FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Musset, B Clark, RA DeCoursey, TE Petheo, GL Geiszt, M Chen, YM Cornell, JE Eddy, CA Brzyski, RG El Jamali, A AF Musset, Boris Clark, Robert A. DeCoursey, Thomas E. Petheo, Gabor L. Geiszt, Miklos Chen, Yumin Cornell, John E. Eddy, Carlton A. Brzyski, Robert G. El Jamali, Amina TI NOX5 in Human Spermatozoa EXPRESSION, FUNCTION, AND REGULATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NADPH OXIDASE NOX5-S; ESOPHAGEAL ADENOCARCINOMA CELLS; OXYGEN SPECIES PRODUCTION; HUMAN SPERM SUSPENSIONS; GATED PROTON CHANNEL; HUMAN EOSINOPHILS; SUPEROXIDE-PRODUCTION; RESPIRATORY BURST; ELECTRON CURRENTS; HUMAN NEUTROPHILS AB Physiological and pathological processes in spermatozoa involve the production of reactive oxygen species (ROS), but the identity of the ROS-producing enzyme system(s) remains a matter of speculation. We provide the first evidence that NOX5 NADPH oxidase is expressed and functions in human spermatozoa. Immunofluorescence microscopy detected NOX5 protein in both the flagella/neck region and the acrosome. Functionally, spermatozoa exposed to calcium ionophore, phorbol ester, or H2O2 exhibited superoxide anion production, which was blocked by addition of superoxide dismutase, a Ca2+ chelator, or inhibitors of either flavoprotein oxidases (diphenylene iododonium) or NOX enzymes (GKT136901). Consistent with our previous overexpression studies, we found that H2O2-induced superoxide production by primary sperm cells was mediated by the non-receptor tyrosine kinase c-Abl. Moreover, the H(V)1 proton channel, which was recently implicated in spermatozoa motility, was required for optimal superoxide production by spermatozoa. Immunoprecipitation experiments suggested an interaction among NOX5, c-Abl, and H(V)1. H2O2 treatment increased the proportion of motile sperm in a NOX5-dependent manner. Statistical analyses showed a pH-dependent correlation between superoxide production and enhanced sperm motility. Collectively, our findings show that NOX5 is a major source of ROS in human spermatozoa and indicate a role for NOX5-dependent ROS generation in human spermatozoa motility. C1 [Clark, Robert A.; El Jamali, Amina] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Chen, Yumin; Cornell, John E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Eddy, Carlton A.; Brzyski, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Musset, Boris; DeCoursey, Thomas E.] Rush Univ, Med Ctr, Dept Physiol & Mol Biophys, Chicago, IL 60612 USA. [Petheo, Gabor L.; Geiszt, Miklos] Semmelweis Univ, Fac Med, Dept Physiol, H-1085 Budapest, Hungary. RP El Jamali, A (reprint author), 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM AkoulouzeBik@uthscsa.edu RI Musset, Boris/J-2520-2013; OI Musset, Boris/0000-0001-8242-8817; DeCoursey, Thomas/0000-0002-4263-180X FU National Institutes of Health [T32 HL04776, UL1 RR025767, KL2 RR025766, K01 DK084297, R01-GM087507, P30 CA054174, P30 AG013319, P01 AG019316]; Iacocca Family Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grants T32 HL04776 (to A. E. J.), UL1 RR025767 (to A. E. J.), Clinical and Translational Science Awards pilot funding (to A. E. J.), KL2 RR025766 (to A. E. J.), K01 DK084297 (to A. E. J.), and Career Development Award R01-GM087507 (to T. E. D.) and an award from the Iacocca Family Foundation (to B. M.). Robert Clark is a scientific co-founder, member of the Scientific Advisory Board, and equity holder in GenKyoTex SA, a Swiss biotechnology start-up company with a primary goal of developing clinically useful inhibitors of the NOX family of NADPH oxidases.; Optical Imaging Facility of the University of Texas Health Science Center at San Antonio, which is supported by National Institutes of Health Grants P30 CA054174 (Cancer Therapy and Research Center), P30 AG013319 (Nathan Shock Center), and P01 AG019316 (Aging, Oxidative Stress and Cell Death). We thank Dr. Craig Witz for arranging initial access to human sperm samples from the University of Texas Medicine Fertility Center, Drs. Victoria Frohlich and Shivani Maffi for expert guidance on confocal microscopy image acquisition and analysis, Maria Gamez and Mario de la Pena for expert technical assistance, and Drs. Susan Smith, Yves Gorin, and Denis Feliers for helpful discussions. NR 72 TC 44 Z9 45 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 16 PY 2012 VL 287 IS 12 BP 9376 EP 9388 DI 10.1074/jbc.M111.314955 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912KV UT WOS:000301797800068 PM 22291013 ER PT J AU Cherry, ABC Daley, GQ AF Cherry, Anne B. C. Daley, George Q. TI Reprogramming Cellular Identity for Regenerative Medicine SO CELL LA English DT Review ID PLURIPOTENT STEM-CELLS; HUMAN SOMATIC-CELLS; IPS CELLS; DEFINED FACTORS; PARKINSONS-DISEASE; MOTOR-NEURONS; HEMATOPOIETIC DIFFERENTIATION; GENETIC CORRECTION; DNA METHYLATION; IN-VIVO AB Although development leads unidirectionally toward more restricted cell fates, recent work in cellular reprogramming has proven that one cellular identity can strikingly convert into another, promising countless applications in biomedical research and paving the way for modeling diseases with patient-derived stem cells. To date, there has been little discussion of which disease models are likely to be most informative. Here, we review evidence demonstrating that, because environmental influences and epigenetic signatures are largely erased during reprogramming, patient-specific models of diseases with strong genetic bases and high penetrance are likely to prove most informative in the near term. We also discuss the implications of the new reprogramming paradigm in biomedicine and outline how reprogramming of cell identities is enhancing our understanding of cell differentiation and prospects for cellular therapies and in vivo regeneration. C1 [Cherry, Anne B. C.; Daley, George Q.] Childrens Hosp Boston, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA. [Cherry, Anne B. C.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cherry, Anne B. C.; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Cherry, Anne B. C.; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Cherry, Anne B. C.; Daley, George Q.] Broad Inst, Cambridge, MA 02142 USA. [Cherry, Anne B. C.; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Daley, GQ (reprint author), Childrens Hosp Boston, Howard Hughes Med Inst, Manton Ctr Orphan Dis Res, Div Pediat Hematol Oncol,Stem Cell Transplantat P, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu RI perumal, murugiah/D-1565-2012; Cherry, Anne/E-7333-2011 FU NIH [RO1-DK70055, UO1-HL100001, RC4-DK090913, P50HG005550]; ARRA [RC2-HL102815]; Roche Foundation for Anemia Research; Alex's Lemonade Stand; Ellison Medical Foundation; Doris Duke Medical Foundation; Harvard Stem Cell Institute FX G.Q.D. is supported by grants from the NIH (RO1-DK70055, UO1-HL100001, RC4-DK090913, P50HG005550, and special funds from the ARRA stimulus package RC2-HL102815), the Roche Foundation for Anemia Research, Alex's Lemonade Stand, Ellison Medical Foundation, Doris Duke Medical Foundation, and the Harvard Stem Cell Institute. G.Q.D. is an affiliate member of the Broad Institute and the Leukemia and Lymphoma Society, and an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. NR 99 TC 78 Z9 79 U1 8 U2 59 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 16 PY 2012 VL 148 IS 6 BP 1110 EP 1122 DI 10.1016/j.cell.2012.02.031 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 913PI UT WOS:000301889500010 PM 22424223 ER PT J AU Kathiresan, S Srivastava, D AF Kathiresan, Sekar Srivastava, Deepak TI Genetics of Human Cardiovascular Disease SO CELL LA English DT Review ID CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; EPITHELIAL SODIUM-CHANNEL; C-REACTIVE PROTEIN; LONG-QT SYNDROME; PLURIPOTENT STEM-CELLS; HOLT-ORAM-SYNDROME; HEART-DISEASE; MYOCARDIAL-INFARCTION AB Cardiovascular disease encompasses a range of conditions extending from myocardial infarction to congenital heart disease, most of which are heritable. Enormous effort has been invested in understanding the genes and specific DNA sequence variants that are responsible for this heritability. Here, we review the lessons learned for monogenic and common, complex forms of cardiovascular disease. We also discuss key challenges that remain for gene discovery and for moving from genomic localization to mechanistic insights, with an emphasis on the impact of next-generation sequencing and the use of pluripotent human cells to understand the mechanism by which genetic variation contributes to disease. C1 [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Kathiresan, Sekar] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Srivastava, Deepak] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA. [Srivastava, Deepak] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94158 USA. [Srivastava, Deepak] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM skathiresan@partners.org; dsrivastava@gladstone.ucsf.edu RI perumal, murugiah/D-1565-2012 FU NHLBI/NIH; Foundation Leducq; Massachusetts General Hospital; Pfizer; Merck; Alnylam; Shire Therapeutics; California Institute for Regenerative Medicine; Younger Family Foundation; Roddenberry Foundation; Whittier Foundation FX The authors wish to apologize in advance to authors of outstanding work that is not acknowledged in this Review due to space constraints. The authors wish to thank Drs. Ron Do, Nathan O. Stitziel, Gina M. Peloso, and Kiran Musunuru for assistance with analyses and critical review of the manuscript. S.K. was supported by grants from NHLBI/NIH, Foundation Leducq, the Howard Goodman Fellowship from Massachusetts General Hospital, Pfizer, Merck, Alnylam, and Shire Therapeutics. D.S. was supported by grants from the NHLBI/NIH, the California Institute for Regenerative Medicine, the Younger Family Foundation, the Roddenberry Foundation, and the Whittier Foundation. NR 132 TC 113 Z9 117 U1 6 U2 61 PU CELL PRESS PI CAMBRIDGE PA 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD MAR 16 PY 2012 VL 148 IS 6 BP 1242 EP 1257 DI 10.1016/j.cell.2012.03.001 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 913PI UT WOS:000301889500019 PM 22424232 ER PT J AU Hajjarian, Z Nadkarni, SK AF Hajjarian, Zeinab Nadkarni, Seemantini K. TI Evaluating the Viscoelastic Properties of Tissue from Laser Speckle Fluctuations SO SCIENTIFIC REPORTS LA English DT Article ID DIFFUSING-WAVE-SPECTROSCOPY; DYNAMIC LIGHT-SCATTERING; ATHEROSCLEROTIC PLAQUES; COMPLEX FLUIDS; CANCER; MICRORHEOLOGY; BIOMECHANICS; RUPTURE; DISEASE; STRESS AB Most pathological conditions such as atherosclerosis, cancer, neurodegenerative, and orthopedic disorders are accompanied with alterations in tissue viscoelasticity. Laser Speckle Rheology (LSR) is a novel optical technology that provides the invaluable potential for mechanical assessment of tissue in situ. In LSR, the specimen is illuminated with coherent light and the time constant of speckle fluctuations, tau, is measured using a high speed camera. Prior work indicates that tau is closely correlated with tissue microstructure and composition. Here, we investigate the relationship between LSR measurements of tau and sample mechanical properties defined by the viscoelastic modulus, G(star). Phantoms and tissue samples over a broad range of viscoelastic properties are evaluated using LSR and conventional mechanical testing. Results demonstrate a strong correlation between tau and vertical bar G(star)vertical bar for both phantom (r = 0.79, p < 0.0001) and tissue (r = 0.88, p<0.0001) specimens, establishing the unique capability of LSR in characterizing tissue viscoelasticity. C1 [Hajjarian, Zeinab; Nadkarni, Seemantini K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. RP Nadkarni, SK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. EM snadkarni@partners.org FU NIH [R21 HL 088306]; ARRA [R21 HL 088306-02S1] FX This work was supported in part by the NIH grant No. R21 HL 088306 (S.N) and the ARRA grant No. R21 HL 088306-02S1 (S.N.). NR 40 TC 15 Z9 15 U1 0 U2 22 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 MAR 16 PY 2012 VL 2 AR 316 DI 10.1038/srep00316 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 912DI UT WOS:000301774500001 PM 22428085 ER PT J AU Mijailovich, SM Li, XC Griffiths, RH Geeves, MA AF Mijailovich, Srboljub M. Li, Xiaochuan Griffiths, R. Hugh Geeves, Michael A. TI The Hill Model for Binding Myosin S1 to Regulated Actin Is not Equivalent to the McKillop-Geeves Model SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Ca2+ sensitivity; tropomyosin-troponin-actin; stop flow; titrations; cooperativity ID TROPONIN-TROPOMYOSIN COMPLEX; MUSCLE THIN-FILAMENTS; COOPERATIVE BINDING; SUBFRAGMENT-1; SENSITIVITY; MICROSCOPY; COMPONENTS; ISOFORMS AB The Hill two-state cooperativity model and the McKillop-Geeves (McK-G) three-state model predict very similar binding traces of myosin subfragment 1 (S1) binding to regulated actin filaments in the presence and absence of calcium, and both fit the experimental data reasonably well [Chen et al., Biophys. J., 80, 2338-2349]. Here, we compared the Hill model and the McK-G model for binding myosin S1 to regulated actin against three sets of experimental data: the titration of regulated actin with S1 and the kinetics of S1 binding of regulated actin with either excess S1 to actin or excess actin to S1. Each data set was collected for a wide range of specified calcium concentrations. Both models were able to generate reasonable fits to the time course data and to titration data. The McK-G model can fit all three data sets with the same calcium-concentration-sensitive parameters. Only K-B and K-T show significant calcium dependence, and the parameters have a classic pCa curve. A unique set of the Hill model parameters was extremely difficult to estimate from the best fits of multiple sets of data. In summary, the McK-G cooperativity model more uniquely resolves parameters estimated from kinetic and titration data than the Hill model, predicts a sigmoidal dependence of key parameters with calcium concentration, and is simpler and more suitable for practical use. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Mijailovich, Srboljub M.; Li, Xiaochuan] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Griffiths, R. Hugh; Geeves, Michael A.] Univ Kent, Dept Biosci, Canterbury CT2 7NJ, Kent, England. [Mijailovich, Srboljub M.] Tufts Med Sch, CBR, Dept Med, Steward St Elizabeth Med Ctr, Boston, MA 02135 USA. RP Mijailovich, SM (reprint author), Tufts Med Sch, CBR, Dept Med, Steward St Elizabeth Med Ctr, Room 406,736 Cambridge St, Boston, MA 02135 USA. EM smijailo@hsph.harvard.edu; m.a.geeves@kent.ac.uk RI Geeves, Michael/F-7583-2011; OI Mijailovich, Srboljub/0000-0003-1498-308X FU National Institutes of Health [R01 AR048776]; Wellcome Trust [085309] FX This work was supported by National Institutes of Health grant no. R01 AR048776 to S.M. and Wellcome Trust Program grant no. 085309 to M.G. We gratefully acknowledge Dr. Thomas Irving for critical reading of this article. NR 24 TC 5 Z9 5 U1 0 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 16 PY 2012 VL 417 IS 1-2 BP 112 EP 128 DI 10.1016/j.jmb.2012.01.011 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 910XW UT WOS:000301682900009 PM 22306466 ER PT J AU Hohmann, EL Kim, J AF Hohmann, Elizabeth L. Kim, JiYeon TI Case 8-2012: A 53-Year-Old Man with Crohn's Disease, Diarrhea, Fever, and Bacteremia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LISTERIA-MONOCYTOGENES; GASTROENTERITIS C1 [Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kim, JiYeon] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hohmann, Elizabeth L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kim, JiYeon] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hohmann, EL (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 7 TC 5 Z9 5 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 15 PY 2012 VL 366 IS 11 BP 1039 EP 1045 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 908HZ UT WOS:000301482800009 PM 22417258 ER PT J AU Thomas, T Karr, S Kelley, KW McBane, S AF Thomas, Tyan Karr, Samantha Kelley, Kristi W. McBane, Sarah TI Overcoming barriers to scholarly activity in a clinical practice setting SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID PHARMACY PRACTICE FACULTY C1 [Thomas, Tyan] Univ Sci Philadelphia, Philadelphia Coll Pharm, Philadelphia, PA 19104 USA. [Thomas, Tyan] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Karr, Samantha] Glendale Midwestern Univ, Coll Pharm, Glendale, AZ USA. [Kelley, Kristi W.] Auburn Univ, Harrison Sch Pharm, Auburn, AL 36849 USA. [Kelley, Kristi W.] Baptist Hlth Syst Inc, Trinity Med Ctr, Continu Clin, Birmingham, AL USA. [McBane, Sarah] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. RP Thomas, T (reprint author), Univ Sci Philadelphia, Philadelphia Coll Pharm, 600 S 43rd St, Philadelphia, PA 19104 USA. EM t.thomas@usp.edu NR 7 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAR 15 PY 2012 VL 69 IS 6 BP 465 EP 467 DI 10.2146/ajhp110290 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 943LO UT WOS:000304123700005 PM 22382476 ER PT J AU Poon, LH Lee, AJ Chiao, TB Kang, GA Heath, S Glass, GA AF Poon, Linda H. Lee, Audrey J. Chiao, Teresa B. Kang, Gail A. Heath, Susan Glass, Graham A. TI Pharmacist's role in a Parkinson's disease and movement disorders clinic SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE Ambulatory care; Clinical pharmacists; Clinical pharmacy; Department of Veterans Affairs; Movement disorders; Parkinson disease; Patient information; Pharmaceutical services; Team ID MANAGEMENT AB Purpose. The expanding role of a clinical pharmacist at a Veterans Affairs (VA) outpatient clinic for patients with Parkinson's disease (PD) and movement disorders is described. Summary. San Francisco VA Medical Center added a clinical pharmacist to the multidisciplinary team serving patients at an outpatient clinic operated by its Parkinson's Disease Research, Education and Clinical Center (PADRECC). During the first six months after joining the clinic team, the pharmacist met with 131 patients and made a total of 69 drug therapy recommendations that were implemented by neurologists, clinical nurse specialists, and other PADRECC providers. The results of a retrospective chart review suggested that in about 21% of the cases evaluated, the pharmacist's recommendations contributed to an improved medical outcome or the resolution of a medical problem. Anonymous surveys indicated that clinic providers (n = 33) and patients (n = 20) were satisfied with the pharmacist's services. Using a five-point Likert scale (scores ranged from 1 for "strongly disagree" to 5 for "strongly agree") that they had more time to devote to other clinic responsibilities with the pharmacist present in the clinic (mean score, 4.79); patients indicated that they had an improved understanding of their medications after speaking with the pharmacist (mean score, 4.88). Conclusion. A clinical pharmacist's regular involvement in an outpatient PD and movement disorders clinic has been well received by patients and clinic providers. The study results suggest that the pharmacist has made important contributions in areas such as therapeutic problem solving and medication education while freeing up providers for other responsibilities. C1 [Poon, Linda H.] San Francisco Vet Affairs Med Ctr VAMC, San Francisco, CA USA. [Poon, Linda H.; Chiao, Teresa B.] Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. [Poon, Linda H.; Lee, Audrey J.] Univ Pacific, Thomas J Long Sch Pharm & Hlth Sci, Stockton, CA 95211 USA. [Kang, Gail A.] Univ Calif San Francisco, Neurol Memory & Aging Ctr, San Francisco, CA 94143 USA. [Kang, Gail A.] San Francisco VA Med Ctr, Educ & Clin Ctr PADRECC, San Francisco, CA USA. [Heath, Susan; Glass, Graham A.] San Francisco VA Med Ctr, PADRECC, San Francisco, CA USA. [Glass, Graham A.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. RP Poon, LH (reprint author), San Francisco Vet Affairs Med Ctr 119, 4150 Clement St, San Francisco, CA 94121 USA. EM linda.poon@va.gov NR 10 TC 2 Z9 3 U1 1 U2 3 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAR 15 PY 2012 VL 69 IS 6 BP 518 EP 520 DI 10.2146/ajhp110127 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 943LO UT WOS:000304123700013 PM 22382484 ER PT J AU Yang, XWH Mirchev, R Deng, XY Yacono, P Yang, HL Golan, DE Hemler, ME AF Yang, Xiuwei H. Mirchev, Rossen Deng, Xinyu Yacono, Patrick Yang, Helen L. Golan, David E. Hemler, Martin E. TI CD151 restricts the alpha 6 integrin diffusion mode SO JOURNAL OF CELL SCIENCE LA English DT Article DE Integrin; Tetraspanin; CD151; Single particle tracking; Laminin ID TETRASPANIN-ENRICHED MICRODOMAINS; CELL-MIGRATION; BREAST-CANCER; IN-VIVO; BRANCHING MORPHOGENESIS; ALPHA-3-BETA-1 INTEGRIN; CONFORMATIONAL-CHANGES; CLINICAL-SIGNIFICANCE; ACTIN CYTOSKELETON; BETA(1) INTEGRINS AB Laminin-binding integrins (alpha 3 beta 1, alpha 6 beta 1, alpha 6 beta 4, alpha 7 beta 1) are almost always expressed together with tetraspanin CD151. In every coexpressing cell analyzed to date, CD151 makes a fundamental contribution to integrin-dependent motility, invasion, morphology, adhesion and/or signaling. However, there has been minimal mechanistic insight into how CD151 affects integrin functions. In MDA-MB-231 mammary cells, tetraspanin CD151 knockdown impairs alpha 6 integrin clustering and functions without decreasing alpha 6 integrin expression or activation. Furthermore, CD151 knockdown minimally affects the magnitude of a6 integrin diffusion, as measured using single particle tracking. Instead, CD151 knockdown has a novel and unexpected dysregulating effect on the mode of alpha 6 integrin diffusion. In control cells alpha 6 integrin shows mostly random-confined diffusion (RCD) and some directed motion (DMO). In sharp contrast, in CD151-knockdown cells alpha 6 integrin shows mostly DMO. In control cells alpha 6 diffusion mode is sensitive to actin disruption, talin knockdown and phorbol ester stimulation. By contrast, CD151 knockdown cell alpha 6 integrin is sensitive to actin disruption but desensitized to talin knockdown or phorbol ester stimulation, indicating dysregulation. Both phorbol ester and EGF stimulate cell spreading and promote alpha 6 RCD in control cells. By contrast, CD151-ablated cells retain EGF effects but lose phorbol-ester-stimulated spreading and alpha 6 RCD. For alpha 6 integrins, physical association with CD151 promotes alpha 6 RCD, in support of alpha 6-mediated cable formation and adhesion. By comparison, for integrins not associated with CD151 (e.g. av integrins), CD151 affects neither diffusion mode nor alpha v function. Hence, CD151 support of alpha 6 RCD is specific and functionally relevant, and probably underlies diverse CD151 functions in skin, kidney and cancer cells. C1 [Deng, Xinyu; Yang, Helen L.] Univ Kentucky, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA. [Mirchev, Rossen; Yacono, Patrick; Golan, David E.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Sch Med, Boston, MA 02115 USA. [Yang, Xiuwei H.; Hemler, Martin E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Golan, David E.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM xya222@uky.edu; martin_hemler@dfci.harvard.edu RI Deng, Xinyu/J-5732-2015 FU National Institutes of Health [CA42368, HL32854]; S.G. Komen Career Catalyst Award [KG081481]; DOD [W81XWH-07-1-0568] FX This work was supported by National Institutes of Health [grant numbers CA42368 to M.E.H. and HL32854 to D.E.G.]; and by a S.G. Komen Career Catalyst Award [grant number KG081481 to X.H.Y.] and a DOD Concept Award [grant number W81XWH-07-1-0568 to X.H.Y.]. Deposited in PMC for release after 12 months. NR 79 TC 24 Z9 24 U1 2 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR 15 PY 2012 VL 125 IS 6 BP 1478 EP 1487 DI 10.1242/jcs.093963 PG 10 WC Cell Biology SC Cell Biology GA 930QY UT WOS:000303155400012 PM 22328509 ER PT J AU Tokhtaeva, E Sachs, G Sun, HY Dada, LA Sznajder, JI Vagin, O AF Tokhtaeva, Elmira Sachs, George Sun, Haiying Dada, Laura A. Sznajder, Jacob I. Vagin, Olga TI Identification of the amino acid region involved in the intercellular interaction between the beta(1) subunits of Na+/K+-ATPase SO JOURNAL OF CELL SCIENCE LA English DT Article DE Na+/K+-ATPase beta(1) subunit; Epithelial junction; Trans-dimerization ID NECTIN-LIKE MOLECULES; CELL-CELL-ADHESION; EPITHELIAL-CELLS; E-CADHERIN; NA,K-ATPASE; JUNCTIONS; ANKYRIN; ROLES; GLYCOSYLATION; MIGRATION AB Epithelial junctions depend on intercellular interactions between beta(1) subunits of the Na+/K+-ATPase molecules of neighboring cells. The interaction between dog and rat subunits is less effective than the interaction between two dog b1 subunits, indicating the importance of species-specific regions for beta(1)-beta(1) binding. To identify these regions, the species-specific amino acid residues were mapped on a high-resolution structure of the Na+/K+-ATPase beta(1) subunit to select those exposed towards the beta(1) subunit of the neighboring cell. These exposed residues were mutated in both dog and rat YFP-linked beta(1) subunits (YFP-beta(1)) and also in the secreted extracellular domain of the dog beta(1) subunit. Five rat-like mutations in the amino acid region spanning residues 198-207 of the dog YFP-beta(1) expressed in Madin Darby canine kidney (MDCK) cells decreased co-precipitation of the endogenous dog beta(1) subunit with YFP-beta(1) to the level observed between dog beta(1) and rat YFP-beta(1). In parallel, these mutations impaired the recognition of YFP-beta(1) by the dog-specific antibody that inhibits cell adhesion between MDCK cells. Accordingly, dog-like mutations in rat YFP-beta(1) increased both the (YFP-beta(1))-beta(1) interaction in MDCK cells and recognition by the antibody. Conversely, rat-like mutations in the secreted extracellular domain of the dog beta(1) subunit increased its interaction with rat YFP-beta(1) in vitro. In addition, these mutations resulted in a reduction of intercellular adhesion between rat lung epithelial cells following addition of the secreted extracellular domain of the dog beta(1) subunit to a cell suspension. Therefore, the amino acid region 198-207 is crucial for both trans-dimerization of the Na+/K+-ATPase beta(1) subunits and cell-cell adhesion. C1 [Tokhtaeva, Elmira; Sachs, George; Vagin, Olga] Univ Calif Los Angeles, Dept Physiol, Sch Med, Los Angeles, CA 90073 USA. [Tokhtaeva, Elmira; Sachs, George; Vagin, Olga] Vet Adm Greater Los Angeles Hlth Care Syst, VAGLAHS W LA, Los Angeles, CA 90073 USA. [Sun, Haiying; Dada, Laura A.; Sznajder, Jacob I.] Northwestern Univ, Div Pulm & Crit Care Med, Feinberg Sch Med, Chicago, IL 60611 USA. RP Vagin, O (reprint author), Univ Calif Los Angeles, Dept Physiol, Sch Med, Bldg 113,Room 324,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM olgav@ucla.edu FU National Institutes of Health [DK077149, DK058333, R37-HL48129] FX The work was supported by the National Institutes of Health [grant numbers DK077149 to O.V., DK058333 to G.S. and R37-HL48129 to J.I.S.]