7281 EP 7292 DI 10.1523/JNEUROSCI.0646-14.2014 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AI5HB UT WOS:000336895200022 PM 24849360 ER PT J AU Harrison, WJ Bex, PJ AF Harrison, William J. Bex, Peter J. TI Integrating Retinotopic Features in Spatiotopic Coordinates SO JOURNAL OF NEUROSCIENCE LA English DT Article DE crowding; feature integration; remapping; spatiotopy; trans-saccade; visual stability ID SACCADIC EYE-MOVEMENTS; HUMAN OCCIPITAL CORTEX; OBJECT RECOGNITION; VISUAL-MOTION; PSYCHOPHYSICS TOOLBOX; RECEPTIVE-FIELDS; PARIETAL CORTEX; REFERENCE FRAME; ATTENTION; SPACE AB The receptive fields of early visual neurons are anchored in retinotopic coordinates (Hubel and Wiesel, 1962). Eye movements shift these receptive fields and therefore require that different populations of neurons encode an object's constituent features across saccades. Whether feature groupings are preserved across successive fixations or processing starts anew with each fixation has been hotly debated (Melcher and Morrone, 2003; Melcher, 2005, 2010; Knapen et al., 2009; Cavanagh et al., 2010a, b; Morris et al., 2010). Here we show that feature integration initially occurs within retinotopic coordinates, but is then conserved within a spatiotopic coordinate frame independent of where the features fall on the retinas. With human observers, we first found that the relative timing of visual features plays a critical role in determining the spatial area over which features are grouped. We exploited this temporal dependence of feature integration to show that features co-occurring within 45 ms remain grouped across eye movements. Our results thus challenge purely feedforward models of feature integration (Pelli, 2008; Freeman and Simoncelli, 2011) that begin de novo after every eye movement, and implicate the involvement of brain areas beyond early visual cortex. The strong temporal dependence we quantify and its link with trans-saccadic object perception instead suggest that feature integration depends, at least in part, on feedback from higher brain areas (Mumford, 1992; Rao and Ballard, 1999; Di Lollo et al., 2000; Moore and Armstrong, 2003; Stanford et al., 2010). C1 [Harrison, William J.; Bex, Peter J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. RP Harrison, WJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA 02114 USA. EM willjharri@gmail.com OI Harrison, William/0000-0002-6408-0359 FU National Institutes of Health [R01 EY19281, R01 EY018664] FX This work was supported by National Institutes of Health Grants R01 EY19281 and R01 EY018664. We thank MiYoung Kwon for her help with preparing the manuscript. NR 70 TC 9 Z9 9 U1 0 U2 18 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 21 PY 2014 VL 34 IS 21 BP 7351 EP 7360 DI 10.1523/JNEUROSCI.5252-13.2014 PG 10 WC Neurosciences SC Neurosciences & Neurology GA AI5HB UT WOS:000336895200029 PM 24849367 ER PT J AU Shapiro, IM Kolev, VN Vidal, CM Kadariya, Y Ring, JE Wright, Q Weaver, DT Menges, C Padval, M McClatchey, AI Xu, QL Testa, JR Pachter, JA AF Shapiro, Irina M. Kolev, Vihren N. Vidal, Christian M. Kadariya, Yuwaraj Ring, Jennifer E. Wright, Quentin Weaver, David T. Menges, Craig Padval, Mahesh McClatchey, Andrea I. Xu, Qunli Testa, Joseph R. Pachter, Jonathan A. TI Merlin Deficiency Predicts FAK Inhibitor Sensitivity: A Synthetic Lethal Relationship SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID FOCAL-ADHESION KINASE; MALIGNANT MESOTHELIOMA CELLS; TUMOR-SUPPRESSOR; ADHERENS JUNCTIONS; BREAST-CANCER; STEM-CELLS; NF2; GENE; TUMORIGENESIS; MUTATIONS AB The goal of targeted therapy is to match a selective drug with a genetic lesion that predicts for drug sensitivity. In a diverse panel of cancer cell lines, we found that the cells most sensitive to focal adhesion kinase (FAK) inhibition lack expression of the neurofibromatosis type 2 (NF2) tumor suppressor gene product, Merlin. Merlin expression is often lost in malignant pleural mesothelioma (MPM), an asbestos-induced aggressive cancer with limited treatment options. Our data demonstrate that low Merlin expression predicts for increased sensitivity of MPM cells to a FAK inhibitor, VS-4718, in vitro and in tumor xenograft models. Disruption of MPM cell-cell or cell-extracellular matrix (ECM) contacts with blocking antibodies suggests that weak cell-cell adhesions in Merlinnegative MPM cells underlie their greater dependence on cell-ECM-induced FAK signaling. This provides one explanation of why Merlin-negative cells are vulnerable to FAK inhibitor treatment. Furthermore, we validated aldehyde dehydrogenase as a marker of cancer stem cells (CSCs) in MPM, a cell population thought to mediate tumor relapse after chemotherapy. Whereas pemetrexed and cisplatin, standard-of-care agents for MPM, enrich for CSCs, FAK inhibitor treatment preferentially eliminates these cells. These preclinical results provide the rationale for a clinical trial in MPM patients using a FAK inhibitor as a single agent after first-line chemotherapy. With this design, the FAK inhibitor could potentially induce a more durable clinical response through reduction of CSCs along with a strong antitumor effect. Furthermore, our data suggest that patients with Merlin-negative tumors may especially benefit from FAK inhibitor treatment. C1 [Shapiro, Irina M.; Kolev, Vihren N.; Vidal, Christian M.; Ring, Jennifer E.; Wright, Quentin; Weaver, David T.; Padval, Mahesh; Xu, Qunli; Pachter, Jonathan A.] Verastem Inc, Cambridge, MA 02142 USA. [Kadariya, Yuwaraj; Menges, Craig; Testa, Joseph R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [McClatchey, Andrea I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [McClatchey, Andrea I.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP Pachter, JA (reprint author), Verastem Inc, Cambridge, MA 02142 USA. EM jpachter@verastem.com FU Verastem Inc; NIH [R01CA113733]; MGH Research Scholars Award; National Cancer Institute [CA148805] FX This work was funded by Verastem Inc. A.I.M. was also funded by the NIH (R01CA113733) and an MGH Research Scholars Award. J.R.T., C.M.V., and Y.K. were also supported by National Cancer Institute grant CA148805. NR 34 TC 33 Z9 33 U1 0 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAY 21 PY 2014 VL 6 IS 237 AR 237ra68 DI 10.1126/scitranslmed.3008639 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA AI2DY UT WOS:000336668800009 PM 24848258 ER EF