. Deposited in PMC for release after 12 months. NR 29 TC 9 Z9 11 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR 15 PY 2012 VL 125 IS 6 BP 1605 EP 1616 DI 10.1242/jcs.100149 PG 12 WC Cell Biology SC Cell Biology GA 930QY UT WOS:000303155400023 PM 22328500 ER PT J AU Grossi, PA Costa, AN Fehily, D Blumberg, EA Kuehnert, MJ Fishman, JA Ison, MG Lattes, R Kotton, CN Lilleri, D Kabanova, A Lanzavecchia, A Gerna, G Razonable, RR Comoli, P Zecca, M Basso, S Ginevri, F Grossi, A Schena, FP Rimola, A Burra, P De Martin, E Rodriguez-Castro, KI Fagiuoli, S Pasulo, L Bruno, R Andreone, P Loggi, E Arena, F Rossolini, GM Sganga, G Cozza, V AF Grossi, Paolo A. Costa, Alessandro Nanni Fehily, Deirdre Blumberg, Emily A. Kuehnert, Matthew J. Fishman, Jay A. Ison, Michael G. Lattes, Roberta Kotton, Camille N. Lilleri, Daniele Kabanova, Anne Lanzavecchia, Antonio Gerna, Giuseppi Razonable, Raymund R. Comoli, Patrizia Zecca, Marco Basso, Sabrina Ginevri, Fabrizio Grossi, Alessandra Schena, Francesco P. Rimola, Antoni Burra, Patrizia De Martin, Elenora Rodriguez-Castro, Kryssia Isabel Fagiuoli, Stefano Pasulo, Luisa Bruno, Raffaele Andreone, Pietro Loggi, Elisabetta Arena, Fabio Rossolini, Gian Maria Sganga, Gabriele Cozza, Valerio TI Infections and Organ Transplantation: New Challenges for Prevention and Treatment-A Colloquium SO TRANSPLANTATION LA English DT Article ID EPSTEIN-BARR-VIRUS; HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; B SURFACE-ANTIGEN; RESISTANT ACINETOBACTER-BAUMANNII; HIV-POSITIVE PATIENTS; CYTOTOXIC T-CELLS; ORTHOTOPIC LIVER-TRANSPLANTATION; ACTIVE ANTIRETROVIRAL THERAPY; RENAL-ALLOGRAFT RECIPIENTS C1 [Grossi, Paolo A.] Univ Insubria, Dept Infect Dis, Varese, Italy. [Grossi, Paolo A.] Natl Ctr Transplantat, ISMETT UPMC Palermo, Rome, Italy. [Costa, Alessandro Nanni; Fehily, Deirdre] Italian Natl Transplant Ctr, Rome, Italy. [Blumberg, Emily A.] Univ Penn, Dept Med, Div Infect Dis, Perelman Sch Med,Hosp Univ Penn, Philadelphia, PA 19104 USA. [Kuehnert, Matthew J.] Ctr Dis Control & Prevent, Off Blood Organ & Other Tissue Safety, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA. [Ison, Michael G.] NW Mem Hosp, Div Infect Dis, Chicago, IL 60611 USA. [Ison, Michael G.] Div Organ Transplantat, Chicago, IL USA. [Lattes, Roberta] Inst Nefrol Nephrol, Dept Transplantat, Infect Dis Unit, Buenos Aires, DF, Argentina. [Kotton, Camille N.] Massachusetts Gen Hosp, Transplant Infect Dis & Compromised Host Program, Div Infect Dis, Boston, MA 02114 USA. [Kotton, Camille N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lilleri, Daniele; Gerna, Giuseppi] Fdn IRCCS Policlin San Matteo, Area Trapiantol, Lab Sperimentali Ric, Pavia, Italy. [Kabanova, Anne; Lanzavecchia, Antonio] IRB, Bellinzona, Switzerland. [Razonable, Raymund R.] Mayo Clin, Coll Med, Div Infect Dis, Rochester, MN USA. [Comoli, Patrizia; Zecca, Marco; Basso, Sabrina] Fdn IRCCS Policlin S Matteo, Pediat Hematol Oncol & Res Labs, Pavia, Italy. [Ginevri, Fabrizio] G Gaslini Inst Children, Dept Nephrol, Clin & Expt Kidney Transplantat Unit, Genoa, Italy. [Grossi, Alessandra] Univ Svizzera Italiana, Fac Commun Sci, ICP, Lugano, Switzerland. [Schena, Francesco P.] Univ Bari, Dept Emergency & Transplantat, Nephrol Dialysis & Transplantat Unit, Bari, Italy. [Rimola, Antoni] Hosp Clin Barcelona, Liver Unit, IDIBAPS, CIBEREHD, Barcelona, Spain. [Burra, Patrizia; De Martin, Elenora; Rodriguez-Castro, Kryssia Isabel] Univ Hosp, Gastroenterol Multivisceral Transplant Unit, Dept Surg & Gastroenterol Sci, Padua, Italy. [Fagiuoli, Stefano; Pasulo, Luisa] OO RR, Gastroenterol & Liver Transplant Unit, Bergamo, Italy. [Bruno, Raffaele] Univ Pavia, Dept Infect Dis, IRCCS San Matteo Hosp, I-27100 Pavia, Italy. [Andreone, Pietro; Loggi, Elisabetta] Univ Bologna, Dept Clin Med, Bologna, Italy. [Arena, Fabio; Rossolini, Gian Maria] Univ Siena, Dept Biotechnol, Microbiol Sect, I-53100 Siena, Italy. [Sganga, Gabriele] Catholic Univ, Dept Gen Surg, Div Gen Surg & Organ Transplantat, Rome, Italy. [Cozza, Valerio] Univ Roma La Sapienza, Dept Surg, Rome, Italy. RP Grossi, PA (reprint author), Univ Insubria, Dept Infect Dis, Varese, Italy. EM paolo.grossi@uninsubria.it; blumbere@mail.med.upenn.edu; mgison@northwestern.edu; roberta.lattes@gmail.com; ckotton@partners.org; pcomoli@smatteo.pv.it; fp.schena@nephro.uniba.it; arimola@clinic.ub.es; burra@unipd.it; sfagiuoli@ospedaliriuniti.bergamo.it; pietro.andreone@unibo.it RI GROSSI, PAOLO/A-6158-2013; Schena, Francesco /K-6982-2016; Lilleri, Daniele/K-7776-2016 OI Schena, Francesco /0000-0001-7927-5207; NR 334 TC 12 Z9 12 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 2012 VL 93 IS 5 SU S BP S4 EP S39 PG 36 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 906FE UT WOS:000301329500002 PM 22374265 ER PT J AU Cassier, PA Gelderblom, H Stacchiotti, S Thomas, D Maki, RG Kroep, JR van der Graaf, WT Italiano, A Seddon, B Domont, J Bompas, E Wagner, AJ Blay, JY AF Cassier, Philippe A. Gelderblom, Hans Stacchiotti, Silvia Thomas, David Maki, Robert G. Kroep, Judith R. van der Graaf, Winette T. Italiano, Antoine Seddon, Beatrice Domont, Julien Bompas, Emanuelle Wagner, Andrew J. Blay, Jean-Yves TI Efficacy of imatinib mesylate for the treatment of locally advanced and/or metastatic tenosynovial giant cell tumor/pigmented villonodular synovitis SO CANCER LA English DT Article DE tenosynovial giant cell tumor; pigmented villonodular synovitis; drug therapy; imatinib; colony-stimulating factor 1; colony-stimulating factor 1 receptor ID GASTROINTESTINAL STROMAL TUMORS; TRANSLOCATION; EXPRESSION; RECEPTOR; SARCOMA; DIFFUSE; CSF1; FMS AB BACKGROUND: Pigmented villonodular synovitis (PVNS) (also known as diffuse-type giant cell tumor) and tenosynovial giant cell tumors (TGCT) are rare, usually benign neoplasms that affect the synovium and tendon sheaths in young adults. These tumors are driven by the overexpression of colony stimulating factor-1 (CSF1). CSF1 is expressed by a minority of tumor cells, which, in turn attract non-neoplastic inflammatory cells that express CSF1 receptor (CSF1R) through a paracrine effect. METHODS: Imatinib mesylate (IM) blocks CSF1R, and previous case reports indicated that it also exerts antitumor activity in PVNS. The authors conducted a multi-institutional retrospective study to assess the activity of IM in patients with locally advanced/ metastatic PVNS/ TGCT. RESULTS: Twenty-nine patients from 12 institutions in Europe, Australia, and the United States were included. There were 13 men, the median age was 41 years, and the most common site of disease was the knee (n 17; 59%). Two patients had metastatic disease to the lung and/ or bone. Five of 27 evaluable patients had Response Evaluation in Solid Tumor (RECIST) responses (overall response rate, 19%; 1 complete response and 4 partial responses), and 20 of 27 patients (74%) had stable disease. Symptomatic improvement was noted in 16 of 22 patients (73%) who were assessable for symptoms. Despite a high rate of symptomatic improvement and a favorable safety profile, 6 patients discontinued because of toxicity, and 4 patients decided to discontinue IM for no clear medical reason. CONCLUSIONS: IM displayed interesting activity in patients with PVNS/ TGCT, providing proof of concept for targeting CSF1R in this disease. The authors concluded that the benefits of alleviating morbidity in patients with localized PVNS/ TGCT must be balanced against the potential toxicity of chronic drug therapy. Cancer 2012; 118: 1649-55. VC 2011 American Cancer Society. C1 [Cassier, Philippe A.; Blay, Jean-Yves] Ctr Leon Berard, Dept Med, F-69008 Lyon, France. [Gelderblom, Hans; Kroep, Judith R.] Leiden Univ, Med Ctr, Dept Med Oncol, Leiden, Netherlands. [Stacchiotti, Silvia] Natl Canc Inst, Dept Canc Med, I-20133 Milan, Italy. [Thomas, David] Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Vic, Australia. [Maki, Robert G.] Mem Sloan Kettering Canc Ctr, Sarcoma Program, New York, NY 10021 USA. [van der Graaf, Winette T.] Radboud Univ Nijmegen, Med Ctr, Dept Med Oncol, NL-6525 ED Nijmegen, Netherlands. [Italiano, Antoine] Bergonie Inst, Dept Med Oncol, Bordeaux, France. [Seddon, Beatrice] Univ Coll London Hosp, Dept Oncol, London, England. [Domont, Julien] Inst Gustave Roussy, Dept Med, Villejuif, France. [Bompas, Emanuelle] Rene Gauducheau Canc Ctr, Dept Med Oncol, Nantes, France. [Wagner, Andrew J.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Blay, Jean-Yves] Univ Lyon, Villeurbanne, France. RP Cassier, PA (reprint author), Ctr Leon Berard, Dept Med, 28 Rue Laennec, F-69008 Lyon, France. EM cassierp@hotmail.com RI van der Graaf, Winette/A-5006-2014; Blay, Jean-Yves/N-3966-2016; Stacchiotti, Silvia/C-2017-2017 OI Blay, Jean-Yves/0000-0001-7190-120X; Stacchiotti, Silvia/0000-0002-1742-8666 FU Fondation de France; Federation des Centres de Luttes Contre le Cancer FX P.A.C. was supported by a grant from the Fondation de France and the Federation des Centres de Luttes Contre le Cancer. NR 18 TC 61 Z9 62 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAR 15 PY 2012 VL 118 IS 6 BP 1649 EP 1655 DI 10.1002/cncr.26409 PG 7 WC Oncology SC Oncology GA 901NE UT WOS:000300973000021 PM 21823110 ER PT J AU Ponce, NA Tsui, J Knight, SJ Afable-Munsuz, A Ladabaum, U Hiatt, RA Haas, JS AF Ponce, Ninez A. Tsui, Jennifer Knight, Sara J. Afable-Munsuz, Aimee Ladabaum, Uri Hiatt, Robert A. Haas, Jennifer S. TI Disparities in cancer screening in individuals with a family history of breast or colorectal cancer SO CANCER LA English DT Article DE family history; cancer screening; cancer disparities; breast cancer; colorectal cancer ID AFRICAN-AMERICAN WOMEN; SERVICES TASK-FORCE; RISK-ASSESSMENT; RECOMMENDATION STATEMENT; ETHNIC-DIFFERENCES; OVARIAN-CANCER; MAMMOGRAPHY; BARRIERS; AVERAGE; VALIDATION AB BACKGROUND: Understanding racial/ethnic disparities in cancer screening by family history risk could identify critical opportunities for patient and provider interventions tailored to specific racial/ethnic groups. The authors evaluated whether breast cancer (BC) and colorectal cancer (CRC) disparities varied by family history risk using a large, multiethnic population-based survey. METHODS: By using the 2005 California Health Interview Survey, BC and CRC screening were evaluated separately with weighted multivariate regression analyses, and stratified by family history risk. Screening was defined for BC as mammogram within the past 2 years for women aged 40 to 64 years; for CRC, screening was defined as annual fecal occult blood test, sigmoidoscopy within the past 5 years, or colonoscopy within the past 10 years for adults aged 50 to 64 years. RESULTS: The authors found no significant BC screening disparities by race/ ethnicity or income in the family history risk groups. Racial/ ethnic disparities were more evident in CRC screening, and the Latino-white gap widened among individuals with family history risk. Among adults with a family history for CRC, the magnitude of the Latino-white difference in CRC screening ( odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.60) was more substantial than that for individuals with no family history ( OR, 0.74; 95% CI, 0.59-0.92). CONCLUSIONS: Knowledge of their family history widened the Latino-white gap in CRC screening among adults. More aggressive interventions that enhance the communication between Latinos and their physicians about family history and cancer risk could reduce the substantial Latino-white screening disparity in Latinos most susceptible to CRC. Cancer 2012; 118: 1656-63. (C) 2011 American Cancer Society. C1 [Ponce, Ninez A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. [Ponce, Ninez A.; Tsui, Jennifer] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Knight, Sara J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. [Knight, Sara J.; Afable-Munsuz, Aimee; Hiatt, Robert A.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Afable-Munsuz, Aimee] Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA. [Ladabaum, Uri] Stanford Univ, Sch Med, Div Gastroenterol, Stanford, CA 94305 USA. [Hiatt, Robert A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Haas, Jennifer S.] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Ponce, NA (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, 650 Charles Young Dr S, Los Angeles, CA 90095 USA. EM nponce@ucla.edu OI Ponce, Ninez/0000-0001-5151-6718 FU University of California at San Francisco Center for Translational and Policy Research on Personalized Medicine (TRANSPERS)-National Cancer Institute (NCI) [P01 CA 130818, NCI K07 CA100097]; Network for Multicultural Research on Health and Healthcare; Department of Family Medicine; David Geffen School of Medicine; University of California at Los Angeles (UCLA); Robert Wood Johnson Foundation; Harvard Catalyst/Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University FX This study was supported by the University of California at San Francisco Center for Translational and Policy Research on Personalized Medicine (TRANSPERS)-National Cancer Institute (NCI) P01 CA 130818 (principal investigator [PI], K. Phillips), NCI K07 CA100097 (PI, N.A.P.), Network for Multicultural Research on Health and Healthcare, Department of Family Medicine, David Geffen School of Medicine, University of California at Los Angeles (UCLA), funded by the Robert Wood Johnson Foundation, and UCLA Summer Graduate Research Mentorship Program. This research was also conducted with support from the Health Disparities Research Program of Harvard Catalyst/Harvard Clinical and Translational Science Center (NIH award #UL1 RR 025758 to J.S.H. and financial contributions from Harvard University and its affiliated academic health care centers). NR 52 TC 16 Z9 16 U1 3 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAR 15 PY 2012 VL 118 IS 6 BP 1656 EP 1663 DI 10.1002/cncr.26480 PG 8 WC Oncology SC Oncology GA 901NE UT WOS:000300973000022 PM 22009719 ER PT J AU Avruch, J Zhou, DW Bardeesy, N AF Avruch, Joseph Zhou, Dawang Bardeesy, Nabeel TI YAP oncogene overexpression supercharges colon cancer proliferation SO CELL CYCLE LA English DT Review DE YAP; Hippo; intestinal stem cell; beta-catenin; colon cancer; liver cancer ID YES-ASSOCIATED PROTEIN; ORGAN SIZE CONTROL; TUMOR-SUPPRESSOR PATHWAY; HIPPO PATHWAY; WW DOMAIN; TRANSCRIPTIONAL COACTIVATOR; HEPATOCELLULAR-CARCINOMA; CELL-PROLIFERATION; GROWTH-CONTROL; STEM-CELLS AB The transcriptional co-activator YAP is an evolutionarily conserved regulator of organ size and progenitor cell proliferation. YAP is overexpressed at high frequency in many common human cancers and can directly drive cancer development in mouse models. YAP abundance and nuclear localization are negatively regulated by the Hippo kinase cascade, which, in epithelia, is activated by physiological cell-cell contact. Recent work in intestinal epithelium has established that YAP is constitutively inhibited by the Hippo pathway and entirely dispensable for normal development and homeostasis. YAP serves only in a standby capacity; should cell-cell contact be abrogated, as after intestinal damage, the loss of Hippo input permits increased YAP abundance and nuclear residence. In turn, YAP cooperates with beta-catenin to transactivate genes that promote stem cell expansion for epithelial repair. This interplay between overexpressed YAP and beta-catenin also drives proliferation of colon cancer cells. The dispensability of YAP in normal intestine makes YAP's expression or outputs attractive targets for cancer therapy. C1 [Avruch, Joseph] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Avruch, Joseph] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Bardeesy, Nabeel] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Avruch, Joseph; Bardeesy, Nabeel] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Zhou, Dawang] Xiamen Univ, Sch Life Sci, State Key Lab Stress Cell Biol, Xiamen, Fujian, Peoples R China. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM avruch@molbio.mgh.harvard.edu OI Zhou, Dawang/0000-0002-9053-5249 FU NIH [DK17776, CA136567]; Sidney Kimmel Foundation for Cancer Research; Linda J. Verville Cancer Research Foundation; 111 Project of Education of China [B06016]; Fundamental Research Funds for the Central Universities of China [2010111079]; National Natural Science Foundation of China [81101503]; Natural Science Foundation of Fujian [2011J05096] FX The work cited herein from the au labs was supported by NIH grants DK17776 (J.A.) and CA136567 (to J.A. and N.B.), the Sidney Kimmel Foundation for Cancer Research (N.B.), the Linda J. Verville Cancer Research Foundation (N.B.), 111 Project of Education of China (NO. B06016, D.Z.), the Fundamental Research Funds for the Central Universities of China (NO. 2010111079, D.Z.), National Natural Science Foundation of China (NO. 81101503, D.Z.) and Natural Science Foundation of Fujian (NO. 2011J05096, D.Z.). NR 80 TC 38 Z9 41 U1 2 U2 23 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 15 PY 2012 VL 11 IS 6 BP 1090 EP 1096 DI 10.4161/cc.11.6.19453 PG 7 WC Cell Biology SC Cell Biology GA 913DD UT WOS:000301851700013 PM 22356765 ER PT J AU Kim, J Kim, WJ Liu, ZQ Loda, MF Freeman, MR AF Kim, Jayoung Kim, Wun-Jae Liu, Zhiqian Loda, Massimo F. Freeman, Michael R. TI The ubiquitin-specific protease USP2a enhances tumor progression by targeting cyclin A1 in bladder cancer SO CELL CYCLE LA English DT Article DE USP2a; cyclin A1; bladder cancer; cisplatin resistance; deubiquitination ID FATTY-ACID SYNTHASE; DEUBIQUITINATING ENZYME USP2A; GROWTH-FACTOR; PROSTATE-CANCER; CELL-CYCLE; AURORA-A; ANTIPROLIFERATIVE FACTOR; UROTHELIAL CANCER; CARCINOMA CELLS; DOWN-REGULATION AB The deubiquitinating enzyme USP2a has shown oncogenic properties in many cancer types by impairing ubiquitination of FASN, MDM2, MDMX or Aurora A. Aberrant expression of USP2a has been linked to progression of human tumors, particularly prostate cancer. However, little is known about the role of USP2a or its mechanism of action in bladder cancer. Here, we provide evidence that USP2a is an oncoprotein in bladder cancer cells. Enforced expression of USP2a caused enhanced proliferation, invasion, migration and resistance to several chemotherapeutic reagents, while USP2a loss resulted in slower proliferation, greater chemosensitivity and reduced migratory/invasive capability compared with control cells. USP2a, but not a catalytically inactive mutant, enhanced proliferation in immortalized TRT-HU1 normal human bladder epithelial cells. USP2a bound to cyclin A1 and prevented cyclin A1 ubiquitination, leading to accumulation of cyclin A1 by a block in degradation. Enforced expression of wild-type USP2a, but not an inactive USP2a mutant, resulted in cyclin A1 accumulation and increased cell proliferation. We conclude that USP2a impairs ubiquitination and stabilizes an important cell cycle regulator, cyclin A1, raising the possibility of USP2a targeting as a therapeutic strategy against bladder tumors in combination with chemotherapy. C1 [Kim, Jayoung; Freeman, Michael R.] Cedars Sinai Med Ctr, Div Canc Biol & Therapeut, Dept Surg, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Kim, Jayoung; Freeman, Michael R.] Cedars Sinai Med Ctr, Dept Biomed Sci, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. [Kim, Jayoung; Freeman, Michael R.] Childrens Hosp, Urol Dis Res Ctr, Boston, MA 02115 USA. [Kim, Jayoung; Freeman, Michael R.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Kim, Jayoung; Freeman, Michael R.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kim, Wun-Jae] Chungbuk Natl Univ, Dept Urol, Cheongju, Chungbuk, South Korea. [Kim, Wun-Jae] Chungbuk Natl Univ, Chungbuk Biomed Sci Ctr BK21, Sch Med, Cheongju, Chungbuk, South Korea. [Liu, Zhiqian; Loda, Massimo F.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Loda, Massimo F.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Loda, Massimo F.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. RP Kim, J (reprint author), Cedars Sinai Med Ctr, Div Canc Biol & Therapeut, Dept Surg, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. EM Jayoung.Kim@cshs.org FU NIH [R01 DK087806, R01 CA143777, P50 DK65298]; Fishbein Family IC Research Foundation/Interstitial Cystitis Association (ICA); ICA; New York Academy of Medicine; Children's Hospital Boston FX We thank Dr. Leland W. Chung (Cedars-Sinai Medical Center) for critical review of the manuscript and helpful advice. This work was supported by the following funding sources: NIH grants R01 DK087806, R01 CA143777 and P50 DK65298 (to M. R. F.); the Fishbein Family IC Research Foundation/Interstitial Cystitis Association (ICA), Pilot Research Program/ICA, New York Academy of Medicine and Children's Hospital Boston Faculty Development (to J.K.). J.K. is an American Urological Association Foundation Research Scholar and a Harvard Medical School Eleanor and Miles Shore Scholar. NR 59 TC 20 Z9 25 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR 15 PY 2012 VL 11 IS 6 BP 1123 EP 1130 DI 10.4161/cc.11.6.19550 PG 8 WC Cell Biology SC Cell Biology GA 913DD UT WOS:000301851700017 PM 22370483 ER PT J AU Santo, L Hideshima, T Kung, AL Tseng, JC Tamang, D Yang, M Jarpe, M van Duzer, JH Mazitschek, R Ogier, WC Cirstea, D Rodig, S Eda, H Scullen, T Canavese, M Bradner, J Anderson, KC Jones, SS Raje, N AF Santo, Loredana Hideshima, Teru Kung, Andrew L. Tseng, Jen-Chieh Tamang, David Yang, Min Jarpe, Matthew van Duzer, John H. Mazitschek, Ralph Ogier, Walter C. Cirstea, Diana Rodig, Scott Eda, Homare Scullen, Tyler Canavese, Miriam Bradner, James Anderson, Kenneth C. Jones, Simon S. Raje, Noopur TI Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma SO BLOOD LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; ENDOPLASMIC-RETICULUM STRESS; DEPENDENT KINASE INHIBITOR; CANCER-THERAPY; DNA-DAMAGE; CELL-DEATH; PHASE-I; PROTEASOME; APOPTOSIS; VORINOSTAT AB Histone deacetylase (HDAC) enzymatic activity has been linked to the transcription of DNA in cancers including multiple myeloma (MM). Therefore, HDAC inhibitors used alone and in combination are being actively studied as novel therapies in MM. In the present study, we investigated the preclinical activity of ACY-1215, an HDAC6-selective inhibitor, alone and in combination with bortezomib in MM. Low doses of ACY-1215 combined with bortezomib triggered synergistic anti-MM activity, resulting in protracted endoplasmic reticulum stress and apoptosis via activation of caspase-3, caspase-8, and caspase-9 and poly (ADP) ribosome polymerase. In vivo, the anti-MM activity of ACY-1215 in combination with bortezomib was confirmed using 2 different xenograft SCID mouse models: human MM injected subcutaneously (the plasmacytoma model) and luciferase-expressing human MM injected intravenously (the disseminated MM model). Tumor growth was significantly delayed and overall survival was significantly prolonged in animals treated with the combination therapy. Pharmacokinetic data showed peak plasma levels of ACY-1215 at 4 hours after treatment coincident with an increase in acetylated alpha-tubulin, a marker of HDAC6 inhibition, by immunohistochemistry and Western blot analysis. These studies provide preclinical rationale for acetylated alpha-tubulin use as a pharmacodynamic biomarker in future clinical trials. (Blood. 2012;119(11):2579-2589) C1 [Santo, Loredana; Eda, Homare; Scullen, Tyler; Canavese, Miriam; Raje, Noopur] Massachusetts Gen Hosp, MGH Canc Ctr, Div Hematol & Oncol, Boston, MA 02114 USA. [Kung, Andrew L.; Tseng, Jen-Chieh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. [Kung, Andrew L.; Tseng, Jen-Chieh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Tamang, David; Yang, Min; Jarpe, Matthew; van Duzer, John H.; Ogier, Walter C.; Jones, Simon S.] Acetylon Pharmaceut, Boston, MA USA. [Mazitschek, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Rodig, Scott] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Raje, N (reprint author), Massachusetts Gen Hosp, MGH Canc Ctr, Div Hematol & Oncol, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org RI perumal, murugiah/D-1565-2012; Mazitschek, Ralph/E-3741-2013; OI Mazitschek, Ralph/0000-0002-1105-689X; Kung, Andrew/0000-0002-9091-488X FU AstraZeneca; Acetylon Pharmaceuticals; Leukemia & Lymphoma Society; Multiple Myeloma Research Foundation FX N.R. is a Leukemia & Lymphoma Society clinical scholar and recipient of the Claflin Distinguished Scholar Award. L.S. is a recipient of the Multiple Myeloma Research Foundation fellow award. K.C.A. is an American Cancer Society clinical research professor.; K.C.A. is an advisor for Celgene, Novartis, Millennium, Onyx, BMS, and Merck and is the founder of Acetylon Pharmaceuticals. T.H., A.L.K, and J.B. are consultants for Acetylon Pharmaceuticals. R.M. is cofounder and member of the scientific advisory board of Acetylon Pharmaceuticals. J.B. is a scientific founder, shareholder, and consultant for Acetylon Pharmaceuticals. M.J., D.T., M.Y., W.C.O., and S.J. are employees of Acetylon Pharmaceuticals. N.R. is on the advisory boards of Celgene, Novartis, Millennium, and Amgen. N.R. has received research funding from AstraZeneca and Acetylon Pharmaceuticals. The remaining authors declare no competing financial interests. NR 43 TC 174 Z9 177 U1 2 U2 45 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 MAR 15 PY 2012 VL 119 IS 11 BP 2579 EP 2589 DI 10.1182/blood-2011-10-387365 PG 11 WC Hematology SC Hematology GA 914HZ UT WOS:000301941700026 PM 22262760 ER PT J AU O'sullivan, JF Leblond, AL Kelly, G Kumar, AHS Metharom, P Buneker, CK Alizadeh-Vikali, N Hynes, BG O'connor, R Caplice, NM AF O'sullivan, J. F. Leblond, A. L. Kelly, G. Kumar, A. H. S. Metharom, P. Buneker, C. K. Alizadeh-Vikali, N. Hynes, B. G. O'connor, R. Caplice, N. M. TI Potent long-term cardioprotective effects of single low dose insulin-like growth factor-1 (LD-IGF-1) treatment post myocardial infarction SO CARDIOVASCULAR RESEARCH LA English DT Meeting Abstract CT 2nd Congress of the European-Society-of-Cardiology Council on Basic Cardiovascular Science - Frontiers in Cardiovascular Biology CY MAR 30-APR 01, 2012 CL London, ENGLAND SP European Soc Cardiol C1 [O'sullivan, J. F.] Mater Misericordiae Univ Hosp, Dublin, Ireland. [Leblond, A. L.; Kumar, A. H. S.; Metharom, P.; Buneker, C. K.; Alizadeh-Vikali, N.; Caplice, N. M.] CRVB, Cork, Ireland. [Kelly, G.; O'connor, R.] Natl Univ Ireland Univ Coll Cork, Cork, Ireland. [Hynes, B. G.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RI O'Connor, Rosemary/B-7902-2014 OI O'Connor, Rosemary/0000-0002-0687-3422 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR 15 PY 2012 VL 93 SU 1 BP S59 EP S59 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 914TQ UT WOS:000301975800241 ER PT J AU Horst, D Chen, J Morikawa, T Ogino, S Kirchner, T Shivdasani, RA AF Horst, David Chen, Justina Morikawa, Teppei Ogino, Shuji Kirchner, Thomas Shivdasani, Ramesh A. TI Differential WNT Activity in Colorectal Cancer Confers Limited Tumorigenic Potential and Is Regulated by MAPK Signaling SO CANCER RESEARCH LA English DT Article ID BETA-CATENIN; STEM-CELLS; COLON-CANCER; TUMOR PROGRESSION; APC; EXPRESSION; MUTATIONS; MARKER; ACTIVATION; MODEL AB Colorectal cancers (CRC) express the WNT effector protein beta-catenin in a heterogeneous subcellular pattern rather than uniformly in the nucleus. In this study, we investigated this important aspect of molecular heterogeneity in CRCs by analyzing its basis and relationship with tumor-initiating capability. CRC cells with the highest WNT levels showed only a marginal increase in tumor initiation capacity. Notably, high WNT activity correlated with a coincident activation of robust mitogen-activated protein kinase (MAPK) signaling, which when upregulated by KRAS expression or downregulated by epidermal growth factor receptor inhibition elicited parallel effects on WNT activity. These findings suggested that on its own high WNT activity may not be a reliable signifier of tumor-initiating potential or stem-like potential. Furthermore, they suggest that MAPK signaling is a. critical modifier of intratumoral heterogeneity that contributes significantly to determining the impact of WNT activity on sternness phenotypes in colon cancer cells. Cancer Res; 72(6); 1547-56. (C) 2012 AACR. C1 [Horst, David; Kirchner, Thomas] LMU, Inst Pathol, D-80337 Munich, Germany. [Horst, David; Chen, Justina; Morikawa, Teppei; Ogino, Shuji; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Horst, David; Chen, Justina; Morikawa, Teppei; Ogino, Shuji; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA USA. RP Horst, D (reprint author), LMU, Inst Pathol, Thalkirchner Str 36, D-80337 Munich, Germany. EM david.horst@med.uni-muenchen.de; ramesh_shivdasani@dfci.harvard.edu FU Harvard Stem Cell Institute; Deutsche Forschungsgemeinschaft; NIH [R01 CA151993, P50CA127003] FX The work was supported by a grant from the Harvard Stem Cell Institute Shivdasani, a fellowship from the Deutsche Forschungsgemeinschaft (D. Horst), and grants R01 CA151993 (S. Ogino) and P50CA127003 from the NIH. NR 40 TC 40 Z9 42 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2012 VL 72 IS 6 BP 1547 EP 1556 DI 10.1158/0008-5472.CAN-11-3222 PG 10 WC Oncology SC Oncology GA 910UC UT WOS:000301667300024 PM 22318865 ER PT J AU O'Dell, MR Huang, JL Whitney-Miller, CL Deshpande, V Rothberg, P Grose, V Rossi, RM Zhu, AX Land, H Bardeesy, N Hezel, AF AF O'Dell, Michael R. Huang, Jing Li Whitney-Miller, Christa L. Deshpande, Vikram Rothberg, Paul Grose, Valerie Rossi, Randall M. Zhu, Andrew X. Land, Hartmut Bardeesy, Nabeel Hezel, Aram F. TI Kras(G12D) and p(53) Mutation Cause Primary intrahepatic Cholangiocarcinoma SO CANCER RESEARCH LA English DT Article ID CHOLANGIOCELLULAR CARCINOMA; HEPATOCELLULAR-CARCINOMA; K-RAS; LIVER; CANCER; PROGRESSION; P16(INK4A); AUTOPHAGY; P53; EXPRESSION AB Intrahepatic cholangiocarcinoma (IHCC) is a primary cancer of the liver with an increasing incidence and poor prognosis. Preclinical studies of the etiology and treatment of this disease are hampered by the relatively small number of available IHCC cell lines or genetically faithful animal models. Here we report the development of a genetically engineered mouse model of IHCC that incorporates two of the most common mutations in human activating mutations of Kras (Kras(G12D)) and deletion of p53. Tissue-specific activation of Kras(G12D) alone resulted in the development of invasive IHCC with low penetrance and long latency. Latency was shortened by combining Kras(G12D)) activation with heterozygous or homozygous deletion of p53 (mean survival of 56 weeks vs. 19 weeks, respectively), which also resulted in widespread local and distant metastasis. Serial analysis showed that the murine models closely recapitulated the multistage histopathologic progression of the human disease, including the development of stroma-rich tumors and the :premalignant biliary lesions, intraductal papillary biliary neoplasms (IPBN), and Von Meyenburg complexes (VMC; also known as biliary hamartomas). These findings establish a new genetically and histo:pathologically faithful model of IHCC and lend experimental support: to the hypothesis that IPBN and VMC are precursors to invasive cancers. Cancer Res; 72(6); 1557-67. (C) 2012 AACR C1 [O'Dell, Michael R.; Huang, Jing Li; Grose, Valerie; Rossi, Randall M.; Hezel, Aram F.] Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Whitney-Miller, Christa L.; Rothberg, Paul] Univ Rochester, Sch Med, Dept Pathol & Lab Med, Rochester, NY 14642 USA. [Land, Hartmut] Univ Rochester, Sch Med, Dept Biomed Genet Med, Rochester, NY USA. [Zhu, Andrew X.; Bardeesy, Nabeel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Hezel, AF (reprint author), Univ Rochester, Sch Med, James P Wilmot Canc Ctr, 300 Elmwood Ave, Rochester, NY 14642 USA. EM Aram_Hezel@URMC.Rochester.edu FU Granara-Skerry Trust; Wilmot Cancer Center at the University of Rochester Medical Center; HHMI; Edelman-Gardner foundation; Target-Cancer Foundation; NUL [1R01CA136567-01A1] FX This work was supported by the Granara-Skerry Trust and was accomplished in the Translational Research Core Facility of the Wilmot Cancer Center at the University of Rochester Medical Center.; A.F. Heed is supported by a HHMI early career award and the Edelman-Gardner foundation award. N. Bardeesy is supported by grants from Target-Cancer Foundation and from the NUL (1R01CA136567-01A1). NR 49 TC 46 Z9 51 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2012 VL 72 IS 6 BP 1557 EP 1567 DI 10.1158/0008-5472.CAN-11-3596 PG 11 WC Oncology SC Oncology GA 910UC UT WOS:000301667300025 PM 22266220 ER PT J AU Koyama, H Zhuang, TG Light, JE Kolla, V Higashi, M McGrady, PW London, WB Brodeur, GM AF Koyama, Hiroshi Zhuang, Tiangang Light, Jennifer E. Kolla, Venkatadri Higashi, Mayumi McGrady, Patrick W. London, Wendy B. Brodeur, Garrett M. TI Mechanisms of CHD5 Inactivation in Neuroblastomas SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; EPITHELIAL OVARIAN-CANCER; PEDIATRIC-ONCOLOGY-GROUP; SQUAMOUS-CELL CARCINOMA; N-MYC AMPLIFICATION; CHROMOSOME 1P; EPIGENETIC INACTIVATION; METHYLATION ANALYSIS; FAVORABLE PROGNOSIS; RISK STRATIFICATION AB Purpose: Neuroblastomas (NBs) have genomic, biological, and clinical heterogeneity. High-risk NBs are characterized by several genomic changes, including MYCN amplification and 1p36 deletion. We identified the chromatin-remodeling gene CHD5 as a tumor suppressor gene that maps to 1p36.31. Low or absent CHD5 expression is associated with a 1p36 deletion and an unfavorable outcome, but the mechanisms of CHD5 inactivation in NBs are unknown. Experimental Design: We examined (i) the CHD5 sequence in 188 high-risk NBs investigated through the TARGET initiative, (ii) the methylation status of the CHD5 promoter in 108 NBs with or without 1p36 deletion and/or MYCN amplification, and (iii) mRNA expression of CHD5 and MYCN in 814 representative NBs using TaqMan low-density array microfluidic cards. Results: We found noexamples of somatically acquired CHD5 mutations, even incases with 1p36 deletion, indicating that homozygous genomic inactivation is rare. Methylation of the CHD5 promoter was common in the high-risk tumors, and it was generally associated with both 1p36 deletion and MYCN amplification. High CHD5 expression was a powerful predictor of favorable outcome, and it showed prognostic value even in multivariable analysis after adjusting for MYCN amplification, 1p36 deletion, and/or 11q deletion. Conclusions: We conclude that (i) somatically acquired CHD5 mutations are rare in primary NBs, so inactivation probably occurs by deletion and epigenetic silencing; (ii) CHD5 expression and promoter methylation are associated with MYCN amplification, suggesting a possible interaction between these 2 genes; and (iii) high CHD5 expression is strongly correlated with favorable clinical/biological features and outcome. Clin Cancer Res; 18(6); 1588-97. (C)2012 AACR. C1 [Koyama, Hiroshi; Zhuang, Tiangang; Light, Jennifer E.; Kolla, Venkatadri; Higashi, Mayumi; Brodeur, Garrett M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Brodeur, Garrett M.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [McGrady, Patrick W.; London, Wendy B.] Stat & Data Ctr, Childrens Oncol Grp, Gainesville, FL USA. [London, Wendy B.] Childrens Hosp, Boston, MA 02115 USA. [London, Wendy B.] Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Brodeur, GM (reprint author), CTRB Rm 3018,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM Brodeur@email.chop.edu FU NIH [R01-CA39771, U10 CA98413]; Alex's Lemonade Stand Foundation; Philadelphia Foundation; TARGET Initiative [NIH U10CA098543]; Audrey E. Evans Chair in Molecular Oncology FX This work was supported, in part, from the NIH (R01-CA39771 to G.M. Brodeur) and (U10 CA98413 to W.B. London), Alex's Lemonade Stand Foundation (to G.M. Brodeur), the Philadelphia Foundation (to G.M. Brodeur), the TARGET Initiative (grant no. NIH U10CA098543, Principal Investigator, John M. Maris), and the Audrey E. Evans Chair in Molecular Oncology (to G.M. Brodeur). NR 53 TC 27 Z9 29 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2012 VL 18 IS 6 BP 1588 EP 1597 DI 10.1158/1078-0432.CCR-11-2644 PG 10 WC Oncology SC Oncology GA 910VW UT WOS:000301672400016 PM 22294723 ER PT J AU Green, MR Rodig, S Juszczynski, P Ouyang, J Sinha, P O'Donnell, E Neuberg, D Shipp, MA AF Green, Michael R. Rodig, Scott Juszczynski, Przemyslaw Ouyang, Jing Sinha, Papiya O'Donnell, Evan Neuberg, Donna Shipp, Margaret A. TI Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin Lymphomas and Posttransplant Lymphoproliferative Disorders: Implications for Targeted Therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID EPSTEIN-BARR-VIRUS; CD8 T-CELLS; LATENT MEMBRANE PROTEIN-1; CLASSICAL HODGKIN; COSTIMULATORY MOLECULE; CLINICAL-SIGNIFICANCE; PANCREATIC-CANCER; STERNBERG CELLS; VIRAL-INFECTION; LIGAND 1 AB Purpose: Programmed cell death ligand 1 (PD-L1) is a molecule expressed on antigen-presenting cells that engages the PD-1 receptor on T cells and inhibits T-cell receptor signaling. The PD-1 axis can be exploited by tumor cells to dampen host antitumor immune responses and foster tumor cell survival. PD-1 blockade has shown promise in multiple malignancies but should be directed toward patients in whom it will be most effective. In recent studies, we found that the chromosome 9p24.1 amplification increased the gene dosage of PD-L1 and its induction by JAK2 in a subset of patients with classical Hodgkin lymphoma (cHL). However, cHLs with normal 9p24.1 copy numbers also expressed detectable PD-L1, prompting analyses of additional PD-L1 regulatory mechanisms. Experimental Design: Herein, we utilized immunohistochemical, genomic, and functional analyses to define alternative mechanisms of PD-L1 activation in cHL and additional EBV+ lymphoproliferative disorders. Results: We identified an AP-1-responsive enhancer in the PD-L1 gene. In cHL Reed-Sternberg cells, which exhibit constitutive AP-1 activation, the PD-L1 enhancer binds AP-1 components and increases PD-L1 promoter activity. In addition, we defined Epstein-Barr virus (EBV) infection as an alternative mechanism for PD-L1 induction in cHLs with diploid 9p24.1. PD-L1 was also expressed by EBV-transformed lymphoblastoid cell lines as a result of latent membrane protein 1-mediated, JAK/STAT-dependent promoter and AP-1-associated enhancer activity. In addition, more than 70% of EBV+ posttransplant lymphoproliferative disorders expressed detectable PD-L1. Conclusions: AP-1 signaling and EBV infection represent alternative mechanisms of PD-L1 induction and extend the spectrum of tumors in which to consider PD-1 blockade. Clin Cancer Res; 18(6); 1611-8. (C)2012 AACR. C1 [Green, Michael R.; Juszczynski, Przemyslaw; Ouyang, Jing; O'Donnell, Evan; Neuberg, Donna; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Rodig, Scott; Sinha, Papiya] Brigham & Womens Hosp, Boston, MA 02115 USA. [Green, Michael R.; Rodig, Scott; Juszczynski, Przemyslaw; Ouyang, Jing; Neuberg, Donna; Shipp, Margaret A.] Harvard Univ, Sch Med, Boston, MA USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM margaret_shipp@dfci.harvard.edu RI Green, Michael/F-3482-2013 OI Green, Michael/0000-0001-6309-9472 FU Miller Family Research Fund; NIH [RO1 CA161026] FX The work was supported by funding from the Miller Family Research Fund and the NIH (RO1 CA161026). NR 49 TC 129 Z9 132 U1 3 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2012 VL 18 IS 6 BP 1611 EP 1618 DI 10.1158/1078-0432.CCR-11-1942 PG 8 WC Oncology SC Oncology GA 910VW UT WOS:000301672400018 PM 22271878 ER PT J AU He, M Capelletti, M Nafa, K Yun, CH Arcila, ME Miller, VA Ginsberg, MS Zhao, BS Kris, MG Eck, MJ Janne, PA Ladanyi, M Oxnard, GR AF He, Mai Capelletti, Marzia Nafa, Khedoudja Yun, Cai-Hong Arcila, Maria E. Miller, Vincent A. Ginsberg, Michelle S. Zhao, Binsheng Kris, Mark G. Eck, Michael J. Jaenne, Pasi A. Ladanyi, Marc Oxnard, Geoffrey R. TI EGFR Exon 19 Insertions: A New Family of Sensitizing EGFR Mutations in Lung Adenocarcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITOR; GENE-MUTATIONS; POSTOPERATIVE RECURRENCE; GEFITINIB TREATMENT; TUMOR RESPONSE; T790M MUTATION; CANCER; SENSITIVITY; GUIDELINES AB Purpose: Epidermal growth factor receptor (EGFR) genotyping is now standard in the management of advanced lung adenocarcinoma, as this biomarker predicts marked benefit from treatment with EGFR tyrosine kinase inhibitors (TKI). EGFR exon 19 insertions are a poorly described family of EGFR mutations, and their association with EGFR-TKI sensitivity in lung adenocarcinoma is uncertain. Experimental Design: Patients with lung cancers harboring EGFR exon 19 insertions were studied. The predicted effects of the insertions on the structure of the EGFR protein were examined, and EGFR exon 19 insertions were introduced into Ba/F3 cells to assess oncogenicity and in vitro sensitivity to EGFR-TKIs. In patients receiving TKI, response magnitude was assessed with serial computed tomographic (CT) measurement. Results: Twelve tumors harboring EGFR exon 19 insertions were identified; patients were predominately female (92%) and never-smokers (75%). The 11 specimens available for full sequencing all showed an 18-bp insertion that resulted in the substitution of a Pro for Leu at residue 747. The mutant EGFR transformed the Ba/F3 cells, which were then sensitive to EGFR-TKI. Six patients with measurable disease received TKI and five had a response on serial CT. Conclusions: EGFR exon 19 insertions are a newly appreciated family of EGFR-TKI-sensitizing mutations, and patients with tumors harboring these mutations should be treated with EGFR-TKI. While these mutations may be missed through the use of some mutation-specific assays, the addition of PCR product size analysis to multigene assays allows sensitive detection of both exon 19 insertion and deletion mutations. Clin Cancer Res; 18(6); 1790-7. (C) 2011 AACR. C1 [He, Mai; Nafa, Khedoudja; Arcila, Maria E.; Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Dept Pathol, Mol Diagnost Serv, New York, NY 10065 USA. [Miller, Vincent A.; Kris, Mark G.] Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10065 USA. [Ginsberg, Michelle S.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Zhao, Binsheng] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10065 USA. [Ladanyi, Marc] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Kris, Mark G.] Weill Cornell Med Coll, New York, NY USA. [Capelletti, Marzia; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Yun, Cai-Hong; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Yun, Cai-Hong; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA. [Jaenne, Pasi A.; Oxnard, Geoffrey R.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Ladanyi, M (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, Mol Diagnost Serv, 1275 York Ave, New York, NY 10065 USA. EM ladanyim@mskcc.org OI Kris, Mark/0000-0002-7317-5341 FU National Cancer Institute [P01-CA129243, P50-CA090578, R01-CA114465] FX The work was supported by the National Cancer Institute grants P01-CA129243 (M. Ladanyi and M.G. Kris) and P50-CA090578 and R01-CA114465 (P.A. Janne) NR 42 TC 51 Z9 56 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2012 VL 18 IS 6 BP 1790 EP 1797 DI 10.1158/1078-0432.CCR-11-2361 PG 8 WC Oncology SC Oncology GA 910VW UT WOS:000301672400036 PM 22190593 ER PT J AU Schwab, J Gasbarrini, A Bandiera, S Boriani, L Amendola, L Picci, P Ferrari, S Boriani, S AF Schwab, Joseph Gasbarrini, Alessandro Bandiera, Stefano Boriani, Luca Amendola, Luca Picci, Piero Ferrari, Stefano Boriani, Stefano TI Osteosarcoma of the Mobile Spine SO SPINE LA English DT Article DE en bloc resection; mobile spine; osteosarcoma ID OSTEOGENIC-SARCOMA; EXPERIENCE; CHEMOTHERAPY AB Study Design. Retrospective case series. Objective. Our goal was to assess whether en bloc resection had an impact on survival. Summary of Background Data. Osteogenic sarcoma occurs rarely in the mobile spine, but when it does, the prognosis is poor. Wide resection is recommended for osteogenic sarcoma of the extremities, but wide resection is difficult and often dangerous in the spine. The goal of this study was to examine whether en bloc removal of osteogenic sarcomas in the mobile spine improves survival. Methods. We performed a retrospective review of all cases of high-grade, osteogenic sarcoma of the mobile spine treated with high-dose methotrexate and adrimaycin-based chemotherapy between 1985 through 2005. There were 9 male patients and 8 female patients. Patients were followed for a median of 38 months or until death, and surviving patients were followed for a minimum of 6.4 years. Patients were grouped on the basis of whether they underwent en bloc spondylectomy. The Enneking stage and Weinstein, Boriani, and Biagini stage, as well as the pre- and postoperative Frankel grades, were collected on all patients. Local recurrence and metastasis data were collected for all patients. Overall survival was calculated using Kaplan-Meier methods with the log rank test utilized to evaluate the effect of en bloc resection on survival. Results. Twelve (71%) of 17 patients with osteogenic sarcoma of the mobile spine died. Median disease-specific survival for the entire cohort was 38.1 months (standard error 29.6; 95% confidence interval 0-96). Nine patients underwent en bloc resection. Median overall survival for patients after en bloc resection was 77.3 months (standard error 62; 95% confidence interval 96) versus 17 months (standard error 6.5; 95% confidence interval 4-29.6) (P = 0.09). Eleven (65%)of 17 patients developed pulmonary metastasis, and 9 of those 11 died from their disease (P = 0.04). Six (35%) patients developed a local recurrence, and all 6 died from their disease (P = 0.07). Conclusion. Osteogenic sarcoma of the mobile spine presents a signifi cant challenge, and most patients die from their disease in spite of aggressive surgery and chemotherapy. Metastastic disease is associated with a worse prognosis. There is a trend toward improved survival with en bloc resection when compared with intralesional resection. Osteogenic sarcoma of the mobile spine is rare and historically has a very poor prognosis. We reviewed our cases of osteogenic sarcoma of the mobile spine to assess whether modern en bloc resection improved survival. Survival remains poor, but there is a trend toward improved survival with en bloc resection. C1 [Schwab, Joseph] Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. [Gasbarrini, Alessandro; Bandiera, Stefano; Boriani, Luca; Amendola, Luca; Boriani, Stefano] Univ Bologna, Dept Med Oncol, Rizzoli Inst, Bologna, Italy. [Picci, Piero] Univ Bologna, Rizzoli Inst, Expt Oncol Lab, Bologna, Italy. [Ferrari, Stefano] Univ Bologna, Rizzoli Inst, Dept Orthoped Oncol & Degenerat Spine Surg, Bologna, Italy. RP Schwab, J (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Yawkey 3,55 Fruit St, Boston, MA 02114 USA. EM schwabj36@gmail.com RI Picci, Piero/J-5979-2016; OI Picci, Piero/0000-0002-8519-4101; Amendola, Luca/0000-0003-2052-4437 NR 17 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAR 15 PY 2012 VL 37 IS 6 BP E381 EP E386 DI 10.1097/BRS.0b013e31822fb1a7 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 912CN UT WOS:000301772300004 PM 22422440 ER PT J AU Ayala, R Kett, LR Leach, TL Young, AB Dunah, AW Orlando, LR AF Ayala, Ramses Kett, Lauren R. Leach, Tiffany L. Young, Anne B. Dunah, Anthone W. Orlando, Lianna R. TI Metabotropic glutamate receptor 1 (mGluR1): Antibody specificity and receptor expression in cultured primary neurons SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Metabotropic glutamate receptors; mGluR1; Neuronal culture; Antibody specificity; Western blot; Immunocytochemistry ID IMMUNOHISTOCHEMICAL LOCALIZATION; GROUP-I; PHOSPHORYLATION; EXCITOTOXICITY AB The availability of high quality, well-characterized antibodies for molecular and cellular neuroscience studies is important. However, not all available antibodies are rigorously evaluated, nor are limitations of particular antibodies often reported. We have examined a panel of currently available mGluR1 antibodies and have identified which ones are selective for use by western blots and immunocytochemistry. We have also specifically determined whether the antibodies cross-react to recognize mGluR5, by examining (1) tissue from both mGluR1 and mGluR5 knock-out mice and (2) primary cortical cultures, in which mGluR5 is widely expressed but mGluR1 is not. Together, these data provide a baseline characterization of antibodies that can and cannot be reliably used in these types of studies, and will hopefully facilitate and positively impact the research efforts of others studying mGluR1. (C) 2011 Elsevier B.V. All rights reserved. C1 [Ayala, Ramses; Kett, Lauren R.; Leach, Tiffany L.; Young, Anne B.; Dunah, Anthone W.; Orlando, Lianna R.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, Boston, MA 02129 USA. [Young, Anne B.; Dunah, Anthone W.; Orlando, Lianna R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Orlando, LR (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Dept Neurol, 114 16th St B114-2000, Boston, MA 02129 USA. EM lianna_orlando@post.harvard.edu FU National Institute of Health [AG13617, NS049006]; Harvard NeuroDiscovery Center FX We thank F. Ferraguti for sharing valuable insight about different mGluR1 antibodies he has worked with, and R. Shigemoto for providing us with his selective mGluR1a antibody. We also thank Y. Xu and M. Schwarzschild for the mGluR5 knock-out mice. This work was supported by National Institute of Health Grants AG13617 (ABY) and NS049006 (AWD), and the Harvard NeuroDiscovery Center (formerly the Harvard Center for Neurodegeneration and Repair) (LRO). NR 20 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAR 15 PY 2012 VL 204 IS 2 BP 221 EP 226 DI 10.1016/j.jneumeth.2011.11.014 PG 6 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 910BR UT WOS:000301612700002 PM 22155385 ER PT J AU Wang, R Zhu, JH Dong, XC Shi, ML Lu, CF Springer, TA AF Wang, Rui Zhu, Jianghai Dong, Xianchi Shi, Minlong Lu, Chafen Springer, Timothy A. TI GARP regulates the bioavailability and activation of TGF beta SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID GROWTH-FACTOR-BETA; T-CELLS; LATENT TGF-BETA-1; EXPRESSION; INTEGRIN; MICE; PROTEIN; BINDING; LYMPHOCYTES; PRECURSOR AB Glycoprotein-A repetitions predominant protein (GARP) associates with latent transforming growth factor-beta (proTGF beta) on the surface of T regulatory cells and platelets; however, whether GARP functions in latent TGF beta activation and the structural basis of coassociation remain unknown. We find that Cys-192 and Cys-331 of GARP disulfide link to the TGF beta 1 prodomain and that GARP with C192A and C331A mutations can also noncovalently associate with proTGF beta 1. Noncovalent association is sufficiently strong for GARP to outcompete latent TGF beta-binding protein for binding to proTGF beta 1. Association between GARP and proTGF beta 1 prevents the secretion of TGF beta 1. Integrin alpha V beta(6) and to a lesser extent alpha V beta(8) are able to activate TGF beta from the GARP-proTGF beta 1 complex. Activation requires the RGD motif of latent TGF beta, disulfide linkage between GARP and latent TGF beta, and membrane association of GARP. Our results show that GARP is a latent TGF beta-binding protein that functions in regulating the bioavailability and activation of TGF beta. C1 [Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Immune Dis Inst, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI shi, minlong/G-8734-2013; Zhu, Jianghai/B-7339-2014; Dong, Xianchi/C-1393-2015 OI Dong, Xianchi/0000-0001-5121-1236 FU National Institutes of Health [HL103526]; GlaxoSmithKline FX This work was supported by National Institutes of Health Grant HL103526 and a fellowship from GlaxoSmithKline. We thank D. Rifkin (New York University) for providing the TMLC cell line, Dean Sheppard (University of California, San Francisco) for the anti-beta6 antibody, Stephen Nishimura (University of California, San Francisco) for the anti-beta8 antibody, Vesna Todorovic (New York University) for the LTBP1 cDNA, and Katri Koli (University of Helsinki) for the TGF beta 1 cDNA. NR 45 TC 44 Z9 46 U1 0 U2 10 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR 15 PY 2012 VL 23 IS 6 BP 1129 EP 1139 DI 10.1091/mbc.E11-12-1018 PG 11 WC Cell Biology SC Cell Biology GA 907XO UT WOS:000301453700029 PM 22278742 ER PT J AU Andrews, JR Noubary, F Walensky, RP Cerda, R Losina, E Horsburgh, CR AF Andrews, Jason R. Noubary, Farzad Walensky, Rochelle P. Cerda, Rodrigo Losina, Elena Horsburgh, C. Robert TI Risk of Progression to Active Tuberculosis Following Reinfection With Mycobacterium tuberculosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID EXOGENOUS REINFECTION; MEDICAL-STUDENTS; INFECTION; PATHOGENESIS; RECURRENCE; EPIDEMICS; IMMUNITY; RELAPSE; DISEASE; TESTS AB Background. The risk of progression to active tuberculosis is greatest in the several years following initial infection. The extent to which latent tuberculosis infection reduces the risk of progressive disease following reexposure and reinfection is not known. Indirect estimates from population models have been highly variable. Methods. We reviewed prospective cohort studies of persons exposed to individuals with infectious tuberculosis that were published prior to the widespread treatment of latent tuberculosis to estimate the incidence of tuberculosis among individuals with latent tuberculosis infection (LTBI group) and without latent tuberculosis (uninfected; UI group). We calculated the incidence rate ratio (IRR) of tuberculosis disease following infection between these 2 groups. We then adjusted incidence for expected reactivation, proportion of each group that was infected, and median time of observation following infection during the study. Results. We identified 18 publications reporting tuberculosis incidence among 23 paired cohorts of individuals with and without latent infection (total N = 19 886). The weighted mean adjusted incidence rate of tuberculosis in the LTBI and UI groups attributable to reinfection was 13.5 per 1000 person-years (95% confidence interval [CI]: 5.0-26.2 per 1000 person-years) and that attributable to primary infection was 60.1 per 1000 person-years (95% CI: 38.6-87.4 per 1000 person-years). The adjusted IRR for tuberculosis in the LTBI group compared with the UI group was 0.21 (95% CI: .14-.30). Conclusions. Individuals with latent tuberculosis had 79% lower risk of progressive tuberculosis after reinfection than uninfected individuals. The risk reduction estimated in this study is greater than most previous estimates made through population models. C1 [Andrews, Jason R.; Noubary, Farzad; Walensky, Rochelle P.; Losina, Elena] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Cerda, Rodrigo] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Horsburgh, C. Robert] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Andrews, JR (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jandrews6@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X; Andrews, Jason/0000-0002-5967-251X FU National Institute of Allergy and Infectious Diseases [R01 AI058736, T32 AI007433-20]; AIDS Clinical Trials Group [U01 AI068636]; Doris Duke Charitable Foundation; National Institute of General Medical Sciences [U54 GM088558] FX This work was supported by the National Institute of Allergy and Infectious Diseases [grants R01 AI058736 and T32 AI007433-20]; the AIDS Clinical Trials Group [grant U01 AI068636]; the Doris Duke Charitable Foundation [Clinical Scientist Development Award]; and the National Institute of General Medical Sciences [grant U54 GM088558] NR 40 TC 80 Z9 80 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2012 VL 54 IS 6 BP 784 EP 791 DI 10.1093/cid/cir951 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 899CK UT WOS:000300790900009 PM 22267721 ER PT J AU Baker, MA Lin, HH Chang, HY Murray, MB AF Baker, Meghan A. Lin, Hsien-Ho Chang, Hsing-Yi Murray, Megan B. TI The Risk of Tuberculosis Disease Among Persons With Diabetes Mellitus: A Prospective Cohort Study SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CLAIMS DATA; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; CARE UTILIZATION; TAIWAN; MICE; SUSCEPTIBILITY; ASSOCIATION; PREVALENCE; INSURANCE AB Background. Evidence suggests a causal link between diabetes mellitus and tuberculosis risk. However, to date, few studies have used a prospective design to estimate the impact of diabetes on tuberculosis in a general population. In this study, we prospectively investigated the risk of tuberculosis among persons with diabetes stratified by severity. Methods. A cohort study was performed that involved 17 715 Taiwanese persons on whom baseline data were collected during Taiwan's 2001 National Health Interview Survey. Participants' subsequent medical care until December 2004 was captured from the National Health Insurance database. The diagnosis and severity of diabetes were established using self-report, International Classification of Diseases, Ninth Revision, Clinical Modification codes, and pharmacy records; incident tuberculosis disease was identified using these codes and pharmacy records. Covariates were obtained through in-person interviews. We used Cox proportional hazards regression analyses to measure the association between tuberculosis and both diabetes and diabetes severity. Results. Diabetes in general and treated diabetes were significantly associated with tuberculosis (adjusted hazard ratio, 2.09 [95% confidence interval {CI}, 1.10-3.95] and 2.60 [95% CI, 1.34-5.03], respectively). Compared with persons without treated diabetes, participants' risk of tuberculosis increased as the number of complications of diabetes mellitus increased (P = .0016), with >3-fold risk among those with >= 2 diabetes-related complications (odds ratio, 3.45; 95% CI, 1.59-7.50). Similarly, the risk increased among those with higher Diabetes Complications Severity Index scores (P = .0002). Conclusions. The risk of developing tuberculosis increased among those with increasing diabetes severity. C1 [Baker, Meghan A.; Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Baker, Meghan A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Murray, Megan B.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Lin, Hsien-Ho] Mennonite Christian Hosp, Dept Community Hlth, Hualien, Taiwan. [Lin, Hsien-Ho] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Taipei 10764, Taiwan. [Chang, Hsing-Yi] Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli, Taiwan. RP Murray, MB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 641 Huntington Ave, Boston, MA 02115 USA. EM mmurray@hsph.harvard.edu RI Chang, Hsing-Yi /E-3973-2010; OI LIN, HSIEN-HO/0000-0002-7481-6016 NR 40 TC 39 Z9 41 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2012 VL 54 IS 6 BP 818 EP 825 DI 10.1093/cid/cir939 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 899CK UT WOS:000300790900015 PM 22238171 ER PT J AU Liu, WT Xiao, X Demirci, G Madsen, J Li, XC AF Liu, Wentao Xiao, Xiang Demirci, Gulcin Madsen, Joren Li, Xian C. TI Innate NK Cells and Macrophages Recognize and Reject Allogeneic Nonself In Vivo via Different Mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; ALLOGRAFT-REJECTION; XENOGRAFT REJECTION; MEDIATED REJECTION; GRAFT-REJECTION; T-CELLS; ACTIVATED MACROPHAGES; TRANSPLANT TOLERANCE; MICE; RECEPTORS AB Both innate and adaptive immune cells are involved in the allograft response. But how the innate immune cells respond to allotrans-plants remains poorly defined. In the current study, we examined the roles of NK cells and macrophages in recognizing and rejecting allogeneic cells in vivo. We found that in naive mice NK cells are the primary effector cells in the killing of allogeneic cells via "missing self" recognition. However, in alloantigen-presensitized mice, NK cells are dispensable. Instead, macrophages become alloreactive and readily recognize and reject allogeneic nonself. This effect requires help from activated CD4(+) T cells and involves CD40/CD40L engagement, because blocking CD40/CD40L interactions prevents macrophage-mediated rejection of allogeneic cells. Conversely, actively stimulating CD40 triggers macrophage-mediated rejection in the absence of CD4(+) T cells. Importantly, alloantigen-primed and CD4(+) T cell-helped macrophages (licensed macrophages) exhibit potent regulatory function in vivo in an acute graft-versus-host disease model. Together, our data uncover an important role for macrophages in the alloimmune response and may have important clinical implications. The Journal of Immunology, 2012, 188: 2703-2711. C1 [Liu, Wentao; Xiao, Xiang; Demirci, Gulcin; Li, Xian C.] Brigham & Womens Hosp, Transplant Res Ctr, Boston, MA 02115 USA. [Liu, Wentao; Xiao, Xiang; Demirci, Gulcin; Li, Xian C.] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA 02115 USA. [Madsen, Joren] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02224 USA. [Madsen, Joren] Harvard Univ, Sch Med, Boston, MA 02224 USA. RP Li, XC (reprint author), Brigham & Womens Hosp, Transplant Res Ctr, 221 Longwood Ave,LM 303, Boston, MA 02115 USA. EM xli28@partners.org OI Li, Xian Chang/0000-0002-5981-2762 FU National Institutes of Health [R01AI080779, R56AI080779, T32AI070085] FX This work was supported by the National Institutes of Health (Grants R01AI080779 and R56AI080779 to X. C. L.). X. X. was supported by Award T32AI070085 from the National Institutes of Health. NR 32 TC 25 Z9 29 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2012 VL 188 IS 6 BP 2703 EP 2711 DI 10.4049/jimmunol.1102997 PG 9 WC Immunology SC Immunology GA 903OD UT WOS:000301126000026 PM 22327074 ER PT J AU Meng, R Ji, XM Dornbos, D Feeney, K Ding, YC Wang, XY AF Meng, Ran Ji, Xunming Dornbos, David, III Feeney, Kathleen Ding, Yuchuan Wang, Xiaoying TI A case of Susac's syndrome in a Chinese male SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Letter C1 [Meng, Ran; Ji, Xunming] Capital Med Univ, Cerebral Vasc Dis Res Inst, Xuanwu Hosp,Chinese Amer United Lab, Key Lab Neurodegenerat Dis,Minist Educ, Beijing 100053, Peoples R China. [Meng, Ran] Peking Univ, Clin Med Coll 9, Capital Med Univ, Dept Neurol,Beijing Shijitan Hosp, Beijing 100038, Peoples R China. [Meng, Ran; Feeney, Kathleen] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dornbos, David, III; Ding, Yuchuan] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI 48201 USA. [Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Ji, XM (reprint author), Capital Med Univ, Cerebral Vasc Dis Res Inst, Xuanwu Hosp,Chinese Amer United Lab, Key Lab Neurodegenerat Dis,Minist Educ, 45 Changchun St, Beijing 100053, Peoples R China. EM jixm@ccmu.edu.cn NR 5 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAR 15 PY 2012 VL 314 IS 1-2 BP 181 EP 182 DI 10.1016/j.jns.2011.11.031 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 905LF UT WOS:000301273000037 PM 22178082 ER PT J AU Wang, LL Neuberg, D Wu, CJ AF Wang, Lili Neuberg, Donna Wu, Catherine J. TI SF3B1 in Chronic Lymphocytic Leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Wang, Lili; Neuberg, Donna; Wu, Catherine J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wang, LL (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM cwu@partners.org NR 0 TC 1 Z9 1 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 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 15 PY 2012 VL 366 IS 11 BP 1057 EP 1058 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 908HZ UT WOS:000301482800016 ER PT J AU Fingold, DR AF Fingold, Diane R. TI The Road Less Traveled Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fingold, DR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 15 PY 2012 VL 366 IS 11 BP 1062 EP 1062 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 908HZ UT WOS:000301482800024 ER PT J AU Mears, RP Spencer, KM AF Mears, Ryan P. Spencer, Kevin M. TI Electrophysiological Assessment of Auditory Stimulus-Specific Plasticity in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Auditory processing; ERP; event-related brain potential; NMDA receptor; plasticity; schizophrenia ID LONG-TERM POTENTIATION; VISUAL-EVOKED POTENTIALS; LTP-LIKE CHANGES; RECEPTOR ANTAGONIST; SENSORY STIMULATION; PLANUM TEMPORALE; HESCHL GYRUS; CORTEX; INDUCTION; COMPONENT AB Background: Disrupted neuroplasticity may be an important aspect of the neural basis of schizophrenia. We used event-related brain potentials (ERPs) to assay neuroplasticity after auditory conditioning in chronic schizophrenia patients (SZ) and matched healthy control subjects (HC). Methods: Subjects (15 HC, 14 SZ) performed an auditory oddball task during electroencephalogram recording before and after auditory tetanic stimulation (Pre/Post Blocks). Each oddball block consisted of 1000-Hz and 1500-Hz standards and 400-Hz targets. During tetanic conditioning, 1000-Hz tones were presented at 11 Hz for 2.4 min. We analyzed the standard trials, comparing the ERPs evoked by the tetanized stimuli (1000 Hz tones: TS+) and untetanized stimuli (1500 Hz tones: TS-) in the Post Blocks with ERPs from the Pre Blocks (averaged into Baseline ERPs). Results: In Post Block 1 in HC, TS+ tones evoked a negative shift (60-350 msec) at right temporal electrodes relative to Baseline. No pre-/post-tetanus effects were found in SZ. In Post Block 2 in HC, TS+ tones evoked a positive shift (200-300 msec) at bilateral frontal electrodes. In SZ, TS+ tones evoked a positive shift (100-400 msec) at right frontotemporal electrodes. No pre-/post-tetanus effects were found in either subject group for the TS-tones. The right temporal Post Block 1 and 2 effects were correlated in SZ, suggesting a trade-off in the expression of these effects. Conclusions: These results suggest that stimulus-specific auditory neuroplasticity is abnormal in schizophrenia. The electrophysiologic assessment of stimulus-specific plasticity may yield novel targets for drug treatment in schizophrenia. C1 [Mears, Ryan P.; Spencer, Kevin M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Res Serv,Dept Psychiat, Boston, MA 02130 USA. RP Spencer, KM (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Res Serv,Dept Psychiat, 150 S Huntington Ave, Boston, MA 02130 USA. EM kevin_spencer@hms.harvard.edu OI Spencer, Kevin/0000-0002-5500-7627 FU U.S. Department of Veterans Affairs [CX000154]; U.S. National Institutes of Health [R03 MH076760, R01 MH080187]; Galenea Inc.; Bristol-Myers Squibb FX This study was supported by grants to KMS from the U.S. Department of Veterans Affairs (Merit Review Award CX000154) and the U.S. National Institutes of Health (Grant Nos. R03 MH076760, R01 MH080187).; RPM reported no biomedical financial interests or potential conflicts of interest. KMS reported receiving consultation fees from Galenea Inc. and Bristol-Myers Squibb. NR 50 TC 17 Z9 17 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 2012 VL 71 IS 6 BP 503 EP 511 DI 10.1016/j.biopsych.2011.12.016 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 899BX UT WOS:000300789100010 PM 22277333 ER PT J AU Cavus, I Reinhart, RMG Roach, BJ Gueorguieva, R Teyler, TJ Clapp, WC Ford, JM Krystal, JH Mathalon, DH AF Cavus, Idil Reinhart, Robert M. G. Roach, Brian J. Gueorguieva, Ralitza Teyler, Timothy J. Clapp, Wesley C. Ford, Judith M. Krystal, John H. Mathalon, Daniel H. TI Impaired Visual Cortical Plasticity in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Evoked potential; long-term potentiation; plasticity; schizophrenia; visual cortex ID LONG-TERM POTENTIATION; PRINCIPAL-COMPONENTS-ANALYSIS; EVOKED POTENTIALS; SYNAPTIC PLASTICITY; CORTEX; IDENTIFICATION; INDUCTION; DEFICITS; CONVERGENCE; STIMULATION AB Background: Impaired cortical plasticity may be part of the core pathophysiology of schizophrenia (SZ). Long-term potentiation is a form of neuroplasticity that has been recently demonstrated in humans by showing that repetitive visual stimulation produces lasting enhancement of visual evoked potentials (VEP). Using this paradigm, we examined whether visual cortical plasticity is impaired in SZ. Methods: Electroencephalographic data were recorded from 19 SZ and 22 healthy control (HC) subjects during a visual long-term potentiation paradigm. Visual evoked potentials were elicited by standard visual stimuli (similar to.83 Hz, 2-minute blocks) at baseline and at 2, 4, and 20 minutes following exposure to visual high-frequency stimulation (HFS) (similar to 8.8 Hz, 2 minutes) designed to induce VEP potentiation. To ensure attentiveness during VEP assessments, subjects responded with a button press to infrequent (10%) target stimuli. Visual evoked potentials were subjected to principal components analysis. Two negative-voltage components prominent over occipital-parietal electrode sites were evident at 92 msec (C1) and at 146 msec (N1b). Changes in C1 and N1b component scores from baseline to the post-HFS assessments were compared between groups. Results: High-frequency stimulation produced sustained potentiation of visual C1 and N1b in HCs but not in SZs. The HCs and SZs had comparable HFS-driven electroencephalographic visual steady state responses. However, greater visual steady state responses to the HFS predicted greater N1b potentiation in HCs but not in SZs. Schizophrenia patients with greater N1b potentiation decreased their reaction times to target stimuli. Conclusions: Visual cortical plasticity is impaired in schizophrenia, consistent with hypothesized deficits in N-methyl-D-aspartate receptor function. C1 [Mathalon, Daniel H.] San Francisco VA Med Ctr, Mental Hlth Serv 116D, San Francisco, CA 94121 USA. [Cavus, Idil; Reinhart, Robert M. G.; Gueorguieva, Ralitza; Ford, Judith M.; Krystal, John H.; Mathalon, Daniel H.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Roach, Brian J.; Ford, Judith M.; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Gueorguieva, Ralitza] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Gueorguieva, Ralitza] Yale Univ, Sch Med, New Haven, CT USA. [Teyler, Timothy J.] Univ Idaho, Washington Wyoming Alaska Montana Idaho Reg Med E, Moscow, ID 83843 USA. [Clapp, Wesley C.] NeuroScouting LLC, Cambridge, MA USA. [Krystal, John H.] Vet Affairs Connecticut Healthcare Syst, Schizophrenia Biol Res Ctr, New Haven, CT USA. [Krystal, John H.] Connecticut Mental Hlth Ctr, Abraham Ribicoff Res Facil, New Haven, CT 06519 USA. RP Mathalon, DH (reprint author), San Francisco VA Med Ctr, Mental Hlth Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM daniel.mathalon@ucsf.edu OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974; Gueorguieva, Ralitza/0000-0003-0944-5973 FU National Institutes of Health-National Institute of Mental Health [1RO1MH06508-01A2]; VA Schizophrenia Biological Research Center; Janssen Research Foundation; AstraZeneca, Inc; Pfizer, Inc. FX This study was funded by National Institutes of Health-National Institute of Mental Health Grant# 1RO1MH06508-01A2 (TT, IC), and by the VA Schizophrenia Biological Research Center (JMF).; Dr. Cavus, is currently employed by Bristol-Myers Squibb, Inc, receives Bristol-Myers Squibb stock options, and reports that her name is included under a provisional patent titled "A noninvasive biomarker of human cortical plasticity and cognition," United States Patent and Trademark Office (USPTO) serial number 61/140,833. Previously she was employed by Pfizer Inc. This work was done during Dr. Cavus' employment at Yale University. Dr. Teyler reportsaconsulting appointment with Pfizer Laboratories and that his name is included under a provisional patent titled " A noninvasive biomarker of human cortical plasticity and cognition," USPTO serial number 61/140,833. Dr. Clapp reports that his name is included under a provisional patent titled " A noninvasive biomarker of human cortical plasticity and cognition," USPTO serial number 61/140,833. Dr. Clapp is currently employed full-time as a co-founder and chief scientist at NeuroScouting LLC. This work was done prior to the founding of NeuroScouting, while at Auckland University and University of California San Francisco. Dr. Krystal reports individual consultant agreements (each less than $10,000 per year) from Aisling Capital, LLC, AstraZeneca Pharmaceuticals, Biocortech, Brintnall & Nicolini, Inc., Easton Associates, Gilead Sciences, Inc., GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck Research USA, Medivation, Inc., Merz Pharmaceuticals, MK Medical Communications, F. Hoffmann-La Roche Ltd, SK Holdings Co., Ltd, Sunovion Pharmaceuticals, Inc., Takeda Industries, and Teva Pharmaceutical Industries, Ltd. Dr. Krystal also reports serving on the Scientific Advisory Boards for Abbott Laboratories, Bristol-Myers Squibb, Eisai, Inc., Eli Lilly and Co., Forest Laboratories, Inc., Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Inc., Naurex, Inc., Pfizer Pharmaceuticals and Shire Pharmaceuticals. Dr. Krystal also reports Exercisable Warrant Options from Tetragenex Pharmaceuticals (value less than $ 150). Dr. Krystal also reports serving on the Board of Directors of the Coalition for Translational Research in Alcohol and Substance Use Disorders. Dr. Krystal also reports receiving research support from Janssen Research Foundation (provided drug and some study support to the Department of Veterans Affairs). Dr. Krystal also reports serving as Editor of Biological Psychiatry, which is associated with income greater than $ 10,000 per year. Dr. Krystal also reports being President for the American College of Neuropsychopharmacology. Dr. Krystal also reports that his name is included on a patent titled "Dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia" (Patent #: 5,447,948, September 5, 1995), and on provisional patents titled "Targeting the glutamatergic system for the treatment of neuropsychiatric disorders" (PCTWO06108055A1) and "Intranasal administration of ketamine to treat depression" (pending). Dr. Mathalon reports research funding from AstraZeneca, Inc, consulting fees from Pfizer, Inc. and that his name is included under a provisional patent titled "A noninvasive biomarker of human cortical plasticity and cognition," USPTO serial number 61/140,833. All other authors report no biomedical financial interests or potential conflicts of interest. NR 68 TC 25 Z9 25 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 2012 VL 71 IS 6 BP 512 EP 520 DI 10.1016/j.biopsych.2012.01.013 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 899BX UT WOS:000300789100011 PM 22364738 ER PT J AU Nguyen, PL Chen, MH Beckman, JA Beard, CJ Martin, NE Choueiri, TK Hu, JC Hoffman, KE Dosoretz, DE Moran, BJ Salenius, SA Braccioforte, MH Kantoff, PW D'Amico, AV Ennis, RD AF Nguyen, Paul L. Chen, Ming-Hui Beckman, Joshua A. Beard, Clair J. Martin, Neil E. Choueiri, Toni K. Hu, Jim C. Hoffman, Karen E. Dosoretz, Daniel E. Moran, Brian J. Salenius, Sharon A. Braccioforte, Michelle H. Kantoff, Philip W. D'Amico, Anthony V. Ennis, Ronald D. TI INFLUENCE OF ANDROGEN DEPRIVATION THERAPY ON ALL-CAUSE MORTALITY IN MEN WITH HIGH-RISK PROSTATE CANCER AND A HISTORY OF CONGESTIVE HEART FAILURE OR MYOCARDIAL INFARCTION SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Androgen deprivation therapy; Prostate cancer; Cardiovascular; Mortality ID CARDIOVASCULAR-DISEASE; SUPPRESSION THERAPY; FOLLOW-UP; RADIOTHERAPY; RADIATION; TRIAL AB Purpose: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease. Methods and Materials: Of 14,594 men with cT1c-T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT. Results: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32-2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17-5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13-2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96-2.43; p = 0.075). Conclusions: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT. (C) 2012 Elsevier Inc. C1 [Nguyen, Paul L.; Beard, Clair J.; Martin, Neil E.; D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Chen, Ming-Hui] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Cardiol, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Hoffman, Karen E.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Dosoretz, Daniel E.; Salenius, Sharon A.] 21st Century Oncol, Ft Myers, FL USA. [Moran, Brian J.; Braccioforte, Michelle H.] Chicago Prostate Ctr, Westmont, IL USA. [Ennis, Ronald D.] Albert Einstein Coll Med, Continuum Canc Ctr New York, St Lukes Roosevelt Hosp, Dept Radiat Oncol, New York, NY USA. [Ennis, Ronald D.] Albert Einstein Coll Med, Continuum Canc Ctr New York, Beth Israel Hosp, Dept Radiat Oncol, New York, NY USA. [Choueiri, Toni K.; Kantoff, Philip W.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Hu, Jim C.] Harvard Univ, Sch Med, Brigham & Womens Faulkner Hosp, Div Urol Surg, Boston, MA USA. RP Nguyen, PL (reprint author), Dana Farber Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu RI Martin, Neil/E-2193-2014; OI Martin, Neil/0000-0002-8164-8516; Beckman, Joshua/0000-0001-8332-8439 NR 20 TC 39 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2012 VL 82 IS 4 BP 1411 EP 1416 DI 10.1016/j.ijrobp.2011.04.067 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 901PW UT WOS:000300980300054 PM 21708431 ER PT J AU Halasz, LM Sreedhara, M Chen, YH Bellon, JR Punglia, RS Wong, JS Harris, JR Brock, JE AF Halasz, Lia M. Sreedhara, Meera Chen, Yu-Hui Bellon, Jennifer R. Punglia, Rinaa S. Wong, Julia S. Harris, Jay R. Brock, Jane E. TI Improved Outcomes of Breast-Conserving Therapy for Patients With Ductal Carcinoma in Situ SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 33rd Annual San Antonio Breast Cancer Symposium CY DEC 08-12, 2010 CL San Antonio, TX SP European Soc Coloproctol (ESCP), Finnish Breast Canc Grp DE DCIS; Breast-conserving therapy; HER-2; Breast-conserving surgery; Adjuvant radiation therapy ID RECURRENCE; HER-2/NEU; EXPRESSION; FEATURES; OVEREXPRESSION; AMPLIFICATION; CANCER AB Purpose: Patients treated for ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) and radiation therapy (RT) at our center from 1976 to 1990 had a 15% actuarial 10-year local recurrence (LR) rate. Since then, improved mammographic and pathologic evaluation and greater attention to achieving negative margins may have resulted in a lower risk of LR. In addition, clinical implications of hormone receptor and HER-2 status in DCIS remain unclear. We sought to determine the following: LR rates with this more modern approach; the relation between LR and HER-2 status; and clinical and pathologic factors associated with HER-2(+) DCIS. Methods and Materials: We studied 246 consecutive patients who underwent BCS and RT for DCIS from 2001 to 2007. Of the patients, 96 (39%) were Grade III and the median number of involved tissue blocks was 3. Half underwent re-excision and 222 (90%) had negative margins (> 2 mm). All received whole-breast RT (40-52 Gy) and 99% (244) received a tumor bed boost (8-18 Gy). Routine estrogen receptor (ER), progesterone receptor (PR), and HER-2 immunohistochemistry was instituted in 2003. Results: With median follow-up of 58 months, there were no LRs. Seven patients (3%) developed contralateral breast cancer (4 invasive and 3 in situ). Among 163 patients with immunohistochemistry, 124 were ER/PR+HER-2(-), 27 were ER/PR+HER-2(+), 6 were ER-/PR-HER-2(+), and 6 were ER-/PR-HER-2(-). On univariable analysis, HER-2(+) was significantly associated with Grade III, ER-/PR-, central necrosis, comedo subtype, more extensive DCIS, and postmenopausal status. On multivariable analysis, Grade III and postmenopausal status remained significantly associated with HER-2(+). Conclusions: In an era of mammographically identified DCIS, larger excisions, widely negative margins and the use of a tumor bed boost, we observed no LR regardless of ER/PR/HER-2 status. Factors associated with HER-2(+)DCIS included more extensive DCIS, Grade III, ER-/PR-, central necrosis, comedo subtype, and postmenopausal status. Further follow-up and additional studies are required to confirm these results. (C) 2012 Elsevier Inc. C1 [Brock, Jane E.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Halasz, Lia M.] Harvard Radiat Oncol Program, Boston, MA USA. [Sreedhara, Meera; Bellon, Jennifer R.; Punglia, Rinaa S.; Wong, Julia S.; Harris, Jay R.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Sreedhara, Meera; Bellon, Jennifer R.; Punglia, Rinaa S.; Wong, Julia S.; Harris, Jay R.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Brock, JE (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jebrock@partners.org NR 19 TC 19 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2012 VL 82 IS 4 BP E581 EP E586 DI 10.1016/j.ijrobp.2011.08.015 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 901PW UT WOS:000300980300001 PM 22208975 ER PT J AU Kotton, CN AF Kotton, Camille N. TI Preventative Tools of the Future: Predicting the Individual Risk of Cytomegalovirus Infection After Transplant SO TRANSPLANTATION LA English DT Editorial Material ID RECIPIENTS C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Kotton, CN (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Cox 5, Boston, MA 02114 USA. EM ckotton@partners.org NR 7 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 2012 VL 93 IS 5 BP 467 EP 468 DI 10.1097/TP.0b013e318242165d PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 899DC UT WOS:000300793700005 PM 22222786 ER PT J AU Busser, BW Shokri, L Jaeger, SA Gisselbrecht, SS Singhania, A Berger, MF Zhou, B Bulyk, ML Michelson, AM AF Busser, Brian W. Shokri, Leila Jaeger, Savina A. Gisselbrecht, Stephen S. Singhania, Aditi Berger, Michael F. Zhou, Bo Bulyk, Martha L. Michelson, Alan M. TI Molecular mechanism underlying the regulatory specificity of a Drosophila homeodomain protein that specifies myoblast identity SO DEVELOPMENT LA English DT Article DE Homeodomain; Myoblast; Gene regulation ID TRANSCRIPTION FACTORS; SEQUENCE LOGOS; HOMEOBOX GENE; HOX PROTEINS; MUSCLE; DNA; MESODERM; DIVERSIFICATION; EXPRESSION; DIFFERENTIATION AB A subfamily of Drosophila homeodomain (HD) transcription factors (TFs) controls the identities of individual muscle founder cells (FCs). However, the molecular mechanisms by which these TFs generate unique FC genetic programs remain unknown. To investigate this problem, we first applied genome-wide mRNA expression profiling to identify genes that are activated or repressed by the muscle HD TFs Slouch (Slou) and Muscle segment homeobox (Msh). Next, we used protein-binding microarrays to define the sequences that are bound by Slou, Msh and other HD TFs that have mesodermal expression. These studies revealed that a large class of HDs, including Slou and Msh, predominantly recognize TAAT core sequences but that each HD also binds to unique sites that deviate from this canonical motif. To understand better the regulatory specificity of an individual FC identity HD, we evaluated the functions of atypical binding sites that are preferentially bound by Slou relative to other HDs within muscle enhancers that are either activated or repressed by this TF. These studies showed that Slou regulates the activities of particular myoblast enhancers through Slou-preferred sequences, whereas swapping these sequences for sites that are capable of binding to multiple HD family members does not support the normal regulatory functions of Slou. Moreover, atypical Slou-binding sites are overrepresented in putative enhancers associated with additional Slou-responsive FC genes. Collectively, these studies provide new insights into the roles of individual HD TFs in determining cellular identity, and suggest that the diversity of HD binding preferences can confer regulatory specificity. C1 [Shokri, Leila; Gisselbrecht, Stephen S.; Berger, Michael F.; Zhou, Bo; Bulyk, Martha L.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Bulyk, Martha L.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol HST, Boston, MA 02115 USA. [Busser, Brian W.; Singhania, Aditi; Michelson, Alan M.] NHLBI, Lab Dev Syst Biol, Genet & Dev Biol Ctr, Div Intramural Res,NIH, Bethesda, MD 20892 USA. [Jaeger, Savina A.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Bulyk, Martha L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Bulyk, Martha L.] Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA. [Bulyk, Martha L.] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. RP Bulyk, ML (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM mlbulyk@receptor.med.harvard.edu; michelsonam@nhlbi.nih.gov OI Gisselbrecht, Stephen/0000-0001-8723-902X FU National Institutes of Health/National Institutes of General Medical Sciences (NIH/NIGMS) [U01 GM076603]; NIH/National Human Genome Research Institute (NHGRI) [R01 HG005287]; National Heart, Blood and Lung Institute (NHLBI) Division of Intramural Research; NIH [5 T32 GM007748-31]; NIH NRSA [1 F32 GM090645-01A1] FX This work was funded by National Institutes of Health/National Institutes of General Medical Sciences (NIH/NIGMS) [U01 GM076603 to M. L. B.], by NIH/National Human Genome Research Institute (NHGRI) [R01 HG005287 to M. L. B.], by the National Heart, Blood and Lung Institute (NHLBI) Division of Intramural Research (A. M. M.), by a NIH Training Grant [5 T32 GM007748-31 to L. S.], and by a NIH NRSA [1 F32 GM090645-01A1 to L. S.]. Deposited in PMC for immediate release. NR 64 TC 20 Z9 20 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR 15 PY 2012 VL 139 IS 6 BP 1164 EP 1174 DI 10.1242/dev.077362 PG 11 WC Developmental Biology SC Developmental Biology GA 897HY UT WOS:000300640700013 PM 22296846 ER PT J AU Ter-Minassian, M Asomaning, K Zhao, Y Chen, F Su, L Carmella, SG Lin, XH Hecht, SS Christiani, DC AF Ter-Minassian, Monica Asomaning, Kofi Zhao, Yang Chen, Feng Su, Li Carmella, Steven G. Lin, Xihong Hecht, Stephen S. Christiani, David C. TI Genetic variability in the metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE NNK; NNAL; tobacco specific nitrosamine; genetic polymorphism; HSD11B1 ID ALDO-KETO REDUCTASES; LUNG-CANCER; CARBONYL REDUCTION; CARCINOGEN NNK; HUMAN LIVER; CIGARETTE CONSUMPTION; SMOKING-CESSATION; N-NITROSAMINES; DEHYDROGENASE; ASSOCIATION AB Urinary metabolites of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides, termed total NNAL, have recently been shown to be good predictors of lung cancer risk, years before diagnosis. We sought to determine the contribution of several genetic polymorphisms to total NNAL output and inter-individual variability. The study subjects were derived from the Harvard/Massachusetts General Hospital Lung cancer case-control study. We analyzed 87 self-described smokers (35 lung cancer cases and 52 controls), with urine samples collected at time of diagnosis (19921996). We tested 82 tagging SNPs in 16 genes related to the metabolism of NNK to total NNAL. Using weighted case status least squares regression, we tested for the association of each SNP with square-root (sqrt) transformed total NNAL (pmol per mg creatinine), controlling for age, sex, sqrt packyears and sqrt nicotine (ng per mg creatinine). After a sqrt transformation, nicotine significantly predicted a 0.018 (0.014, 0.023) pmol/mg creatinine unit increase in total NNAL for every ng/mg creatinine increase in nicotine at p < 10E-16. Three HSD11B1 SNPs and AKR1C4 rs7083869 were significantly associated with decreasing total NNAL levels: HSD11B1 rs2235543 (p = 4.84E-08) and rs3753519 (p = 0.0017) passed multiple testing adjustment at FDR q = 1.13E-05 and 0.07 respectively, AKR1C4 rs7083869 (p = 0.019) did not, FDR q = 0.51. HSD11B1 and AKR1C4 enzymes are carbonyl reductases directly involved in the single step reduction of NNK to NNAL. The HSD11B1 SNPs may be correlated with the functional variant rs13306401 and the AKR1C4 SNP is correlated with the enzyme activity reducing variant rs17134592, L311V. C1 [Ter-Minassian, Monica] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol EOME Program, Boston, MA 02115 USA. [Carmella, Steven G.; Hecht, Stephen S.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Lin, Xihong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Ter-Minassian, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol EOME Program, 677 Huntington Ave, Boston, MA 02115 USA. EM mtermina@hsph.harvard.edu OI Hecht, Stephen/0000-0001-7228-1356 FU Harvard National Institute for Environmental Health Sciences (NIEHS) Center for Environmental Health [ES00002]; National Institutes of Health Office of Extramural Research (NIH-OER); National Cancer Institute (NCI) [CA074386]; NIH-OER Ruth L. Kirschstein-National Research Service Award [T32 ES 007069] FX Grant sponsor: Harvard National Institute for Environmental Health Sciences (NIEHS) Center for Environmental Health; Grant number: ES00002; Grant sponsors: National Institutes of Health Office of Extramural Research (NIH-OER), National Cancer Institute (NCI), NIH-OER Ruth L. Kirschstein-National Research Service Award; Grant number: T32 ES 007069; Grant sponsor: NCI; Grant number: CA074386 NR 49 TC 10 Z9 10 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 15 PY 2012 VL 130 IS 6 BP 1338 EP 1346 DI 10.1002/ijc.26162 PG 9 WC Oncology SC Oncology GA 878IV UT WOS:000299250700011 PM 21544809 ER PT J AU Bao, Y Nimptsch, K Chan, AT Ng, K Meyerhardt, JA Willett, WC Giovannucci, E Fuchs, CS AF Bao, Ying Nimptsch, Katharina Chan, Andrew T. Ng, Kimmie Meyerhardt, Jeffrey A. Willett, Walter C. Giovannucci, Edward Fuchs, Charles S. TI Reported behavior of eating anything at anytime and risk of colorectal cancer in women SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Eating behavior; colorectal cancer; cohort study ID DISINHIBITION; RESTRAINT AB Although numerous studies have assessed the effect of foods and nutrients on colorectal carcinogenesis, few studies have investigated human eating behavior in relation to risk of colorectal cancer. In our study, we assessed whether the reported behavior of eating anything at anytime influenced colorectal cancer risk and related plasma biomarkers. We prospectively followed up 55,540 women in the Nurses' Health Study who were aged 4873 years, had no history of cancer, ulcerative colitis or diabetes and responded to the item I eat anything I want, anytime I want in the 1994 questionnaire. We also analyzed blood samples for 1,994 women, which were collected in 19891990. During 12 years of follow-up, 552 colorectal cancer cases were documented. After adjusting for age, smoking, body mass index, physical activity, red and processed meat and other known risk factors for colorectal cancer, women who reported eating anything at anytime experienced an increased risk of colorectal cancer (relative risk = 1.28, 95% confidence interval = 1.061.56) compared to those who did not report this behavior. In addition, reporting eating anything at anytime was associated with higher fasting plasma levels of insulin (p = 0.04) and C-peptide (p = 0.05). In conclusion, reports of eating anything at anytime are associated with an increased risk of colorectal cancer in this large prospective cohort study, independent of other potential risk factors for colorectal cancer. C1 [Bao, Ying; Giovannucci, Edward; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Bao, Ying; Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nimptsch, Katharina; Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Ng, Kimmie; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. [Willett, Walter C.; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Bao, Y (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM ying.bao@channing.harvard.edu OI Nimptsch, Katharina/0000-0001-7877-205X FU National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003] FX Grant sponsor: National Institutes of Health; Grant numbers: P01 CA87969, P01 CA55075, P50 CA127003 NR 10 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 15 PY 2012 VL 130 IS 6 BP 1395 EP 1400 DI 10.1002/ijc.26150 PG 6 WC Oncology SC Oncology GA 878IV UT WOS:000299250700017 PM 21520042 ER PT J AU Stirman, SW Kimberly, J Cook, N Calloway, A Castro, F Charns, M AF Stirman, Shannon Wiltsey Kimberly, John Cook, Natasha Calloway, Amber Castro, Frank Charns, Martin TI The sustainability of new programs and innovations: a review of the empirical literature and recommendations for future research SO IMPLEMENTATION SCIENCE LA English DT Review ID HEALTH-PROMOTION INTERVENTIONS; SMOKING-CESSATION COMMIT; 5-YEAR FOLLOW-UP; MENTAL-HEALTH; COMMUNITY INTERVENTION; PREVENTION PROGRAM; BEHAVIORAL INTERVENTIONS; ORGANIZATIONAL CULTURE; MULTISYSTEMIC THERAPY; QUALITY IMPROVEMENT AB Background: The introduction of evidence-based programs and practices into healthcare settings has been the subject of an increasing amount of research in recent years. While a number of studies have examined initial implementation efforts, less research has been conducted to determine what happens beyond that point. There is increasing recognition that the extent to which new programs are sustained is influenced by many different factors and that more needs to be known about just what these factors are and how they interact. To understand the current state of the research literature on sustainability, our team took stock of what is currently known in this area and identified areas in which further research would be particularly helpful. This paper reviews the methods that have been used, the types of outcomes that have been measured and reported, findings from studies that reported long-term implementation outcomes, and factors that have been identified as potential influences on the sustained use of new practices, programs, or interventions. We conclude with recommendations and considerations for future research. Methods: Two coders identified 125 studies on sustainability that met eligibility criteria. An initial coding scheme was developed based on constructs identified in previous literature on implementation. Additional codes were generated deductively. Related constructs among factors were identified by consensus and collapsed under the general categories. Studies that described the extent to which programs or innovations were sustained were also categorized and summarized. Results: Although "sustainability" was the term most commonly used in the literature to refer to what happened after initial implementation, not all the studies that were reviewed actually presented working definitions of the term. Most study designs were retrospective and naturalistic. Approximately half of the studies relied on self-reports to assess sustainability or elements that influence sustainability. Approximately half employed quantitative methodologies, and the remainder employed qualitative or mixed methodologies. Few studies that investigated sustainability outcomes employed rigorous methods of evaluation (e.g., objective evaluation, judgement of implementation quality or fidelity). Among those that did, a small number reported full sustainment or high fidelity. Very little research has examined the extent, nature, or impact of adaptations to the interventions or programs once implemented. Influences on sustainability included organizational context, capacity, processes, and factors related to the new program or practice themselves. Conclusions: Clearer definitions and research that is guided by the conceptual literature on sustainability are critical to the development of the research in the area. Further efforts to characterize the phenomenon and the factors that influence it will enhance the quality of future research. Careful consideration must also be given to interactions among influences at multiple levels, as well as issues such as fidelity, modification, and changes in implementation over time. While prospective and experimental designs are needed, there is also an important role for qualitative research in efforts to understand the phenomenon, refine hypotheses, and develop strategies to promote sustainment. C1 [Stirman, Shannon Wiltsey; Cook, Natasha; Calloway, Amber; Castro, Frank] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Stirman, Shannon Wiltsey; Cook, Natasha; Calloway, Amber; Castro, Frank; Charns, Martin] VA Boston Healthcare Syst, Boston, MA USA. [Stirman, Shannon Wiltsey; Calloway, Amber; Castro, Frank] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Kimberly, John] Univ Penn, Wharton Sch, Dept Healthcare Management, Philadelphia, PA 19104 USA. [Charns, Martin] VA Ctr Org Leadership & Management Res, Boston, MA USA. [Charns, Martin] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Stirman, SW (reprint author), Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. EM Shannon.wiltsey-stirman@va.gov OI Charns, Martin/0000-0002-7102-5331; Wiltsey Stirman, Shannon/0000-0001-9917-5078 FU National Institute of Mental Health [R00 MH 01800, T32 MH 019836, R25 MH080916-01A2]; Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University in St. Louis; Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI) FX The preparation of this article was supported through funding from the National Institute of Mental Health (R00 MH 01800 [Dr. Stirman] and T32 MH 019836 [Dr. Castro; PI: Keane]); through the Implementation Research Institute (IRI), at the George Warren Brown School of Social Work, Washington University in St. Louis, which is funded through an award from the National Institute of Mental Health (R25 MH080916-01A2) and the Department of Veterans Affairs, Health Services Research & Development Service, Quality Enhancement Research Initiative (QUERI). 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, or the Department of Veterans Affairs. Dr. Castro is now affiliated with the VA Maryland Healthcare System NR 208 TC 114 Z9 114 U1 9 U2 89 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD MAR 14 PY 2012 VL 7 AR 17 DI 10.1186/1748-5908-7-17 PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 921LO UT WOS:000302479300001 ER PT J AU Moussaieff, A Yu, J Zhu, H Gattoni-Celli, S Shohami, E Kindy, MS AF Moussaieff, Arieh Yu, Jin Zhu, Hong Gattoni-Celli, Sebastiano Shohami, Esther Kindy, Mark S. TI Protective effects of incensole acetate on cerebral ischemic injury SO BRAIN RESEARCH LA English DT Article DE Cerebral ischemia; Inflammation; NF-kappa B; Neuroprotection; Incensole acetate; Boswellia ID KAPPA-B ACTIVATION; BRAIN-INJURY; IN-VIVO; BEHAVIORAL DEFICITS; DRUG DEVELOPMENT; BOSWELLIC ACIDS; NEUROPROTECTION; STROKE; RECEPTOR; CHANNELS AB The resin of Boswellia species is a major anti-inflammatory agent that has been used for centuries to treat various conditions including injuries and inflammatory conditions. Incensole acetate (IA), a major constituent of this resin, has been shown to inhibit NF-kappa B activation and concomitant inflammation, as well as the neurological deficit following head trauma. Here, we show that IA protects against ischemic neuronal damage and reper-fusion injury in mice, attenuating the inflammatory nature of ischemic damage. IA given post-ischemia, reduced infarct volumes and improved neurological activities in the mouse model of ischemic injury in a dose dependent fashion. The protection from damage was accompanied by inhibition of TNF-alpha, IL-1 beta and TGF-beta expression, as well as NF-kappa B activation following injury. In addition, IA is shown to have a therapeutic window of treatment up to 6 h after ischemic injury. Finally, the protective effects of IA were partially mediated by TRPV3 channels as determined by the TRPV3 deficient mice and channel blocker studies. This study suggests that the anti-inflammatory and neuroprotective activities of IA may serve as a novel therapeutic treatment for ischemic and reperfusion injury, and as a tool in the ongoing research of mechanisms for neurological damage. Published by Elsevier B.V. C1 [Yu, Jin; Zhu, Hong; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29403 USA. [Moussaieff, Arieh] Ariel Univ, Ctr Samaria, Ariel, Israel. [Gattoni-Celli, Sebastiano] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29403 USA. [Gattoni-Celli, Sebastiano; Kindy, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Shohami, Esther] Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, IL-91120 Jerusalem, Israel. [Kindy, Mark S.] Clemson Univ, Dept Bioengn, Clemson, SC USA. RP Kindy, MS (reprint author), Med Univ S Carolina, Dept Neurosci, Strom Thurmond Biomed Res Bldg,Room 503,114 Dough, Charleston, SC 29403 USA. EM kindyms@musc.edu FU National Institutes of Health [ES 016774]; Veterans Administration; National Science Foundation EPSCoR [EPS-0132573, EPS-0447660] FX We thank Aruna Bhat for her technical support and Eileen McFadden for secretarial support. Supported by grants from the National Institutes of Health (ES 016774, MSK), and the Veterans Administration (MSK, SGC) and the National Science Foundation EPSCoR grants (MSK, EPS-0132573 and EPS-0447660). NR 42 TC 11 Z9 12 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 14 PY 2012 VL 1443 BP 89 EP 97 DI 10.1016/j.brainres.2012.01.001 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 920RU UT WOS:000302425800008 PM 22284622 ER PT J AU Kalscheuer, H Danzl, N Onoe, T Faust, T Winchester, R Goland, R Greenberg, E Spitzer, TR Savage, DG Tahara, H Choi, G Yang, YG Sykes, M AF Kalscheuer, Hannes Danzl, Nichole Onoe, Takashi Faust, Ted Winchester, Robert Goland, Robin Greenberg, Ellen Spitzer, Thomas R. Savage, David G. Tahara, Hiroyuki Choi, Goda Yang, Yong-Guang Sykes, Megan TI A Model for Personalized in Vivo Analysis of Human Immune Responsiveness SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID T-CELL RESPONSES; BONE-MARROW-TRANSPLANTATION; HOMEOSTATIC EXPANSION; MULTIPLE-SCLEROSIS; THYMUS GRAFTS; MOUSE MODEL; MICE; TYPE-1; AUTOIMMUNITY; DEFECTS AB Studies of human immune diseases are generally limited to the analysis of peripheral blood lymphocytes of heterogeneous patient populations. Improved models are needed to allow analysis of fundamental immunologic abnormalities predisposing to disease and in which to assess immunotherapies. Immunodeficient mice receiving human fetal thymus grafts and fetal CD34(+) cells intravenously produce robust human immune systems, allowing analysis of human T cell development and function. However, to use humanized mice to study human immune-mediated disorders, immune systems must be generated from adult hematopoietic cells. Here, we demonstrated robust immune reconstitution in mice with hematopoietic stem cells (HSCs) aspirated from bone marrow of adults with type 1 diabetes (T1D) and healthy control volunteers. In these humanized mice, cryopreservation of human leukocyte antigen allele-matched fetal thymic tissue prevented allogeneic adult HSC rejection. Newly generated T cells, which included regulatory T cells (T-regs), were functional and self-tolerant and had a diverse repertoire. The immune recognition of these mice mimicked that of the adult CD34(+) cell donor, but the T cell phenotypes were more predominantly "naive" than those of the adult donors. HSCs from T1D and control donors generated similar numbers of natural T-regs intrathymically; however, peripheral T cells from T1D subjects showed increased proportions of activated or memory cells compared to controls, suggesting possible HSC-intrinsic differences in T cell homeostasis that might underlie immune pathology in T1D. This "personalized immune" mouse provides a new model for individualized analysis of human immune responses that may provide new insights into not only T1D but also other forms of immune function and dysfunction as well. C1 [Kalscheuer, Hannes; Onoe, Takashi; Faust, Ted; Yang, Yong-Guang; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02129 USA. [Kalscheuer, Hannes; Danzl, Nichole; Tahara, Hiroyuki; Choi, Goda; Yang, Yong-Guang; Sykes, Megan] Columbia Univ, Coll Phys & Surg, Dept Med, Columbia Ctr Translat Immunol, New York, NY 10032 USA. [Winchester, Robert] Columbia Univ, Dept Pathol, Coll Phys & Surg, New York, NY 10032 USA. [Goland, Robin; Greenberg, Ellen] Columbia Univ, Coll Phys & Surg, Naomi Berrie Diabet Ctr, New York, NY 10032 USA. [Spitzer, Thomas R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Bone Marrow Transplantat,Dept Med, Boston, MA 02114 USA. [Savage, David G.] Columbia Univ, Coll Phys & Surg, Dept Med, Div Hematol Oncol, New York, NY 10032 USA. [Sykes, Megan] Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY 10032 USA. [Sykes, Megan] Columbia Univ, Coll Phys & Surg, Dept Microbiol Immunol, New York, NY 10032 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02129 USA. EM megan.sykes@columbia.edu FU JDRF Autoimmunity Center at Harvard University; NIH [RO1 AI084903]; Deutsche Forschungsgemeinschaft (German Research Foundation); American Diabetes Association FX Funding: Supported by the JDRF Autoimmunity Center at Harvard University and by NIH grant RO1 AI084903. H. K. was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation) and N.D. was supported by the American Diabetes Association. NR 44 TC 10 Z9 11 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAR 14 PY 2012 VL 4 IS 125 AR 125ra30 DI 10.1126/scitranslmed.3003481 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 909BY UT WOS:000301538300003 PM 22422991 ER PT J AU Zhu, JQ Choi, WS McCoy, JG Negri, A Zhu, JH Naini, S Li, JH Shen, M Huang, WW Bougie, D Rasmussen, M Aster, R Thomas, CJ Filizola, M Springer, TA Coller, BS AF Zhu, Jieqing Choi, Won-Seok McCoy, Joshua G. Negri, Ana Zhu, Jianghai Naini, Sarasija Li, Jihong Shen, Min Huang, Wenwei Bougie, Daniel Rasmussen, Mark Aster, Richard Thomas, Craig J. Filizola, Marta Springer, Timothy A. Coller, Barry S. TI Structure-Guided Design of a High-Affinity Platelet Integrin alpha(IIb)beta(3) Receptor Antagonist That Disrupts Mg2+ Binding to the MIDAS SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID EPTIFIBATIDE-INDUCED THROMBOCYTOPENIA; GLYCOPROTEIN IIB/IIIA ANTAGONISTS; ACUTE MYOCARDIAL-INFARCTION; GPIIB/IIIA ANTAGONISTS; CONFORMATIONAL-CHANGES; FIBRINOGEN BINDING; PRIMARY PCI; IIB-IIIA; RECOGNITION; ACTIVATION AB An integrin found on platelets, alpha(IIb)beta(3) mediates platelet aggregation, and alpha(IIb)beta(3) antagonists are effective antithrombotic agents in the clinic. Ligands bind to integrins in part by coordinating a magnesium ion (Mg2+) located in the beta subunit metal ion-dependent adhesion site (MIDAS). Drugs patterned on the integrin ligand sequence Arg-Gly-Asp have a basic moiety that binds the alpha(IIb) subunit and a carboxyl group that coordinates the MIDAS Mg2+ in the beta(3) subunits. They induce conformational changes in the beta(3) subunit that may have negative consequences such as exposing previously hidden epitopes and inducing the active conformation of the receptor. We recently reported an inhibitor of alpha(IIb)beta(3) (RUC-1) that binds exclusively to the alpha(IIb) subunit; here, we report the structure-based design and synthesis of RUC-2, a RUC-1 derivative with a similar to 100-fold higher affinity. RUC-2 does not induce major conformational changes in beta(3) as judged by monoclonal antibody binding, light scattering, gel chromatography, electron microscopy, and a receptor priming assay. X-ray crystallography of the RUC-2-alpha(IIb)beta(3) headpiece complex in 1 mM calcium ion (Ca2+)/5 mM Mg2+ at 2.6 angstrom revealed that RUC-2 binds to aIIb the way RUC-1 does, but in addition, it binds to the beta(3) MIDAS residue glutamic acid 220, thus displacing Mg2+ from the MIDAS. When the Mg2+ concentration was increased to 20 mM, however, Mg2+ was identified in the MIDAS and RUC-2 was absent. RUC-2's ability to inhibit ligand binding and platelet aggregation was diminished by increasing the Mg2+ concentration. Thus, RUC-2 inhibits ligand binding by a mechanism different from that of all other alpha(IIb)beta(3) antagonists and may offer advantages as a therapeutic agent. C1 [Choi, Won-Seok; Naini, Sarasija; Li, Jihong; Coller, Barry S.] Rockefeller Univ, Lab Blood & Vasc Biol, New York, NY 10065 USA. [Zhu, Jieqing; Zhu, Jianghai; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Zhu, Jieqing; Zhu, Jianghai; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Zhu, Jieqing; Bougie, Daniel; Rasmussen, Mark; Aster, Richard] Med Coll Wisconsin, BloodCtr Wisconsin, Milwaukee, WI 53201 USA. [McCoy, Joshua G.; Shen, Min; Huang, Wenwei; Thomas, Craig J.] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Negri, Ana; Filizola, Marta] Mt Sinai Sch Med, Dept Struct & Chem Biol, New York, NY 10029 USA. RP Coller, BS (reprint author), Rockefeller Univ, Lab Blood & Vasc Biol, New York, NY 10065 USA. EM collerb@rockefeller.edu FU National Heart, Lung, and Blood Institute [HL19278, HL13629, HL48675]; National Center for Research Resources, NIH [ULRR024143]; Molecular Libraries Initiative of the NIH Roadmap for Medical Research; National Human Genome Research Institute; Stony Brook University; National Research Foundation of Korea; Korean Government [NRF-2009-352-E00042]; NSF by Texas Advanced Computing Center [TG-MCB080109N] FX Funding: Supported, in part, by grants HL19278, HL13629, and HL48675 from the National Heart, Lung, and Blood Institute; Clinical and Translational Science Award grant ULRR024143 from the National Center for Research Resources, NIH; the Molecular Libraries Initiative of the NIH Roadmap for Medical Research and the Intramural Research Program of the National Human Genome Research Institute; funds from Stony Brook University; and the National Research Foundation of Korea Grant funded by the Korean Government (NRF-2009-352-E00042). The computations were supported in part by the NSF through TeraGrid advanced computing resources provided by Texas Advanced Computing Center under grant TG-MCB080109N (principal investigator: M.F.). NR 54 TC 11 Z9 11 U1 1 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAR 14 PY 2012 VL 4 IS 125 AR 125ra32 DI 10.1126/scitranslmed.3003576 PG 13 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 909BY UT WOS:000301538300007 PM 22422993 ER PT J AU Joynt, KE Jha, AK AF Joynt, Karen E. Jha, Ashish K. TI The Relationship Between Cost and Quality No Free Lunch SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID REGIONAL-VARIATIONS; CARE; HOSPITALS; OUTCOMES C1 [Joynt, Karen E.; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Joynt, Karen E.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu NR 8 TC 14 Z9 15 U1 1 U2 11 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 MAR 14 PY 2012 VL 307 IS 10 BP 1082 EP 1083 DI 10.1001/jama.2012.287 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 908GU UT WOS:000301479700030 PM 22416105 ER PT J AU Azad, A Pyne, S Pothen, A AF Azad, Ariful Pyne, Saumyadipta Pothen, Alex TI Matching phosphorylation response patterns of antigen-receptor-stimulated T cells via flow cytometry SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 1st Annual Meeting of the Great Lakes Bioinformatics (GLBIO) CY MAY 02-04, 2011 CL Ohio Univ, Athens, OH HO Ohio Univ ID MEMORY; EFFECTERS; MIXTURE; NAIVE AB Background: When flow cytometric data on mixtures of cell populations are collected from samples under different experimental conditions, computational methods are needed (a) to classify the samples into similar groups, and (b) to characterize the changes within the corresponding populations due to the different conditions. Manual inspection has been used in the past to study such changes, but high-dimensional experiments necessitate developing new computational approaches to this problem. A robust solution to this problem is to construct distinct templates to summarize all samples from a class, and then to compare these templates to study the changes across classes or conditions. Results: We designed a hierarchical algorithm, flowMatch, to first match the corresponding clusters across samples for producing robust meta-clusters, and to then construct a high-dimensional template as a collection of meta-clusters for each class of samples. We applied the algorithm on flow cytometry data obtained from human blood cells before and after stimulation with anti-CD3 monoclonal antibody, which is reported to change phosphorylation responses of memory and naive T cells. The flowMatch algorithm is able to construct representative templates from the samples before and after stimulation, and to match corresponding meta-clusters across templates. The templates of the pre-stimulation and post-stimulation data corresponding to memory and naive T cell populations clearly show, at the level of the meta-clusters, the overall phosphorylation shift due to the stimulation. Conclusions: We concisely represent each class of samples by a template consisting of a collection of meta-clusters (representative abstract populations). Using flowMatch, the meta-clusters across samples can be matched to assess overall differences among the samples of various phenotypes or time-points. C1 [Pyne, Saumyadipta] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Azad, Ariful; Pothen, Alex] Purdue Univ, Dept Comp Sci, W Lafayette, IN 47906 USA. [Pyne, Saumyadipta] MIT, Broad Inst, Cambridge, MA 02142 USA. [Pyne, Saumyadipta] Harvard Univ, Cambridge, MA 02142 USA. RP Pyne, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM spyne@broad.mit.edu; apothen@purdue.edu NR 15 TC 7 Z9 7 U1 2 U2 4 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 MAR 13 PY 2012 VL 13 SU 2 AR S10 DI 10.1186/1471-2105-13-S2-S10 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 941BE UT WOS:000303936000011 PM 22536861 ER PT J AU Haines, M Brown, B Craig, J D'Este, C Elliott, E Klineberg, E McInnes, E Middleton, S Paul, C Redman, S Yano, EM AF Haines, Mary Brown, Bernadette Craig, Jonathan D'Este, Catherine Elliott, Elizabeth Klineberg, Emily McInnes, Elizabeth Middleton, Sandy Paul, Christine Redman, Sally Yano, Elizabeth M. CA Clin Networks Res Grp TI Determinants of successful clinical networks: the conceptual framework and study protocol SO IMPLEMENTATION SCIENCE LA English DT Article ID HEALTH-CARE; QUALITY; CANCER; IMPLEMENTATION; IMPROVEMENT; GUIDELINES; PROGRAM; IMPACT; MODEL AB Background: Clinical networks are increasingly being viewed as an important strategy for increasing evidence-based practice and improving models of care, but success is variable and characteristics of networks with high impact are uncertain. This study takes advantage of the variability in the functioning and outcomes of networks supported by the Australian New South Wales (NSW) Agency for Clinical Innovation's non-mandatory model of clinical networks to investigate the factors that contribute to the success of clinical networks. Methods/Design: The objective of this retrospective study is to examine the association between external support, organisational and program factors, and indicators of success among 19 clinical networks over a three-year period (2006-2008). The outcomes (health impact, system impact, programs implemented, engagement, user perception, and financial leverage) and explanatory factors will be collected using a web-based survey, interviews, and record review. An independent expert panel will provide judgements about the impact or extent of each network's initiatives on health and system impacts. The ratings of the expert panel will be the outcome used in multivariable analyses. Following the rating of network success, a qualitative study will be conducted to provide a more in-depth examination of the most successful networks. Discussion: This is the first study to combine quantitative and qualitative methods to examine the factors that contribute to the success of clinical networks and, more generally, is the largest study of clinical networks undertaken. The adaptation of expert panel methods to rate the impacts of networks is the methodological innovation of this study. The proposed project will identify the conditions that should be established or encouraged by agencies developing clinical networks and will be of immediate use in forming strategies and programs to maximise the effectiveness of such networks. C1 [Haines, Mary; Brown, Bernadette; Redman, Sally] Sax Inst, Haymarket, Australia. [Haines, Mary; Craig, Jonathan] Univ Sydney, Sch Publ Hlth, Camperdown, NSW, Australia. [D'Este, Catherine] Univ Newcastle, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia. [Elliott, Elizabeth; Klineberg, Emily] Univ Sydney, Sch Clin, Childrens Hosp Westmead, Westmead, NSW 2145, Australia. [McInnes, Elizabeth; Middleton, Sandy] Australian Catholic Univ, Natl Ctr Clin Outcomes Res NaCCOR, Darlinghurst, NSW, Australia. [McInnes, Elizabeth; Middleton, Sandy] Nursing Res Inst St Vincents & Mater Hlth Sydney, Darlinghurst, NSW, Australia. [Paul, Christine] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia. [Yano, Elizabeth M.] VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. RP Haines, M (reprint author), Sax Inst, Haymarket, Australia. EM mary.haines@saxinstitute.org.au RI D'ESTE, CATHERINE/G-7392-2013; Craig, Jonathan/E-2813-2013; Scott, Anthony/E-6636-2010; OI Craig, Jonathan/0000-0002-2548-4035; McInnes, Liz/0000-0002-0567-9679; Scott, Anthony/0000-0002-2851-5378; Middleton, Sandy/0000-0002-7201-4394 FU National Health and Medical Research Council of Australia [571447]; NSW Agency for Clinical Innovation as part of the National Health and Medical Research Council of Australia's (NHMRC) FX This research is supported by the National Health and Medical Research Council of Australia through their partnership project grant scheme (ID: 571447). This protocol has been approved by the University of Sydney, Human Research Ethics Committee in August 2011 (ID: 13988).; Hunter Watt and Kate Needham, who are part of the 'Clinical Networks Research Group', are employed by the NSW Agency for Clinical Innovation. This Agency has provided funds to support this research as part of the National Health and Medical Research Council of Australia's (NHMRC) partnership project grant scheme. These funds have been awarded on the basis of a NHMRC deed of agreement governing the governance and conduct of research in Australia. The other authors declare that they have no competing interests. NR 42 TC 10 Z9 10 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD MAR 13 PY 2012 VL 7 AR 16 DI 10.1186/1748-5908-7-16 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 930PK UT WOS:000303151400001 PM 22414246 ER PT J AU Levison, JH Orrell, C Gallien, S Kuritzkes, DR Fu, N Losina, E Freedberg, KA Wood, R AF Levison, Julie H. Orrell, Catherine Gallien, Sebastien Kuritzkes, Daniel R. Fu, Naishin Losina, Elena Freedberg, Kenneth A. Wood, Robin TI Virologic Failure of Protease Inhibitor-Based Second-Line Antiretroviral Therapy without Resistance in a Large HIV Treatment Program in South Africa SO PLOS ONE LA English DT Article ID TREATMENT-NAIVE PATIENTS; DRUG-RESISTANCE; REVERSE-TRANSCRIPTASE; LOPINAVIR-RITONAVIR; EARLY MORTALITY; PATIENTS LOST; FOLLOW-UP; CLADE-C; OUTCOMES; MUTATIONS AB Background: We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa. Methodology/ Principal Findings: HIV-infected patients >= 15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged. Conclusions/ Significance: Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure. C1 [Levison, Julie H.; Fu, Naishin; Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Levison, Julie H.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Orrell, Catherine; Wood, Robin] Univ Cape Town, Dept Med, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Levison, Julie H.; Gallien, Sebastien; Kuritzkes, Daniel R.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Gallien, Sebastien; Kuritzkes, Daniel R.; Losina, Elena; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. RP Levison, JH (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM jlevison@partners.org RI Gallien, Sebastien/F-9930-2015; OI Gallien, Sebastien/0000-0002-8033-0936; Orrell, Catherine/0000-0003-1134-7475 FU United States National Institute of Allergy and Infectious Diseases [NIAID T32 AI007433, R01AI058736, K24 A1062476]; National Center for Research Resources [K24 RR016482]; Harvard University Center for AIDS Research [P30-AI060354]; Virology Specialty Laboratory from AIDS Clinical Trials Group [U01 AI068636]; "Agence Nationale de Recherche sur le SIDA" (French National Agency for Research on AIDS), France; Abbott; Boehringer Ingelheim; Gilead; GlaxoSmithKline; Merck; ViiV FX This project was supported by the United States National Institute of Allergy and Infectious Diseases (NIAID T32 AI007433, R01AI058736, K24 A1062476), the National Center for Research Resources (K24 RR016482), Harvard University Center for AIDS Research (P30-AI060354), Virology Specialty Laboratory subcontract from the AIDS Clinical Trials Group (U01 AI068636). SG was a recipient of the "Agence Nationale de Recherche sur le SIDA" (French National Agency for Research on AIDS) Fellowship Grant for Post-Graduate Studies, France. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The authors have read the journal's policy and have the following competing interest: DRK is a consultant to and has received honoraria or research support from Abbott, Boehringer Ingelheim, Gilead, GlaxoSmithKline, Merck and ViiV. This does not alter the authors' adherence to all the PloS ONE policies on sharing data and materials. All other authors have declared that no competing interests exist. NR 40 TC 21 Z9 21 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 13 PY 2012 VL 7 IS 3 AR e32144 DI 10.1371/journal.pone.0032144 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 930IA UT WOS:000303129700006 PM 22427821 ER PT J AU Liu, EB Wadford, DA Seto, J Vu, M Hudson, NR Thrasher, L Torres, S Dyer, DW Chodosh, J Seto, D Jones, MS AF Liu, Elizabeth B. Wadford, Debra A. Seto, Jason Vu, Maria Hudson, Nolan Ryan Thrasher, Lisa Torres, Sarah Dyer, David W. Chodosh, James Seto, Donald Jones, Morris S. TI Computational and Serologic Analysis of Novel and Known Viruses in Species Human Adenovirus D in Which Serology and Genomics Do Not Correlate SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; EPIDEMIC KERATOCONJUNCTIVITIS; MOLECULAR EVOLUTION; PROVIDES EVIDENCE; RECOMBINATION; IDENTIFICATION; INFECTION; STRAINS; TYPE-15; SYSTEM AB In November of 2007 a human adenovirus (HAdV) was isolated from a bronchoalveolar lavage (BAL) sample recovered from a biopsy of an AIDS patient who presented with fever, cough, tachycardia, and expiratory wheezes. To better understand the isolated virus, the genome was sequenced and analyzed using bioinformatic and phylogenomic analysis. The results suggest that this novel virus, which is provisionally named HAdV-D59, may have been created from multiple recombination events. Specifically, the penton, hexon, and fiber genes have high nucleotide identity to HAdV-D19C, HAdV-D25, and HAdV-D56, respectively. Serological results demonstrated that HAdV-D59 has a neutralization profile that is similar yet not identical to that of HAdV-D25. Furthermore, we observed a two-fold difference between the ability of HAdV-D15 and HAdV-D25 to be neutralized by reciprocal antiserum indicating that the two hexon proteins may be more similar in epitopic conformation than previously assumed. In contrast, hexon loops 1 and 2 of HAdV-D15 and HAdV-D25 share 79.13 and 92.56 percent nucleotide identity, respectively. These data suggest that serology and genomics do not always correlate. C1 [Liu, Elizabeth B.; Seto, Jason; Seto, Donald; Jones, Morris S.] George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA. [Wadford, Debra A.; Vu, Maria] Calif Dept Publ Hlth, Viral & Rickettsial Dis Lab, Richmond, CA USA. [Hudson, Nolan Ryan; Thrasher, Lisa; Torres, Sarah] Travis AFB, David Grant USAF Med Ctr, Fairfield, CA USA. [Dyer, David W.] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA. [Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab, Boston, MA USA. RP Jones, MS (reprint author), George Mason Univ, Sch Syst Biol, Manassas, VA 20110 USA. EM drmorrisj@yahoo.com FU United States Air Force Surgeon General [FDG20040024E]; Research to Prevent Blindness, Inc.; [R01EY013124]; [P30EY014104] FX This research was financially supported by grant R01EY013124 (DWD, DS, MSJ and JC) and P30EY014104 (JC). LS, NRH, and MSJ were supported by United States Air Force Surgeon General grant FDG20040024E. JC is also funded by an unrestricted grant to the Department of Ophthalmology, Harvard Medical School, from Research to Prevent Blindness, Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 14 Z9 17 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 13 PY 2012 VL 7 IS 3 AR e33212 DI 10.1371/journal.pone.0033212 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 930IA UT WOS:000303129700038 PM 22427992 ER PT J AU Panagia, M Winston, B Click, JW Sabatine, MS Resnic, FS AF Panagia, Marcello Winston, Brion Click, James W. Sabatine, Marc S. Resnic, Frederic S. TI A Rare Complication of Infective Endocarditis SO CIRCULATION LA English DT Editorial Material ID CORONARY-ARTERY; ANEURYSM C1 [Panagia, Marcello] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02144 USA. [Click, James W.] Brigham & Womens Hosp, Dept Med, Div Internal Med, Boston, MA 02115 USA. [Winston, Brion; Sabatine, Marc S.; Resnic, Frederic S.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Dis, Boston, MA 02115 USA. RP Panagia, M (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, 55 Fruit St,YAW 5700, Boston, MA 02144 USA. EM mpanagia@partners.org NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 13 PY 2012 VL 125 IS 10 BP 1316 EP 1317 DI 10.1161/CIRCULATIONAHA.110.982702 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 914GM UT WOS:000301937500025 PM 22412092 ER PT J AU Shivdasani, RA AF Shivdasani, Ramesh A. TI GEFs on the RhoAd to a Colossal Nucleus SO DEVELOPMENTAL CELL LA English DT Editorial Material ID MEGAKARYOCYTES; POLYPLOIDY AB Cytokinesis in normal cell division requires RhoA-regulated actomyosin contraction of the cleavage furrow; this process is aborted in megakaryocyte endomitosis, leading to polyploidy. In this issue of Developmental Cell, Gao et al. (2012) trace the basis of endomitosis to sequential downregulation of guanine nucleotide exchange factors GEF-H1 and ECT2. C1 [Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA. [Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Shivdasani, RA (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02215 USA. EM ramesh_shivdasani@dfci.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAR 13 PY 2012 VL 22 IS 3 BP 471 EP 472 DI 10.1016/j.devcel.2012.02.010 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 911FB UT WOS:000301701600002 PM 22421037 ER PT J AU Xu, C Fan, ZP Muller, P Fogley, R DiBiase, A Trompouki, E Unternaehrer, J Xiong, FZ Torregroza, I Evans, T Megason, SG Daley, GQ Schier, AF Young, RA Zon, LI AF Xu, Cong Fan, Zi Peng Mueller, Patrick Fogley, Rachel DiBiase, Anthony Trompouki, Eirini Unternaehrer, Juli Xiong, Fengzhu Torregroza, Ingrid Evans, Todd Megason, Sean G. Daley, George Q. Schier, Alexander F. Young, Richard A. Zon, Leonard I. TI Nanog-like Regulates Endoderm Formation through the Mxbc2-Nodal Pathway SO DEVELOPMENTAL CELL LA English DT Article ID EMBRYONIC STEM-CELLS; YOLK SYNCYTIAL LAYER; ONE-EYED PINHEAD; PRIMITIVE ENDODERM; ZEBRAFISH BLASTOMERES; GROUND-STATE; PROTEIN; PLURIPOTENCY; MESODERM; GENE AB In mammalian embryonic stem cells, the acquisition of pluripotency is dependent on Nanog, but the in vivo analysis of Nanog has been hampered by its requirement for early mouse development. In an effort to examine the role of Nanog in vivo, we identified a zebrafish Nanog ortholog and found that its knockdown impaired endoderm formation. Genome-wide transcription analysis revealed that nanog-like morphants fail to develop the extraembryonic yolk syncytial layer (YSL), which produces Nodal, required for endoderm induction. We examined the genes that were regulated by Nanog-like and identified the homeobox gene mxtx2, which is both necessary and sufficient for YSL induction. Chromatin immunoprecipitation assays and genetic studies indicated that Nanog-like directly activates mxtx2, which, in turn, specifies the YSL lineage by directly activating YSL genes. Our study identifies a Nanog-like-Mxtx2-Nodal pathway and establishes a role for Nanog-like in regulating the formation of the extraembryonic tissue required for endoderm induction. C1 [Xu, Cong; Fogley, Rachel; DiBiase, Anthony; Trompouki, Eirini; Unternaehrer, Juli; Daley, George Q.; Zon, Leonard I.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Xu, Cong; DiBiase, Anthony; Trompouki, Eirini; Unternaehrer, Juli; Daley, George Q.; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Xu, Cong; DiBiase, Anthony; Trompouki, Eirini; Unternaehrer, Juli; Daley, George Q.; Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. [Fan, Zi Peng; Young, Richard A.] MIT, Whitehead Inst, Cambridge, MA 02142 USA. [Fan, Zi Peng; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Mueller, Patrick; Schier, Alexander F.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Xiong, Fengzhu; Megason, Sean G.] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA. [Torregroza, Ingrid; Evans, Todd] Cornell Univ, Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA. RP Zon, LI (reprint author), Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu RI Young, Richard/F-6495-2012; Muller, Patrick/C-8096-2014; XIONG, FENGZHU/A-9590-2015 OI Young, Richard/0000-0001-8855-8647; Muller, Patrick/0000-0002-0702-6209; XIONG, FENGZHU/0000-0002-6153-0254 FU National Institutes of Health [5R01HL048801-18, 5U01HL10001-02, R01 HG002668, HL056182] FX This work was supported by National Institutes of Health grants 5R01HL048801-18 and 5U01HL10001-02 (L.I.Z.), R01 HG002668 (R.A.Y.), and HL056182 (T.E.). We thank I. Swinburne, J. Mullor, and R. Zhao for providing reagents; Y. Zhou, A. Chen, and L. Lawson for technical assistance; and O. Tamplin for critical appraisal of the work. L.I.Z. and G.Q.D. are Howard Hughes Medical Institute investigators. L.I.Z. is a founder and stockholder of Fate, Inc., and a scientific advisor for Stemgent. NR 57 TC 33 Z9 34 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAR 13 PY 2012 VL 22 IS 3 BP 625 EP 638 DI 10.1016/j.devcel.2012.01.003 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 911FB UT WOS:000301701600016 PM 22421047 ER PT J AU Martins, Y Lederman, RI Lowenstein, CL Joffe, S Neville, BA Hastings, BT Abel, GA AF Martins, Y. Lederman, R. I. Lowenstein, C. L. Joffe, S. Neville, B. A. Hastings, B. T. Abel, G. A. TI Increasing response rates from physicians in oncology research: a structured literature review and data from a recent physician survey SO BRITISH JOURNAL OF CANCER LA English DT Review DE surveys; response rates; health services research; oncology ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PHYSICIANS; FOLLOW-UP CARE; MAIL SURVEY; POSTAL SURVEY; GENERAL-PRACTITIONERS; ORTHOPEDIC SURGEONS; MONETARY INCENTIVES; COST-EFFECTIVENESS; CANCER SURVIVORS AB Although the physician survey has become an important tool for oncology-focused health services research, such surveys often achieve low response rates. This mini-review reports the results of a structured review of the literature relating to increasing response rates for physician surveys, as well as our own experience from a survey of physicians as to their referral practices for suspected haematologic malignancy in the United States. PubMed and PsychINFO databases were used to identify methodological articles assessing factors that influence response rates for physician surveys; the results were tabulated and reviewed for trends. We also analysed the impact of a follow-up telephone call by a physician investigator to initial non-responders in our own mailed physician survey, comparing the characteristics of those who responded before vs after the call. The systematic review suggested that monetary incentives and paper (vs web or email) surveys increase response rates. In our own survey, follow-up telephone calls increased the response rate from 43.7% to 70.5%, with little discernible difference in the characteristics of early vs later responders. We conclude that in addition to monetary incentives and paper surveys, physician-to-physician follow-up telephone calls are an effective method to increase response rates in oncology-focused physician surveys. British Journal of Cancer (2012) 106, 1021-1026. doi:10.1038/bjc.2012.28 www.bjcancer.com Published online 28 February 2012 (C) 2012 Cancer Research UK C1 [Martins, Y.; Lederman, R. I.; Lowenstein, C. L.; Joffe, S.; Hastings, B. T.; Abel, G. A.] Dana Farber Canc Inst, Ctr Populat Sci, Boston, MA 02215 USA. [Martins, Y.; Joffe, S.] Childrens Hosp, Dept Med, Boston, MA 02215 USA. [Joffe, S.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Neville, B. A.; Hastings, B. T.; Abel, G. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Abel, GA (reprint author), Dana Farber Canc Inst, Ctr Populat Sci, Boston, MA 02215 USA. EM gregory_abel@dfci.harvard.edu OI Martins, Yolanda/0000-0002-3983-3531; Joffe, Steven/0000-0002-0667-7384 FU Division of Cancer Prevention and Control of the Centers for Disease Control and Prevention (CDC) in Atlanta GA FX This work was partially supported by a contract from the Division of Cancer Prevention and Control of the Centers for Disease Control and Prevention (CDC) in Atlanta GA. The findings and conclusions do not necessarily represent the CDC's views. NR 58 TC 31 Z9 31 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 13 PY 2012 VL 106 IS 6 BP 1021 EP 1026 DI 10.1038/bjc.2012.28 PG 6 WC Oncology SC Oncology GA 909DA UT WOS:000301541200001 PM 22374464 ER PT J AU Chang, JJ Lacas, A Lindsay, RJ Doyle, EH Axten, KL Pereyra, F Rosenberg, ES Walker, BD Allen, TM Altfeld, M AF Chang, J. Judy Lacas, Aurore Lindsay, Robert J. Doyle, Erin H. Axten, Karen L. Pereyra, Florencia Rosenberg, Eric S. Walker, Bruce D. Allen, Todd M. Altfeld, Marcus TI Differential regulation of toll-like receptor pathways in acute and chronic HIV-1 infection SO AIDS LA English DT Article DE dendritic cells; HIV-1; innate immunity; monocytes; pathogenesis; toll-like receptor ID PLASMACYTOID DENDRITIC CELLS; ACTIVE ANTIRETROVIRAL THERAPY; ALPHA-INTERFERON PRODUCTION; PRODUCE IFN-ALPHA; I INTERFERON; HIV-1-INFECTED PATIENTS; IMMUNE ACTIVATION; VIRUS-INFECTIONS; BLOOD; INDIVIDUALS AB Objective and design: The objective of this study was to determine changes in toll-like receptor (TLR) responses of monocytes, myeloid dendritic cells and plasmacytoid dendritic cells during primary and chronic HIV-1 infection. TLRs serve as important innate receptors to sense pathogens, and have been implicated in mediating immune activation in HIV-1 infection. Studies assessing the consequences of HIV-1 infection on the ability of innate immune cells to respond to TLR stimulation have come to varying conclusions. Methods: Using intracellular flow cytometry, cytokine production by cryopreserved peripheral blood mononuclear cells from healthy controls and HIV-1-infected individuals were examined after TLR stimulation. Results: We observed that the effect of HIV-1 infection on TLR responses not only depended on the stage of HIV-1 infection, but was also dependent on the individual receptor and cell type examined. Monocyte and myeloid dendritic cell responses to TLR8 stimulation were associated with HIV-1 viral load and CD4(+) T-cell count, whereas plasmacytoid dendritic cell responses to TLR7 stimulation were not. Responses to TLR2 stimulation were not affected by HIV-1 infection, whereas responses to TLR9 stimulation were universally decreased in all HIV-1-infected individuals examined regardless of treatment or clinical parameters. Conclusion: Responsiveness to TLR7/8 stimulation, which have been shown to recognize HIV-1 ssRNA, did not decrease in chronic infection, and may represent a contributing factor to ongoing T-cell immune activation in the setting of chronic viremic HIV-1 infection. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Chang, J. Judy; Lacas, Aurore; Lindsay, Robert J.; Doyle, Erin H.; Axten, Karen L.; Pereyra, Florencia; Walker, Bruce D.; Allen, Todd M.; Altfeld, Marcus] Harvard Univ, Sch Med, Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA USA. [Rosenberg, Eric S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Bldg 149,13th St,6th Floor, Navy Yard, MA 02129 USA. EM maltfeld@partners.org RI Ghartouchent, malek/B-9088-2012; Allen, Todd/F-5473-2011; OI Doyle, Erin/0000-0001-9380-2819 FU NIH/NIAID [R21 AI071806, R01 AI078784, P01 AI074415]; National Health and Medical Research Council of Australia [519578]; Phillip T. and Susan M. Ragon Foundation; Bill & Melinda Gates Foundation FX These studies were supported by NIH/NIAID grants R21 AI071806, R01 AI078784 and P01 AI074415 (MA); a fellowship awarded from the National Health and Medical Research Council of Australia (519578) and Ragon Fellowship by the Phillip T. and Susan M. Ragon Foundation to JJC, and the Bill & Melinda Gates Foundation. NR 43 TC 31 Z9 33 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 13 PY 2012 VL 26 IS 5 BP 533 EP 541 DI 10.1097/QAD.0b013e32834f3167 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 906GN UT WOS:000301333000002 PM 22210629 ER PT J AU Li, N Spiegelman, D Drain, P Mwiru, RS Mugusi, F Chalamilla, G Fawzi, WW AF Li, Nan Spiegelman, Donna Drain, Paul Mwiru, Ramadhani S. Mugusi, Ferdinand Chalamilla, Guerino Fawzi, Wafaie W. TI Predictors of weight loss after HAART initiation among HIV-infected adults in Tanzania SO AIDS LA English DT Article DE Africa; HAART; HIV/AIDS; weight loss ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; RESTING ENERGY-EXPENDITURE; MULTICENTER AIDS COHORT; WASTING SYNDROME; DISEASE PROGRESSION; NUTRITIONAL-STATUS; ERA; MORTALITY; SURVIVAL AB Objective: To explore the predictors of weight loss after highly active antiretroviral therapy (HAART) initiation in a large cohort of HIV-infected adults living in Dar es Salaam, Tanzania. Design: Cross-sectional and longitudinal analysis of a cohort of HIV-infected adults on HAART. Methods: HIV-infected adults (n = 18 965) were enrolled between November 2004 to December 2009 in Dar es Salaam, Tanzania. Log-binomial regression and Cox proportional hazard regression were used to explore the predictors of short-term (3 months) and long-term significant weight loss (>= 5%) after HAART initiation. Results: At 3 months after HAART initiation, 8% patients lost greater than or equal to 5% weight. Underweight patients at initiation gained more weight than other body mass index (BMI) groups. Younger or older than age group 30-39, lower socioeconomic status (SES), higher BMI, lower hemoglobin, difficulty breathing, loss of appetite, nausea/vomiting at baseline were associated with the risk of significant weight loss at 3 months after initiation. During a median follow-up period of 10 months [interquartile range (IQR) 4-20 months], 31% patients had experienced an initial significant weight loss after HAART initiation. In addition to time-varying CD4 cell count and hemoglobin level, age, sex, baseline BMI and having loss of appetite, and nausea/vomiting at baseline were associated with the risk of long-term significant weight loss. Conclusion: Our study suggested that a significant percentage of patients continue to lose weight after HAART initiation. Our findings on the effect of socio-demographics, symptoms and diseases, biomedical indicators in relation to weight loss provide important information that has significant practical implications. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Li, Nan; Mwiru, Ramadhani S.; Fawzi, Wafaie W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02120 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02120 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02120 USA. [Drain, Paul] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Drain, Paul] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Mugusi, Ferdinand] Muhimbili Univ Hlth & Allied Sci, Dept Internal Med, Dar Es Salaam, Tanzania. [Chalamilla, Guerino] MDH, Dar Es Salaam, Tanzania. [Fawzi, Wafaie W.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02120 USA. RP Li, N (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 1633 Tremont St, Boston, MA 02120 USA. EM nli@hsph.harvard.edu OI Drain, Paul/0000-0003-3300-3817 FU US President's Emergency Plan for AIDS Relief (PEPFAR) FX This study is supported by US President's Emergency Plan for AIDS Relief (PEPFAR). NR 43 TC 3 Z9 3 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 13 PY 2012 VL 26 IS 5 BP 577 EP 585 DI 10.1097/QAD.0b013e32834f9851 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 906GN UT WOS:000301333000007 PM 22156968 ER PT J AU Fitch, K Abbara, S Lee, H Stavrou, E Sacks, R Michel, T Hemphill, L Torriani, M Grinspoon, S AF Fitch, Kathleen Abbara, Suhny Lee, Hang Stavrou, Eleni Sacks, Rachel Michel, Theresa Hemphill, Linda Torriani, Martin Grinspoon, Steven TI Effects of lifestyle modification and metformin on atherosclerotic indices among HIV-infected patients with the metabolic syndrome SO AIDS LA English DT Article DE atherosclerosis; HIV; lifestyle modification; metformin ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; INTRAMYOCELLULAR LIPID-ACCUMULATION; IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; ACUTE MYOCARDIAL-INFARCTION; INTIMA-MEDIA THICKNESS; RISK-FACTORS; INSULIN SENSITIVITY AB Objective: Metabolic abnormalities including diabetes, dyslipidemia, hypertension, and abdominal obesity occur commonly in HIV patients, are associated with increased coronary artery calcification (CAC), and contribute to increased cardiovascular disease (CVD) in this population. We hypothesized that lifestyle modification (LSM) and metformin would improve CVD indices in HIV patients with metabolic syndrome. Design: A randomized, placebo-controlled trial to investigate LSM and metformin, alone and in combination, over 1 year, among 50 HIV-infected patients with metabolic syndrome. Methods: We assessed CAC, cardiovascular and metabolic indices. Results: Among the participants, duration of HIV-infection was 14 +/- 1 year and duration of antiretroviral therapy was 6 +/- 1 year. Metformin-treated patients demonstrated significantly less progression of CAC (-1 +/- 2 vs. 33 +/- 17, P = 0.004, metformin vs. placebo), whereas the effect of LSM on CAC progression was not significant (8 +/- 6 vs. 21 +/- 14, P = 0.82, LSM vs. no-LSM). Metformin had a significantly greater effect on CAC than LSM (P = 0.01). Metformin-treated patients also demonstrated less progression in calcified plaque volume (-0.4 +/- 1.9 vs. 27.6 +/- 13.8 mu l, P = 0.008) and improved homeostatic model of assessment-insulin resistance (HOMA-IR) (P = 0.05) compared with placebo. Participants randomized to LSM vs. no-LSM showed significant improvement in HDL (P = 0.03), high-sensitivity C-reactive protein (hsCRP) (P = 0.05), and cardiorespiratory fitness. Changes in CAC among the four groups - no-LSM-placebo (43 +/- 30); LSM-placebo (19 +/- 7); no-LSM-metformin (1 +/- 1) and LSM-metformin (-4 +/- 6) - were different (P 0.03 for ANOVA and linear trend across groups), and the majority of this effect was mediated by metformin. Results are mean +/- SEM. Conclusion: Metformin prevents plaque progression in HIV-infected patients with the metabolic syndrome. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Fitch, Kathleen; Stavrou, Eleni; Sacks, Rachel; Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Abbara, Suhny] Massachusetts Gen Hosp, Cardiovasc Imaging Sect, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Michel, Theresa] Massachusetts Gen Hosp, Dept Phys Therapy, Boston, MA 02114 USA. [Hemphill, Linda] Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA. [Torriani, Martin] Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, LON5-207,55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org RI Ghartouchent, malek/B-9088-2012 FU NIH [R01 DK49302, M01-RR-01066, 1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center; National Center for Research Resources; Theratechnologies; Bristol Meyers Squibb FX Funding was provided by NIH R01 DK49302 and by NIH M01-RR-01066 and 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center, from the National Center for Research Resources.; There are no conflicts of interest related to this work. S.G. has received research funding from Theratechnologies and Bristol Meyers Squibb and consulted for Theratechnologies and EMD Serono, unrelated to this work. NR 47 TC 22 Z9 22 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 13 PY 2012 VL 26 IS 5 BP 587 EP 597 DI 10.1097/QAD.0b013e32834f33cc PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 906GN UT WOS:000301333000008 PM 22112605 ER PT J AU Ouattara, EN Anglaret, X Wong, AY Chu, J Hsu, HE Danel, C Eholie, S Moh, R Gabillard, D Walensky, RP Freedberg, KA AF Ouattara, Eric N. Anglaret, Xavier Wong, Angela Y. Chu, Jennifer Hsu, Heather E. Danel, Christine Eholie, Serge Moh, Raoul Gabillard, Delphine Walensky, Rochelle P. Freedberg, Kenneth A. TI Projecting the clinical benefits and risks of using efavirenz-containing antiretroviral therapy regimens in women of childbearing age SO AIDS LA English DT Article DE antiretroviral therapy; efavirenz; pregnancy; sub-Saharan Africa; survival; teratogenicity; women ID HIV-INFECTED ADULTS; COTE-DIVOIRE; COST-EFFECTIVENESS; BIRTH-DEFECTS; INITIAL TREATMENT; CONTRACEPTIVE USE; 7-YEAR COHORT; WEST-AFRICA; NEVIRAPINE; PREGNANCY AB Objectives: To project the outcomes of using either efavirenz or nevirapine as part of initial antiretroviral therapy (ART) in women of childbearing age in Cote d'Ivoire. Methods: We used an HIV computer simulation model to project both the mother's survival and the birth defects at 10 years for a cohort of women who started ART with either efavirenz or nevirapine. The primary outcome was the ratio at 10 years of the difference in the number of women alive to the difference in the cumulative number of birth defects in women who started ART with efavirenz compared with nevirapine. In the base case analysis, the birth defect rate was 2.9% on efavirenz and 2.7% on nevirapine. In sensitivity analyses, we varied all inputs across confidence intervals reported in the literature. Results: In the base case analysis, for a cohort of 100 000 women, the additional number of women alive initiating ART with efavirenz at 10 years was 15 times the additional number of birth defects (women alive: nevirapine 67 969, efavirenz 68 880, difference 911; birth defects: nevirapine 1128, efavirenz 1187, difference 59). In sensitivity analysis, the teratogenicity rate with efavirenz had to be 6.3%, or 2.3 times higher than the rate with nevirapine, for the excess number of birth defects to outweigh the additional number of women alive at 10 years. Conclusion: In Cote d'Ivoire, initiating ART with efavirenz instead of nevirapine is likely to substantially increase the number of women alive at 10 years with a smaller potential number of birth defects. (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Ouattara, Eric N.; Anglaret, Xavier; Danel, Christine; Eholie, Serge; Moh, Raoul] CHU Treichville, PAC CI Program, Abidjan 01, Cote Ivoire. [Ouattara, Eric N.; Anglaret, Xavier; Danel, Christine; Gabillard, Delphine] Univ Bordeaux Segalen, Unite INSERM U897, Bordeaux, France. [Wong, Angela Y.; Chu, Jennifer; Hsu, Heather E.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. [Wong, Angela Y.; Chu, Jennifer; Hsu, Heather E.; Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Ouattara, EN (reprint author), CHU Treichville, PAC CI Program, 01 BP 1954, Abidjan 01, Cote Ivoire. EM eric.ouattara@isped.u-bordeaux2.fr RI Ghartouchent, malek/B-9088-2012; Anglaret, Xavier/F-7333-2013; OI Walensky, Rochelle P./0000-0002-8795-379X FU Agence Nationale de recherche sur le Sida et les hepatites virales, France [ANRS 12212]; National Institute of Allergy and Infectious Diseases, USA [R01 085276] FX This research was supported by the Agence Nationale de recherche sur le Sida et les hepatites virales (ANRS 12212), France and the National Institute of Allergy and Infectious Diseases (R01 085276), USA. NR 45 TC 5 Z9 5 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 13 PY 2012 VL 26 IS 5 BP 625 EP 634 DI 10.1097/QAD.0b013e328350fbfb PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 906GN UT WOS:000301333000012 PM 22398569 ER PT J AU Tanaka, A Shimada, K Tearney, GJ Kitabata, H Taguchi, H Fukuda, S Kashiwagi, M Kubo, T Takarada, S Hirata, K Mizukoshi, M Yoshikawa, J Bouma, BE Akasaka, T AF Tanaka, Atsushi Shimada, Kenei Tearney, Guillermo J. Kitabata, Hironori Taguchi, Haruyuki Fukuda, Shota Kashiwagi, Manabu Kubo, Takashi Takarada, Shigeho Hirata, Kumiko Mizukoshi, Masato Yoshikawa, Junichi Bouma, Brett E. Akasaka, Takashi TI "Framing" the Vessel The Critical Importance of Volumetric Analysis During Serial Intravascular Imaging Studies Reply SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID OPTICAL COHERENCE TOMOGRAPHY; ULTRASOUND; ANGINA; SPASM C1 [Tanaka, Atsushi] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Tanaka, A (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St, Boston, MA 02114 USA. EM atanaka1@partners.org NR 7 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 13 PY 2012 VL 59 IS 11 BP 1039 EP 1039 DI 10.1016/j.jacc.2011.11.042 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 904UF UT WOS:000301222700014 ER PT J AU Lin, L Bass, AJ Lockwood, WW Wang, ZW Silvers, AL Thomas, DG Chang, AC Lin, J Orringer, MB Li, WQ Glover, TW Giordano, TJ Lam, WL Meyerson, M Beer, DG AF Lin, Lin Bass, Adam J. Lockwood, William W. Wang, Zhuwen Silvers, Amy L. Thomas, Dafydd G. Chang, Andrew C. Lin, Jules Orringer, Mark B. Li, Weiquan Glover, Thomas W. Giordano, Thomas J. Lam, Wan L. Meyerson, Matthew Beer, David G. TI Activation of GATA binding protein 6 (GATA6) sustains oncogenic lineage-survival in esophageal adenocarcinoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lineage-survival oncogene; transcriptional reprogramming; extrinsic apoptosis pathway; p38 alpha and TNF-related apoptosis-inducing ligand activation ID TRANSCRIPTION FACTOR GENES; EMBRYONIC STEM-CELLS; BARRETTS-ESOPHAGUS; CANCER; DIFFERENTIATION; AMPLIFICATION; EXPRESSION; LUNG; ADDICTION; ENDODERM AB Gene amplification is a tumor-specific event during malignant transformation. Recent studies have proposed a lineage-dependency (addiction) model of human cancer whereby amplification of certain lineage transcription factors predisposes a survival mechanism in tumor cells. These tumor cells are derived from tissues where the lineage factors play essential developmental and maintenance roles. Here, we show that recurrent amplification at 18q11.2 occurs in 21% of esophageal adenocarcinomas (EAC). Utilization of an integrative genomic strategy reveals a single gene, the embryonic endoderm transcription factor GATA6, as the selected target of the amplification. Overexpression of GATA6 is found in EACs that contain gene amplification. We find that EAC patients whose tumors carry GATA6 amplification have a poorer survival. We show that ectopic expression of GATA6, together with FGFR2 isoform IIIb, increases anchorage-independent growth in immortalized Barrett's esophageal cells. Conversely, siRNA-mediated silencing of GATA6 significantly reduces both cell proliferation and anchorage-independent growth in EAC cells. We further demonstrate that induction of apoptotic/anoikis pathways is triggered upon silencing of GATA6 in EAC cells but not in esophageal squamous cells. We show that activation of p38 alpha signaling and up-regulation of TNF-related apoptosis-inducing ligand are detected in apoptotic EAC cells upon GATA6 deprivation. We conclude that selective gene amplification of GATA6 during EAC development sustains oncogenic lineage-survival of esophageal adenocarcinoma. C1 [Lin, Lin; Wang, Zhuwen; Silvers, Amy L.; Chang, Andrew C.; Lin, Jules; Orringer, Mark B.; Li, Weiquan; Beer, David G.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Thomas, Dafydd G.; Giordano, Thomas J.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Glover, Thomas W.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Bass, Adam J.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Bass, Adam J.; Meyerson, Matthew] Broad Inst Harvard, Boston, MA 02115 USA. [Bass, Adam J.; Meyerson, Matthew] MIT, Boston, MA 02115 USA. [Lockwood, William W.; Lam, Wan L.] British Columbia Canc Res Ctr, Dept Integrat Oncol, Vancouver, BC V5Z 1L3, Canada. RP Lin, L (reprint author), Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. EM linlin@umich.edu; dgbeer@umich.edu RI Li, Weiquan/B-4897-2011; Meyerson, Matthew/E-7123-2012 OI Chang, Andrew/0000-0001-9506-0425; Giordano, Thomas/0000-0003-0641-8873; FU National Cancer Institute [R01CA071606-12, K08CA134931, P50CA90578]; University of Michigan Surgery Research Advisory Committee (RAC) FX We thank Dr. Aarif Ahsan for sharing laboratory protocols; Drs. X. X. Xu and C. D. Capo-Chichi for the kind gifts of the pMT-CB6/GATA4 and pMT-CB6/GATA6 constructs. This work was supported by National Cancer Institute Grants R01CA071606-12 (to D.G.B.), K08CA134931 (to A.J.B.), P50CA90578 (to M.M.), and the University of Michigan Surgery Research Advisory Committee (RAC) Grant (to L.L.). NR 42 TC 29 Z9 29 U1 0 U2 2 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 MAR 13 PY 2012 VL 109 IS 11 BP 4251 EP 4256 DI 10.1073/pnas.1011989109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 907OH UT WOS:000301426700048 PM 22375031 ER PT J AU Ahonkhai, AA Noubary, F Munro, A Stark, R Wilke, M Freedberg, KA Wood, R Losina, E AF Ahonkhai, Aima A. Noubary, Farzad Munro, Alison Stark, Ruth Wilke, Marisa Freedberg, Kenneth A. Wood, Robin Losina, Elena TI Not All Are Lost: Interrupted Laboratory Monitoring, Early Death, and Loss to Follow-Up (LTFU) in a Large South African Treatment Program SO PLOS ONE LA English DT Article ID ANTIRETROVIRAL THERAPY PROGRAMS; HIV-INFECTED PATIENTS; PRIMARY-CARE; MORTALITY; RETENTION; ROUTINE; SERVICE; TRENDS; UGANDA; TESTS AB Background: Many HIV treatment programs in resource-limited settings are plagued by high rates of loss to follow-up (LTFU). Most studies have not distinguished between those who briefly interrupt, but return to care, and those more chronically lost to follow-up. Methods: We conducted a retrospective cohort study of 11,397 adults initiating antiretroviral therapy (ART) in 71 Southern African Catholic Bishops Conference/Catholic Relief Services HIV treatment clinics between January 2004 and December 2008. We distinguished among patients with early death, within the first 7 months on ART; patients with interruptions in laboratory monitoring (ILM), defined as missing visits in the first 7 months on ART, but returning to care by 12 months; and those LTFU, defined as missing all follow-up visits in the first 12 months on ART. We used multilevel logistic regression models to determine patient and clinic-level characteristics associated with these outcomes. Results: In the first year on ART, 60% of patients remained in care, 30% missed laboratory visits, and 10% suffered early death. Of the 3,194 patients who missed laboratory visits, 40% had ILM, resuming care by 12 months. After 12 months on ART, patients with ILM had a 30% increase in detectable viremia compared to those who remained in care. Risk of LTFU decreased with increasing enrollment year, and was lowest for patients who enrolled in 2008 compared to 2004 [OR 0.49, 95%CI 0.39-0.62]. Conclusions: In a large community-based cohort in South Africa, nearly 30% of patients miss follow-up visits for CD4 monitoring in the first year after starting ART. Of those, 40% have ILM but return to clinic with worse virologic outcomes than those who remain in care. The risk of chronic LTFU decreased with enrollment year. As ART availability increases, interruptions in care may become more common, and should be accounted for in addressing program LTFU. C1 [Ahonkhai, Aima A.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Noubary, Farzad; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Educ Ctr, Boston, MA 02114 USA. [Munro, Alison] So African Catholic Bishops Conf, Pretoria, Gauteng, South Africa. [Stark, Ruth; Wilke, Marisa] Catholic Relief Serv S Africa, Johannesburg, Gauteng, South Africa. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Freedberg, Kenneth A.; Losina, Elena] Harvard Univ Ctr AIDS Res, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Wood, Robin] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, ZA-7925 Cape Town, Western Cape, South Africa. [Wood, Robin] Univ Cape Town, Dept Med, ZA-7925 Cape Town, Western Cape, South Africa. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Ahonkhai, AA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM aahonkhai@partners.org FU National Institutes of Allergy and Infectious Disease [T32 A007433, R01 AI058736] FX Supported in part by National Institutes of Allergy and Infectious Disease (T32 A007433, R01 AI058736). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 16 Z9 17 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 12 PY 2012 VL 7 IS 3 AR e32993 DI 10.1371/journal.pone.0032993 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 920DF UT WOS:000302381500071 PM 22427925 ER PT J AU Temiyasathit, S Tang, WJ Leucht, P Anderson, CT Monica, SD Castillo, AB Helms, JA Stearns, T Jacobs, CR AF Temiyasathit, Sara Tang, W. Joyce Leucht, Philipp Anderson, Charles T. Monica, Stefanie D. Castillo, Alesha B. Helms, Jill A. Stearns, Tim Jacobs, Christopher R. TI Mechanosensing by the Primary Cilium: Deletion of Kif3A Reduces Bone Formation Due to Loading SO PLOS ONE LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; INTRAFLAGELLAR TRANSPORT PROTEINS; FLUID-FLOW; KINESIN-II; MOUSE; CELLS; OSTEOCYTES; EXPRESSION; MICE; SKELETOGENESIS AB Primary cilia, solitary microtubule-based structures that grow from the centriole and extend into the extracellular space, have increasingly been implicated as sensors of a variety of biochemical and biophysical signals. Mutations in primary cilium-related genes have been linked to a number of rare developmental disorders as well as dysregulation of cell proliferation. We propose that primary cilia are also important in mechanically regulated bone formation in adults and that their malfunction could play a role in complex multi-factorial bone diseases, such as osteoporosis. In this study, we generated mice with an osteoblast-and osteocyte-specific knockout of Kif3a, a subunit of the kinesin II intraflagellar transport (IFT) protein; IFT is required for primary cilia formation, maintenance, and function. These Col alpha 1(I) 2.3-Cre;Kif3a(fl/fl) mice exhibited no obvious morphological skeletal abnormalities. Skeletally mature Col alpha 1(I) 2.3-Cre;Kif3a(fl/fl) and control mice were exposed to 3 consecutive days of cyclic axial ulna loading, which resulted in a significant increase in bone formation in both the conditional knockouts and controls. However, Col alpha 1(I) 2.3-Cre;Kif3a(fl/fl) mice did exhibit decreased formation of new bone in response to mechanical ulnar loading compared to control mice. These results suggest that primary cilia act as cellular mechanosensors in bone and that their function may be critical for the regulation of bone physiology due to mechanical loading in adults. C1 [Temiyasathit, Sara; Tang, W. Joyce; Castillo, Alesha B.; Jacobs, Christopher R.] US Dept Vet Affairs, Bone & Joint Rehabil R&D Ctr, Palo Alto, CA USA. [Temiyasathit, Sara; Jacobs, Christopher R.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Stearns, Tim] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. [Jacobs, Christopher R.] Columbia Univ, Dept Biomed Engn, New York, NY USA. [Stearns, Tim] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Castillo, Alesha B.; Jacobs, Christopher R.] Stanford Univ, Dept Mech Engn, Stanford, CA 94305 USA. [Leucht, Philipp] Stanford Univ, Dept Orthopaed Surg, Stanford, CA 94305 USA. [Monica, Stefanie D.; Helms, Jill A.] Stanford Univ, Dept Surg Plast & Reconstruct Surg, Stanford, CA 94305 USA. [Anderson, Charles T.] Univ Calif Berkeley, Energy Biosci Inst, Berkeley, CA 94720 USA. RP Temiyasathit, S (reprint author), US Dept Vet Affairs, Bone & Joint Rehabil R&D Ctr, Palo Alto, CA USA. EM crj2111@columbia.edu RI Castillo, Alesha/A-8728-2014; OI Castillo, Alesha/0000-0002-1371-7567; Leucht, Philipp/0000-0002-8409-8513; Anderson, Charles/0000-0001-7481-3571 FU National Institutes of Health [R21AR054156]; Department of Veterans Affairs FX This work was supported by a National Institutes of Health grant R21AR054156 (CRJ), and ST was granted a fellowship by the Department of Veterans Affairs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 22 Z9 22 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 12 PY 2012 VL 7 IS 3 AR e33368 DI 10.1371/journal.pone.0033368 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 920DF UT WOS:000302381500135 PM 22428034 ER PT J AU Tso, FY Tully, DC Gonzalez, S Quince, C Ho, O Polacino, P Ruprecht, RM Hu, SL Wood, C AF Tso, For Yue Tully, Damien C. Gonzalez, Sandra Quince, Christopher Ho, On Polacino, Patricia Ruprecht, Ruth M. Hu, Shiu-Lok Wood, Charles TI Dynamics of Envelope Evolution in Clade C SHIV-Infected Pig-Tailed Macaques during Disease Progression Analyzed by Ultra-Deep Pyrosequencing SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIBODY NEUTRALIZATION; HIV-1 TRANSMISSION; MACACA-NEMESTRINA; ZAMBIAN INFANT; V3 LOOP; TYPE-1; ENV; CORECEPTOR; SEQUENCES AB Understanding the evolution of the human immunodeficiency virus type 1 (HIV-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (SHIV) infection of non-human primate provides an ideal platform for such studies. A newly developed clade C SHIV, SHIV-1157ipd3N4, which was able to infect rhesus macaques, closely resembled primary HIV-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. One of the infected animals subsequently progressed to AIDS, whereas one remained a non-progressor. The viral envelope evolution in the infected animals during disease progression was analyzed by a bioinformatics approach using ultra-deep pyrosequencing. Our results showed substantial envelope variations emerging in the progressor animal after the onset of AIDS. These envelope variations impacted the length of the variable loops and charges of different envelope regions. Additionally, multiple mutations were located at the CD4 and CCR5 binding sites, potentially affecting receptor binding affinity, viral fitness and they might be selected at late stages of disease. More importantly, these envelope mutations are not random since they had repeatedly been observed in a rhesus macaque and a human infant infected by either SHIV or HIV-1, respectively, carrying the parental envelope of the infectious molecular clone SHIV-1157ipd3N4. Moreover, similar mutations were also observed from other studies on different clades of envelopes regardless of the host species. These recurring mutations in different envelopes suggest that there may be a common evolutionary pattern and selection pathway for the HIV-1 envelope during disease progression. C1 [Tso, For Yue; Tully, Damien C.; Gonzalez, Sandra; Wood, Charles] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA. [Tso, For Yue; Tully, Damien C.; Gonzalez, Sandra; Wood, Charles] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA. [Ho, On; Hu, Shiu-Lok] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. [Polacino, Patricia; Hu, Shiu-Lok] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. [Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Quince, Christopher] Univ Glasgow, Sch Engn, Glasgow, Lanark, Scotland. RP Tso, FY (reprint author), Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA. EM cwood@unlnotes.unl.edu RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU Public Health Service [CA75903, TW001429, T32 AI060547]; National Center for Research Resource, Center for Biomedical Research Excellence [P30 RR031151, P01 AI48240, RR000166, N01 AI060006]; American Recovery and Reinvestment Act [3P01AI048240-08S1]; National Institute of Allergy and Infectious Disease FX This work was supported by Public Health Service grants, CA75903, TW001429, T32 AI060547 and National Center for Research Resource, Center for Biomedical Research Excellence grant P30 RR031151 to CW; P01 AI48240 to RMR, CW and SLH; and RR000166 and N01 AI060006 to the Washington National Primate Research Center; American Recovery and Reinvestment Act funding 3P01AI048240-08S1 to RMR, CW; SG was supported by a Ruth L. Kirschstein National Service Award from the National Institute of Allergy and Infectious Disease. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 2 Z9 4 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 12 PY 2012 VL 7 IS 3 AR e32827 DI 10.1371/journal.pone.0032827 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 920DF UT WOS:000302381500053 PM 22427893 ER PT J AU Walker, RH Moore, C Davies, G Dirling, LB Koch, RJ Meshul, CK AF Walker, Ruth H. Moore, Cindy Davies, Georgia Dirling, Lisa B. Koch, Rick J. Meshul, Charles K. TI Effects of Subthalamic Nucleus Lesions and Stimulation upon Corticostriatal Afferents in the 6-Hydroxydopamine- Lesioned Rat SO PLOS ONE LA English DT Article ID HIGH-FREQUENCY STIMULATION; DEEP-BRAIN-STIMULATION; MEDIUM SPINY NEURONS; INDUCED CONTRALATERAL ROTATIONS; EXTRACELLULAR GLUTAMATE LEVELS; TIME-DEPENDENT CHANGES; NIGRA PARS RETICULATA; HEMI-PARKINSON RATS; L-DOPA TREATMENT; STRIATAL GLUTAMATE AB Abnormalities of striatal glutamate neurotransmission may play a role in the pathophysiology of Parkinson's disease and may respond to neurosurgical interventions, specifically stimulation or lesioning of the subthalamic nucleus (STN). The major glutamatergic afferent pathways to the striatum are from the cortex and thalamus, and are thus likely to be sources of striatal neuronally-released glutamate. Corticostriatal terminals can be distinguished within the striatum at the electron microscopic level as their synaptic vesicles contain the vesicular glutamate transporter, VGLUT1. The majority of terminals which are immunolabeled for glutamate but are not VGLUT1 positive are likely to be thalamostriatal afferents. We compared the effects of short term, high frequency, STN stimulation and lesioning in 6-hydroxydopamine (6OHDA)-lesioned rats upon striatal terminals immunolabeled for both presynaptic glutamate and VGLUT1. 6OHDA lesions resulted in a small but significant increase in the proportions of VGLUT1-labeled terminals making synapses on dendritic shafts rather than spines. STN stimulation for one hour, but not STN lesions, increased the proportion of synapses upon spines. The density of presynaptic glutamate immuno-gold labeling was unchanged in both VGLUT1-labeled and -unlabeled terminals in 6OHDA-lesioned rats compared to controls. Rats with 6OHDA lesions+STN stimulation showed a decrease in nerve terminal glutamate immuno-gold labeling in both VGLUT1-labeled and -unlabeled terminals. STN lesions resulted in a significant decrease in the density of presynaptic immuno-gold-labeled glutamate only in VGLUT1-labeled terminals. STN interventions may achieve at least part of their therapeutic effect in PD by normalizing the location of corticostriatal glutamatergic terminals and by altering striatal glutamatergic neurotransmission. C1 [Walker, Ruth H.; Davies, Georgia; Koch, Rick J.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Moore, Cindy; Dirling, Lisa B.; Meshul, Charles K.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Neurocytol Lab, Res Serv, Portland, OR 97201 USA. [Meshul, Charles K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci & Pathol, Portland, OR 97201 USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. EM ruth.walker@mssm.edu FU Department of Veterans Affairs FX This work was funded by Department of Veterans Affairs Merit awards to RHW and CKM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 78 TC 7 Z9 7 U1 2 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 12 PY 2012 VL 7 IS 3 AR e32919 DI 10.1371/journal.pone.0032919 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 920DF UT WOS:000302381500062 PM 22427909 ER PT J AU Nakamura, K Berry, NC An, PG Dudzinski, DM AF Nakamura, Kenta Berry, Natalia C. An, Perry G. Dudzinski, David M. TI Significance of ST-Segment Elevation in Lead aVR SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY; LEFT MAIN; ELECTROCARDIOGRAPHY; V-1 C1 [Nakamura, Kenta; Berry, Natalia C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Dudzinski, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. [An, Perry G.] Newton Wellesley Hosp, Dept Med, Newton, MA USA. RP Nakamura, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 55 Fruit St,Med GRB 740, Boston, MA 02114 USA. EM knakamura@partners.org NR 10 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 12 PY 2012 VL 172 IS 5 BP 389 EP 391 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 906XB UT WOS:000301381300002 PM 22412103 ER PT J AU Luo, JH Rossouw, J Tong, E Giovino, GA Lee, C Chen, C Ockene, JK Qi, LH Margolis, KL AF Luo, Juhua Rossouw, Jacques Tong, Elisa Giovino, Gary A. Lee, Cathy Chen, Chu Ockene, Judith K. Qi, Lihong Margolis, Karen L. TI Smoking Cessation, Weight Gain, and Risk of Type 2 Diabetes Mellitus Among Postmenopausal Women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID METAANALYSIS; COHORT C1 [Luo, Juhua] W Virginia Univ, Dept Community Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. [Rossouw, Jacques] NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Tong, Elisa] Univ Calif, Davis Med Ctr, Div Gen Internal Med, Sacramento, CA USA. [Giovino, Gary A.] SUNY Buffalo, Sch Publ Hlth & Hlth Profess, Dept Community Hlth & Hlth Behav, Buffalo, NY 14260 USA. [Lee, Cathy] Univ Calif Los Angeles, David Geffen Sch Med, Dept Internal Med, Div Geriatr, Los Angeles, CA 90095 USA. [Lee, Cathy] Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. [Chen, Chu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Ockene, Judith K.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Qi, Lihong] Univ Calif Davis, Dept Publ Hlth Sci, Davis, CA 95616 USA. [Margolis, Karen L.] HealthPartners Res Fdn, Minneapolis, MN USA. RP Luo, JH (reprint author), W Virginia Univ, Dept Community Med, Mary Babb Randolph Canc Ctr, Morgantown, WV 26506 USA. EM Jiluo@hsc.wvu.edu NR 9 TC 10 Z9 10 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 12 PY 2012 VL 172 IS 5 BP 438 EP 440 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 906XB UT WOS:000301381300017 PM 22412112 ER PT J AU Hajjar, I Hart, M Chen, YL Mack, W Milberg, W Chui, H Lipsitz, L AF Hajjar, Ihab Hart, Meaghan Chen, Yu-Ling Mack, Wendy Milberg, William Chui, Helena Lipsitz, Lewis TI Effect of Antihypertensive Therapy on Cognitive Function in Early Executive Cognitive Impairment: A Double-blind Randomized Clinical Trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID II TYPE-2 RECEPTOR; HEALTH; HYPERTENSION; DEMENTIA; BRAIN C1 [Hajjar, Ihab] Univ So Calif, Dept Med, Los Angeles, CA 90033 USA. [Hajjar, Ihab] Univ So Calif, Div Geriatr, Hos & Gen Internal Med, Los Angeles, CA 90033 USA. [Chen, Yu-Ling] Univ So Calif, Alzheimer Dis Res Ctr, Dept Neurol, Los Angeles, CA 90033 USA. [Mack, Wendy] Univ So Calif, Dept Biostat, Los Angeles, CA 90033 USA. [Chui, Helena] Univ So Calif, Dept Neurol, Raymond & Betty McCarron Chair Neurol, Los Angeles, CA 90033 USA. [Hart, Meaghan; Lipsitz, Lewis] Inst Aging Res, Boston, MA USA. [Milberg, William] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Milberg, William] VA Boston Healthcare, New England Geriatr Res, Educ & Clin Ctr GRECC, Boston Div, Boston, MA USA. [Lipsitz, Lewis] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. RP Hajjar, I (reprint author), Univ So Calif, Dept Med, 2020 Zonal Ave,IRD 320, Los Angeles, CA 90033 USA. EM ihajjar@usc.edu FU NCATS NIH HHS [UL1 TR000130]; NCRR NIH HHS [UL1RR031986]; NIA NIH HHS [1 K23 AG030057, K23 AG030057, P01 AG004390, P01-AG004390, R37 AG025037, R37-AG025037] NR 8 TC 31 Z9 32 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 12 PY 2012 VL 172 IS 5 BP 442 EP 444 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 906XB UT WOS:000301381300019 PM 22412114 ER PT J AU Juric, D Baselga, J AF Juric, Dejan Baselga, Jose TI Tumor Genetic Testing for Patient Selection in Phase I Clinical Trials: The Case of PI3K Inhibitors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID DUAL PI3K/MTOR INHIBITOR; BREAST-CANCER CELLS; HEDGEHOG PATHWAY; MUTATIONS; SENSITIVITY; NVP-BEZ235; BRAF C1 [Juric, Dejan; Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Baselga, Jose] Harvard Univ, Sch Med, Boston, MA USA. RP Juric, D (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 18 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2012 VL 30 IS 8 BP 765 EP 766 DI 10.1200/JCO.2011.39.6390 PG 2 WC Oncology SC Oncology GA 923NS UT WOS:000302626600005 PM 22271482 ER PT J AU Hershman, DL Wilde, ET Wright, JD Buono, DL Kalinsky, K Malin, JL Neugut, AI AF Hershman, Dawn L. Wilde, Elizabeth T. Wright, Jason D. Buono, Donna L. Kalinsky, Kevin Malin, Jennifer L. Neugut, Alfred I. TI Uptake and Economic Impact of First-Cycle Colony-Stimulating Factor Use During Adjuvant Treatment of Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SINGLE-ADMINISTRATION PEGFILGRASTIM; ACUTE MYELOID-LEUKEMIA; DAILY FILGRASTIM; DOSE-DENSE; MYELODYSPLASTIC SYNDROME; SURGEON CHARACTERISTICS; CONSERVATION SURGERY; RANDOMIZED-TRIAL; PHASE-III; CHEMOTHERAPY AB Purpose In 2002, pegfilgrastim was approved by the US Food and Drug Administration and the benefits of dose-dense breast cancer chemotherapy, especially for hormone receptor (HR)-negative tumors, were reported. We examined first-cycle colony-stimulating factor use (FC-CSF) before and after 2002 and estimated US expenditures for dose-dense chemotherapy. Methods We identified patients in Surveillance, Epidemiology, and End Results-Medicare greater than 65 years old with stages I to III breast cancer who had greater than one chemotherapy claim within 6 months of diagnosis(1998 to 2005) and classified patients with an average cycle length less than 21 days as having received dose-dense chemotherapy. The associations of patient, tumor, and physician-related factors with the receipt of any colony-stimulating factor (CSF) and FC-CSF use were analyzed by using generalized estimating equations. CSF costs were estimated for patients who were undergoing dose-dense chemotherapy. Results Among the 10,773 patients identified, 5,266 patients (48.9%) had a CSF claim. CSF use was stable between 1998 and 2002 and increased from 36.8% to 73.7% between 2002 and 2005, FC-CSF use increased from 13.2% to 67.9%, and pegfilgrastim use increased from 4.1% to 83.6%. In a multivariable analysis, CSF use was associated with age and chemotherapy type and negatively associated with black/Hispanic race, rural residence, and shorter chemotherapy duration. FC-CSF use was associated with high socioeconomic status but not with age or race/ethnicity. The US annual CSF expenditure for women with HR-positive tumors treated with dose-dense chemotherapy is estimated to be $38.8 million. Conclusion A rapid increase in FC-CSF use occurred over a short period of time, which was likely a result of the reported benefits of dose-dense chemotherapy and the ease of pegfilgrastim administration. Because of the increasing evidence that elderly HR-positive patients do not benefit from dose-dense chemotherapy, limiting pegfilgrastim use would combat the increasing costs of cancer care. J Clin Oncol 30: 806-812. (C) 2012 by American Society of Clinical Oncology C1 [Hershman, Dawn L.] Columbia Univ, Med Ctr, New York, NY 10032 USA. [Hershman, Dawn L.; Wilde, Elizabeth T.; Wright, Jason D.; Buono, Donna L.; Kalinsky, Kevin; Neugut, Alfred I.] New York Presbyterian Hosp, New York, NY USA. [Malin, Jennifer L.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Hershman, DL (reprint author), Columbia Univ, Med Ctr, 161 Ft Washington Ave,10-1068, New York, NY 10032 USA. EM dlh23@columbia.edu FU National Cancer Institute [NCI R01CA134964] FX Supported by Grant No. NCI R01CA134964 from the National Cancer Institute (D.L.H.). NR 30 TC 18 Z9 20 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2012 VL 30 IS 8 BP 806 EP 812 DI 10.1200/JCO.2011.37.7499 PG 7 WC Oncology SC Oncology GA 923NS UT WOS:000302626600015 PM 22312106 ER PT J AU Bergethon, K Shaw, AT Ou, SHI Katayama, R Lovly, CM McDonald, NT Massion, PP Siwak-Tapp, C Gonzalez, A Fang, R Mark, EJ Batten, JM Chen, HQ Wilner, KD Kwak, EL Clark, JW Carbone, DP Ji, HB Engelman, JA Mino-Kenudson, M Pao, W Iafrate, AJ AF Bergethon, Kristin Shaw, Alice T. Ou, Sai-Hong Ignatius Katayama, Ryohei Lovly, Christine M. McDonald, Nerina T. Massion, Pierre P. Siwak-Tapp, Christina Gonzalez, Adriana Fang, Rong Mark, Eugene J. Batten, Julie M. Chen, Haiquan Wilner, Keith D. Kwak, Eunice L. Clark, Jeffrey W. Carbone, David P. Ji, Hongbin Engelman, Jeffrey A. Mino-Kenudson, Mari Pao, William Iafrate, A. John TI ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANAPLASTIC LYMPHOMA KINASE; FUSION; GLIOBLASTOMA; GEFITINIB; EML4-ALK; MUTATIONS; TUMORS; GENE; INHIBITORS; FEATURES AB Purpose Chromosomal rearrangements involving the ROS1 receptor tyrosine kinase gene have recently been described in a subset of non-small-cell lung cancers (NSCLCs). Because little is known about these tumors, we examined the clinical characteristics and treatment outcomes of patients with NSCLC with ROS1 rearrangement. Patients and Methods Using a ROS1 fluorescent in situ hybridization (FISH) assay, we screened 1,073 patients with NSCLC and correlated ROS1 rearrangement status with clinical characteristics, overall survival, and when available, ALK rearrangement status. In vitro studies assessed the responsiveness of cells with ROS1 rearrangement to the tyrosine kinase inhibitor crizotinib. The clinical response of one patient with ROS1-rearranged NSCLC to crizotinib was investigated as part of an expanded phase I cohort. Results Of 1,073 tumors screened, 18 (1.7%) were ROS1 rearranged by FISH, and 31 (2.9%) were ALK rearranged. Compared with the ROS1-negative group, patients with ROS1 rearrangements were significantly younger and more likely to be never-smokers (each P < .001). All of the ROS1-positive tumors were adenocarcinomas, with a tendency toward higher grade. ROS1-positive and-negative groups showed no difference in overall survival. The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib. The patient treated with crizotinib showed tumor shrinkage, with a near complete response. Conclusion ROS1 rearrangement defines a molecular subset of NSCLC with distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC. J Clin Oncol 30: 863-870. (C) 2012 by American Society of Clinical Oncology C1 [Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ou, Sai-Hong Ignatius; Siwak-Tapp, Christina] Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA USA. [Wilner, Keith D.] Pfizer, La Jolla, CA USA. [Lovly, Christine M.; McDonald, Nerina T.; Massion, Pierre P.; Gonzalez, Adriana; Carbone, David P.; Pao, William] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Massion, Pierre P.] Nashville Vet Affairs Med Ctr, Nashville, TN USA. [Fang, Rong; Ji, Hongbin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China. [Chen, Haiquan] Fudan Univ, Shanghai Canc Ctr, Shanghai 200433, Peoples R China. [Chen, Haiquan] Fudan Univ, Shanghai Med Coll, Shanghai 200433, Peoples R China. RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM aiafrate@partners.org FU National Institutes of Health [1R21CA161590-01]; Pfizer FX Supported by National Institutes of Health Grant No. 1R21CA161590-01 (A.J.I.) and by Pfizer, which supported the crizotinib phase I trial. NR 22 TC 493 Z9 532 U1 10 U2 50 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2012 VL 30 IS 8 BP 863 EP 870 DI 10.1200/JCO.2011.35.6345 PG 8 WC Oncology SC Oncology GA 923NS UT WOS:000302626600023 PM 22215748 ER PT J AU Schutz, FAB Je, YJ Richards, CJ Choueiri, TK AF Schutz, Fabio A. B. Je, Youjin Richards, Christopher J. Choueiri, Toni K. TI Meta-Analysis of Randomized Controlled Trials for the Incidence and Risk of Treatment-Related Mortality in Patients With Cancer Treated With Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; ADVANCED HEPATOCELLULAR-CARCINOMA; FOOT SKIN REACTION; PHASE-III; CLINICAL-TRIALS; DOUBLE-BLIND; LUNG-CANCER; SORAFENIB; SUNITINIB; ANGIOGENESIS AB Purpose Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have become the cornerstone in the treatment of several malignancies. These drugs have also been associated with an increase in the risk of potentially life-threatening adverse events, such as arterial thrombotic events, bleeding, congestive heart failure, and others. We performed an up-to-date meta-analysis to determine the risk of fatal adverse events (FAEs) in patients with cancer treated with VEGFR TKIs. Methods MEDLINE and PubMed databases were searched for articles published from January 1966 to February 2011. Eligible studies were limited to trials of US Food and Drug Administration-approved VEGFR TKIs (pazopanib, sunitinib, and sorafenib) that reported on patients with cancer with any primary tumor type, randomized design, and adequate safety profile. Statistical analyses were conducted to calculate the summary incidence, relative risk (RR), and 95% CIs by using random-effects or fixed-effects models on the basis of the heterogeneity of included studies. Results In all, 4,679 patients from 10 randomized controlled trials (RCTs) were included, with 2,856 from sorafenib, 1,388 from sunitinib, and 435 from pazopanib trials. The incidence of FAEs related to VEGFR TKIs was 1.5% (95% CI, 0.8% to 2.4%) with an RR of 2.23 (95% CI, 1.12 to 4.44; P = .023) compared with control patients. On subgroup analysis, no difference in the rate of FAEs was found between different VEGFR TKIs or tumor types. No evidence of publication bias was observed. Conclusion In a meta-analysis of RCTs, the use of VEGFR TKIs was associated with an increased risk of FAEs compared with control patients. J Clin Oncol 30: 871-877. (C) 2012 by American Society of Clinical Oncology C1 [Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Schutz, Fabio A. B.; Richards, Christopher J.; Choueiri, Toni K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Je, Youjin] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Schutz, Fabio A. B.] Hosp Sao Jose & Beneficencia Portuguesa Sao Paulo, Sao Paulo, Brazil. RP Choueiri, TK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,DANA 1230, Boston, MA 02215 USA. EM toni_choueiri@dfci.harvard.edu FU Trust Family FX Supported by the Trust Family Research Fund for Kidney Cancer. NR 45 TC 75 Z9 75 U1 4 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2012 VL 30 IS 8 BP 871 EP 877 DI 10.1200/JCO.2011.37.1195 PG 7 WC Oncology SC Oncology GA 923NS UT WOS:000302626600024 PM 22312105 ER PT J AU Janne, PA Meyerson, M AF Jaenne, Pasi A. Meyerson, Matthew TI ROS1 Rearrangements in Lung Cancer: A New Genomic Subset of Lung Adenocarcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID ANAPLASTIC LYMPHOMA KINASE; CHEMOTHERAPY; MUTATIONS; GEFITINIB; EGFR C1 [Jaenne, Pasi A.; Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jaenne, Pasi A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Meyerson, Matthew] Broad Inst, Cambridge, MA USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Meyerson, Matthew/E-7123-2012 NR 15 TC 26 Z9 26 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2012 VL 30 IS 8 BP 878 EP 879 DI 10.1200/JCO.2011.39.4197 PG 2 WC Oncology SC Oncology GA 923NS UT WOS:000302626600025 PM 22215755 ER PT J AU Smith, TJ Temin, S Alesi, ER Abernethy, AP Balboni, TA Basch, EM Ferrell, BR Loscalzo, M Meier, DE Paice, JA Peppercorn, JM Somerfield, M Stovall, E Von Roenn, JH AF Smith, Thomas J. Temin, Sarah Alesi, Erin R. Abernethy, Amy P. Balboni, Tracy A. Basch, Ethan M. Ferrell, Betty R. Loscalzo, Matt Meier, Diane E. Paice, Judith A. Peppercorn, Jeffrey M. Somerfield, Mark Stovall, Ellen Von Roenn, Jamie H. TI American Society of Clinical Oncology Provisional Clinical Opinion: The Integration of Palliative Care Into Standard Oncology Care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CELL LUNG-CANCER; MEDICINE CONSULTATION; OUTPATIENT; INTERVENTION; OUTCOMES; THERAPY; COSTS; TEAM; LIFE AB Based on strong evidence from a phase III RCT, patients with metastatic non-small-cell lung cancer should be offered concurrent palliative care and standard oncologic care at initial diagnosis. While a survival benefit from early involvement of palliative care has not yet been demonstrated in other oncology settings, substantial evidence demonstrates that palliative care-when combined with standard cancer care or as the main focus of care-leads to better patient and caregiver outcomes. These include improvement in symptoms, QOL, and patient satisfaction, with reduced caregiver burden. Earlier involvement of palliative care also leads to more appropriate referral to and use of hospice, and reduced use of futile intensive care. While evidence clarifying optimal delivery of palliative care to improve patient outcomes is evolving, no trials to date have demonstrated harm to patients and caregivers, or excessive costs, from early involvement of palliative care. Therefore, it is the Panel's expert consensus that combined standard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and/or high symptom burden. Strategies to optimize concurrent palliative care and standard oncology care, with evaluation of its impact on important patient and caregiver outcomes (eg, QOL, survival, health care services utilization, and costs) and on society, should be an area of intense research. C1 [Smith, Thomas J.] Sidney Kimmel Canc Ctr Johns Hopkins Med, Baltimore, MD USA. [Stovall, Ellen] Natl Coalit Canc Survivorship, Silver Spring, MD USA. [Temin, Sarah; Somerfield, Mark] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. [Alesi, Erin R.] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. [Abernethy, Amy P.; Peppercorn, Jeffrey M.] Duke Univ, Med Ctr, Durham, NC USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Basch, Ethan M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Meier, Diane E.] Mt Sinai Sch Med, Ctr Adv Palliat Care, New York, NY USA. [Ferrell, Betty R.; Loscalzo, Matt] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Paice, Judith A.; Von Roenn, Jamie H.] Northwestern Univ, Chicago, IL 60611 USA. RP Temin, S (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM guidelines@asco.org OI Paice, Judith/0000-0001-7534-1756 NR 31 TC 402 Z9 406 U1 8 U2 51 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2012 VL 30 IS 8 BP 880 EP 887 DI 10.1200/JCO.2011.38.5161 PG 8 WC Oncology SC Oncology GA 923NS UT WOS:000302626600026 PM 22312101 ER PT J AU Mroz, EA Forastiere, AA Rocco, JW AF Mroz, Edmund A. Forastiere, Arlene A. Rocco, James W. TI Epidermal Growth Factor Receptor and the Changing Face of Oropharyngeal Cancer Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 [Mroz, Edmund A.; Rocco, James W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Forastiere, Arlene A.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Rocco, James W.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Mroz, EA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2012 VL 30 IS 8 BP 891 EP 892 DI 10.1200/JCO.2011.40.6884 PG 3 WC Oncology SC Oncology GA 923NS UT WOS:000302626600032 ER PT J AU Tse, WKF Chow, SC Wong, CKC AF Tse, William K. F. Chow, Sheung C. Wong, Chris K. C. TI Eel osmotic stress transcriptional factor 1 (Ostf1) is highly expressed in gill mitochondria-rich cells, where ERK phosphorylated SO FRONTIERS IN ZOOLOGY LA English DT Article DE Immunohistochemical staining; Mitochondria-rich cells; Osmotic stress transcriptional factor 1 ID ANGUILLA-JAPONICA; PAVEMENT CELLS; JAPANESE EEL; ACTIVATION; PATHWAYS; EXCHANGE; CULTURE; ATPASE AB Background: Osmotic stress transcriptional factor 1 (Ostf1) was firstly identified in tilapia in 2005. Then numerous studies have investigated its regulation and expression profile in fish gill tissues in related to osmoregulation. Generally, hyperosmotic stress induced ostf1 mRNA expression level, however there is no report studying the cellular localization of Ostf1 expression in any osmoregulatory tissue. In this study immunohistochemical (IHC) approach was used to study the cellular localization of Ostf1 in gill cells of Japanese eels. Findings: Ostf1 protein was found to be localized in branchial mitochondria-rich/chloride cell (MRC/CC) as revealed by Na alpha 5 and CFTR co-localization. The protein was detectable at day 3 after fresh water to seawater transfer and was mainly localized in MRCs. Moreover, elevated levels of extracellular signal regulated kinase (ERK) phosphorylation was observed at day 3 of the transfer and was co-localized with MRCs. Conclusions: Our data identified Ostf1 expression in gill MRCs. The observation supports the role of Ostf1 in osmosensing and/or osmoregulation in fish gills, particularly its functional relationship with MRCs. The observation of the co-expression of pERK and Ostf1 in MRCs suggests a cross-talk mechanism between the mitogen-activated protein kinases (MAPKs) and Ostf1 in response to hyperosmotic challenge. To summarize, this report has addressed the cellular localization of Ostf1 and provides evidence to illustrate the involvement of Ostf1 and ERK on osmosensing and osmoregulatory function of gill MRCs. C1 [Tse, William K. F.; Chow, Sheung C.; Wong, Chris K. C.] Hong Kong Baptist Univ, Dept Biol, Kowloon Tong, Hong Kong, Peoples R China. [Tse, William K. F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA USA. RP Tse, WKF (reprint author), Hong Kong Baptist Univ, Dept Biol, Kowloon Tong, Hong Kong, Peoples R China. EM kftse@partners.org; ckcwong@hkbu.edu.hk RI TSE, KA FAI WILLIAM/C-9384-2012 OI TSE, KA FAI WILLIAM/0000-0002-3738-0460 FU University Grants Committee [HKBU 261610] FX This work was supported by General Research Fund (HKBU 261610), University Grants Committee to CKCW. NR 14 TC 10 Z9 10 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-9994 J9 FRONT ZOOL JI Front. Zool. PD MAR 10 PY 2012 VL 9 AR 3 DI 10.1186/1742-9994-9-3 PG 5 WC Zoology SC Zoology GA 921LH UT WOS:000302478600001 PM 22405401 ER PT J AU Ptaszek, LM Mansour, M Ruskin, JN Chien, KR AF Ptaszek, Leon M. Mansour, Moussa Ruskin, Jeremy N. Chien, Kenneth R. TI Towards regenerative therapy for cardiac disease SO LANCET LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; BONE-MARROW-CELLS; HEMATOPOIETIC STEM-CELLS; PROGENITOR CELLS; MYOBLAST TRANSPLANTATION; INTRACORONARY INJECTION; HEART REGENERATION; MAMMALIAN HEART; DEFINED FACTORS; SMOOTH-MUSCLE AB Development of regenerative therapeutic strategies to reverse the progression of advanced heart failure is one of the most urgent clinical needs of this century. Insights gained from clinical trials of adult stem cells, together with fundamental scientific advances in cardiac stem cell and regenerative biology, are beginning to yield potential new targets and strategies for regenerative therapies. Of particular importance are new scientific discoveries related to intrinsic cardiac regeneration, renewal factors that can trigger regeneration, and tissue-engineering technology, which are beginning to change the way investigators view the scientific and clinical position of cardiovascular regenerative therapy. C1 [Ptaszek, Leon M.; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ptaszek, Leon M.; Mansour, Moussa; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Ctr Heart, Boston, MA 02114 USA. [Ptaszek, Leon M.; Mansour, Moussa; Ruskin, Jeremy N.] Harvard Univ, Sch Med, Boston, MA USA. [Ptaszek, Leon M.; Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Chien, KR (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St,CPZN 3250, Boston, MA 02114 USA. EM kchien@harvard.edu FU de Gunzburg Family Foundation; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke at the Massachusetts General Hospital (Boston, MA, USA) FX We apologise to those of our colleagues whose work could not be cited because of constraints on space. LMP thanks the de Gunzburg Family Foundation and the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke at the Massachusetts General Hospital (Boston, MA, USA) for their support. NR 82 TC 111 Z9 113 U1 5 U2 47 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR 10 PY 2012 VL 379 IS 9819 BP 933 EP 942 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 906NY UT WOS:000301353700034 PM 22405796 ER PT J AU Altshuler, D AF Altshuler, David TI 2011 Curt Stern Award Address SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material C1 [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol & Med, Boston, MA 02114 USA. [Altshuler, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Altshuler, D (reprint author), Massachusetts Gen Hosp, Dept Mol Biol & Med, Boston, MA 02114 USA. EM altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR 9 PY 2012 VL 90 IS 3 BP 407 EP 409 DI 10.1016/j.ajhg.2012.02.017 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 911ZI UT WOS:000301762800006 PM 22405086 ER PT J AU Saxena, R Elbers, CC Guo, YR Peter, I Gaunt, TR Mega, JL Lanktree, MB Tare, A Castillo, BA Li, YR Johnson, T Bruinenberg, M Gilbert-Diamond, D Rajagopalan, R Voight, BF Balasubramanyam, A Barnard, J Bauer, F Baumert, J Bhangale, T Bohm, BO Braund, PS Burton, PR Chandrupatla, HR Clarke, R Cooper-DeHoff, RM Crook, ED Davey-Smith, G Day, IN de Boer, A de Groot, MCH Drenos, F Ferguson, J Fox, CS Furlong, CE Gibson, Q Gieger, C Gilhuijs-Pederson, LA Glessner, JT Goel, A Gong, Y Grant, SFA Grobbee, DE Hastie, C Humphries, SE Kim, CE Kivimaki, M Kleber, M Meisinger, C Kumari, M Langaee, TY Lawlor, DA Li, MY Lobmeyer, MT Maitland-van der Zee, AH Meijs, MFL Molony, CM Morrow, DA Murugesan, G Musani, SK Nelson, CP Newhouse, SJ O'Connell, JR Padmanabhan, S Palmen, J Patel, SR Pepine, CJ Pettinger, M Price, TS Rafelt, S Ranchalis, J Rasheed, A Rosenthal, E Ruczinski, I Shah, S Shen, HQ Silbernagel, G Smith, EN Spijkerman, AWM Stanton, A Steffes, MW Thorand, B Trip, M van der Harst, P van der A, DL van Iperen, EPA van Setten, J van Vliet-Ostaptchouk, JV Verweij, N Wolffenbuttel, BHR Young, T Zafarmand, MH Zmuda, JM Boehnke, M Altshuler, D McCarthy, M Kao, WHL Pankow, JS Cappola, TP Sever, P Poulter, N Caulfield, M Dominiczak, A Shields, DC Bhatt, DL Zhang, L Curtis, SP Danesh, J Casas, JP van der Schouw, YT Onland-Moret, NC Doevendans, PA Dorn, GW Farrall, M FitzGerald, GA Hamsten, A Hegele, R Hingorani, AD Hofker, MH Huggins, GS Illig, T Jarvik, GP Johnson, JA Klungel, OH Knowler, WC Koenig, W Marz, W Meigs, JB Melander, O Munroe, PB Mitchell, BD Bielinski, SJ Rader, DJ Reilly, MP Rich, SS Rotter, JI Saleheen, D Samani, NJ Schadt, EE Shuldiner, AR Silverstein, R Kottke-Marchant, K Talmud, PJ Watkins, H Asselbergs, FW de Bakker, PIW McCaffery, J Wijmenga, C Sabatine, MS Wilson, JG Reiner, A Bowden, DW Hakonarson, H Siscovick, DS Keating, BJ AF Saxena, Richa Elbers, Clara C. Guo, Yiran Peter, Inga Gaunt, Tom R. Mega, Jessica L. Lanktree, Matthew B. Tare, Archana Almoguera Castillo, Berta Li, Yun R. Johnson, Toby Bruinenberg, Marcel Gilbert-Diamond, Diane Rajagopalan, Ramakrishnan Voight, Benjamin F. Balasubramanyam, Ashok Barnard, John Bauer, Florianne Baumert, Jens Bhangale, Tushar Boehm, Bernhard O. Braund, Peter S. Burton, Paul R. Chandrupatla, Hareesh R. Clarke, Robert Cooper-DeHoff, Rhonda M. Crook, Errol D. Davey-Smith, George Day, Ian N. de Boer, Anthonius de Groot, Mark C. H. Drenos, Fotios Ferguson, Jane Fox, Caroline S. Furlong, Clement E. Gibson, Quince Gieger, Christian Gilhuijs-Pederson, Lisa A. Glessner, Joseph T. Goel, Anuj Gong, Yan Grant, Struan F. A. Grobbee, Diederick E. Hastie, Claire Humphries, Steve E. Kim, Cecilia E. Kivimaki, Mika Kleber, Marcus Meisinger, Christa Kumari, Meena Langaee, Taimour Y. Lawlor, Debbie A. Li, Mingyao Lobmeyer, Maximilian T. Maitland-van der Zee, Anke-Hilse Meijs, Matthijs F. L. Molony, Cliona M. Morrow, David A. Murugesan, Gurunathan Musani, Solomon K. Nelson, Christopher P. Newhouse, Stephen J. O'Connell, Jeffery R. Padmanabhan, Sandosh Palmen, Jutta Patel, Sanjey R. Pepine, Carl J. Pettinger, Mary Price, Thomas S. Rafelt, Suzanne Ranchalis, Jane Rasheed, Asif Rosenthal, Elisabeth Ruczinski, Ingo Shah, Sonia Shen, Haiqing Silbernagel, Guenther Smith, Erin N. Spijkerman, Annemieke W. M. Stanton, Alice Steffes, Michael W. Thorand, Barbara Trip, Mieke van der Harst, Pim van der A, Daphne L. van Iperen, Erik P. A. van Setten, Jessica van Vliet-Ostaptchouk, Jana V. Verweij, Niek Wolffenbuttel, Bruce H. R. Young, Taylor Zafarmand, M. Hadi Zmuda, Joseph M. Boehnke, Michael Altshuler, David McCarthy, Mark Kao, W. H. Linda Pankow, James S. Cappola, Thomas P. Sever, Peter Poulter, Neil Caulfield, Mark Dominiczak, Anna Shields, Denis C. Bhatt, Deepak L. Zhang, Li Curtis, Sean P. Danesh, John Casas, Juan P. van der Schouw, Yvonne T. Onland-Moret, N. Charlotte Doevendans, Pieter A. Dorn, Gerald W., II Farrall, Martin FitzGerald, Garret A. Hamsten, Anders Hegele, Robert Hingorani, Aroon D. Hofker, Marten H. Huggins, Gordon S. Illig, Thomas Jarvik, Gail P. Johnson, Julie A. Klungel, Olaf H. Knowler, William C. Koenig, Wolfgang Maerz, Winfried Meigs, James B. Melander, Olle Munroe, Patricia B. Mitchell, Braxton D. Bielinski, Susan J. Rader, Daniel J. Reilly, Muredach P. Rich, Stephen S. Rotter, Jerome I. Saleheen, Danish Samani, Nilesh J. Schadt, Eric E. Shuldiner, Alan R. Silverstein, Roy Kottke-Marchant, Kandice Talmud, Philippa J. Watkins, Hugh Asselbergs, Folkert W. de Bakker, Paul I. W. McCaffery, Jeanne Wijmenga, Cisca Sabatine, Marc S. Wilson, James G. Reiner, Alex Bowden, Donald W. Hakonarson, Hakon Siscovick, David S. Keating, Brendan J. CA Look AHEAD Res Grp Diagram Consortium ASCOT Investigators PROCARDIS TI Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; COMMON VARIANTS; EUROPEAN AMERICANS; AFRICAN-AMERICANS; BLOOD-PRESSURE; RESOURCE CARE; RISK-FACTORS; SNP ARRAY AB To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups. C1 [Saxena, Richa; Tare, Archana; Voight, Benjamin F.; Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Saxena, Richa; Tare, Archana; Voight, Benjamin F.; Young, Taylor; Altshuler, David; de Bakker, Paul I. W.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Elbers, Clara C.] Univ Penn, Dept Genet, Sch Med, Philadelphia, PA 19104 USA. [Elbers, Clara C.; Bauer, Florianne; Onland-Moret, N. Charlotte; de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Complex Genet Sect, Dept Med Genet, Utrecht, Netherlands. [Elbers, Clara C.; Bauer, Florianne; Grobbee, Diederick E.; van der Schouw, Yvonne T.; Onland-Moret, N. Charlotte; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Guo, Yiran; Almoguera Castillo, Berta; Li, Yun R.; Glessner, Joseph T.; Grant, Struan F. A.; Kim, Cecilia E.; Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp, Ctr Appl Genom, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Guo, Yiran] BGI Shenzhen, Shenzhen 518083, Peoples R China. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Gaunt, Tom R.; Davey-Smith, George; Day, Ian N.; Lawlor, Debbie A.] Univ Bristol, Med Res Council Ctr Causal Anal Translat Epidemio, Dept Social Med, Bristol BS8 2BN, Avon, England. [Mega, Jessica L.; Morrow, David A.; Sabatine, Marc S.] Brigham & Womens Hosp, Div Cardiovasc, Thrombolysis Myocardial Infarct Study Grp, Boston, MA 02115 USA. [Lanktree, Matthew B.; Hegele, Robert] Univ Western Ontario, Dept Biochem, London, ON N6A 5C1, Canada. [Almoguera Castillo, Berta] Fdn Jimenez Diaz, Serv Genet, Inst Invest Sanitaria, Madrid 228040, Spain. [Johnson, Toby; Newhouse, Stephen J.; Caulfield, Mark; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Genome Ctr, London EC1M 6BQ, England. [Johnson, Toby; Newhouse, Stephen J.; Caulfield, Mark; Munroe, Patricia B.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med, London EC1M 6BQ, England. [Bruinenberg, Marcel] Univ Groningen, LifeLines Cohort Study & Biobank, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. [Gilbert-Diamond, Diane] Childrens Environm Hlth & Dis Prevent Ctr Dartmou, Hanover, NH 03755 USA. [Gilbert-Diamond, Diane] Dartmouth Med Sch, Sect Biostat & Epidemiol, Dept Community & Family Med, Hanover, NH 03756 USA. [Rajagopalan, Ramakrishnan; Furlong, Clement E.; Ranchalis, Jane; Rosenthal, Elisabeth; Jarvik, Gail P.] Univ Washington, Dept Med Med Genet, Seattle, WA 98195 USA. [Balasubramanyam, Ashok] Baylor Coll Med, Translat Metab Unit, Div Diabet Endocrinol & Metab, Houston, TX 77030 USA. [Barnard, John; Zhang, Li] Cleveland Clin, Dept Quantitat Hlth Sci, Lerner Res Inst, Cleveland, OH 44195 USA. [Baumert, Jens; Meisinger, Christa; Thorand, Barbara] German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Bhangale, Tushar; Furlong, Clement E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Boehm, Bernhard O.] Cardiol Grp Frankfurt Sachsenhausen, D-60598 Frankfurt, Germany. [Braund, Peter S.; Nelson, Christopher P.; Rafelt, Suzanne; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester LE3 9QP, Leics, England. [Burton, Paul R.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England. [Chandrupatla, Hareesh R.; Ferguson, Jane; Li, Mingyao; Cappola, Thomas P.; Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Clarke, Robert] Clin Trial Serv Unit, Oxford OX3 7LF, England. [Cooper-DeHoff, Rhonda M.; Langaee, Taimour Y.; Johnson, Julie A.] Univ Florida, Dept Pharmacotherapy & Translat Res, Coll Pharm, Gainesville, FL 32610 USA. [Cooper-DeHoff, Rhonda M.; Gong, Yan; Lobmeyer, Maximilian T.; Pepine, Carl J.; Johnson, Julie A.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32610 USA. [Crook, Errol D.] Univ S Alabama, Mobile, AL 36608 USA. [de Boer, Anthonius; de Groot, Mark C. H.; Gilhuijs-Pederson, Lisa A.; Maitland-van der Zee, Anke-Hilse; Klungel, Olaf H.] Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, Fac Sci, Utrecht, Netherlands. [Drenos, Fotios; Humphries, Steve E.; Palmen, Jutta; Talmud, Philippa J.] UCL, Ctr Cardiovasc Genet, Dept Med, London WC1E 6JF, England. [Fox, Caroline S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gibson, Quince; O'Connell, Jeffery R.; Shen, Haiqing; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Gieger, Christian; Illig, Thomas] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Goel, Anuj; McCarthy, Mark; Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Hastie, Claire; Padmanabhan, Sandosh; Dominiczak, Anna] Univ Glasgow, British Heart Fdn Glasgow, Cardiovasc Res Ctr, Div Cardiovasc & Med Sci,Western Infirm, Glasgow G12 8TA, Lanark, Scotland. [Kivimaki, Mika; Casas, Juan P.] UCL, Dept Epidemiol & Publ Hlth, London, England. [Kivimaki, Mika; Kumari, Meena] UCL, Genet Epidemiol Grp, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England. [Kleber, Marcus] LURIC Study, D-79098 Freiburg, Germany. [Kleber, Marcus; Maerz, Winfried] Synlab Ctr Lab Diagnost Heidelberg, D-69037 Heidelberg, Germany. [Meijs, Matthijs F. L.; Zafarmand, M. Hadi; Doevendans, Pieter A.; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands. [Molony, Cliona M.] Rosetta Inpharmat, Dept Genet, Seattle, WA 98109 USA. [Murugesan, Gurunathan] Cleveland Clin, Dept Clin Pathol, Pathol & Lab Med Inst, Cleveland, OH 44106 USA. [Musani, Solomon K.; Wilson, James G.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Patel, Sanjey R.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Pettinger, Mary; Reiner, Alex] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Price, Thomas S.] Kings Coll London, Med Res Council, Social Genet & Dev Psychiat Ctr, Inst Psychiat, London WC2R 2LS, England. [Rasheed, Asif; Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan. [Ruczinski, Ingo] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Shah, Sonia] UCL, Univ Coll Genet Inst, London WC1E 6BT, England. [Silbernagel, Guenther] Univ Tubingen, Div Endocrinol Diabetol Nephrol Vasc Dis & Clin C, Dept Internal Med, D-72074 Tubingen, Germany. [Smith, Erin N.] Scripps Genom Med, La Jolla, CA 92037 USA. [Spijkerman, Annemieke W. M.; van der A, Daphne L.] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Stanton, Alice] Royal Coll Surgeons Ireland, Dublin 2, Ireland. [Steffes, Michael W.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Trip, Mieke] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [van der Harst, Pim; Verweij, Niek] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands. [van der Harst, Pim; Wijmenga, Cisca] Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [van Iperen, Erik P. A.] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [van Setten, Jessica; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [van Vliet-Ostaptchouk, Jana V.] Univ Med Ctr Groningen, Dept Pathol & Med Biol, NL-9713 AV Groningen, Netherlands. [van Vliet-Ostaptchouk, Jana V.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands. [Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands. [Zmuda, Joseph M.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA. [Altshuler, David; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [McCarthy, Mark] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. [Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA. [Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55454 USA. [Sever, Peter; Poulter, Neil] Univ London Imperial Coll Sci Technol & Med, Int Ctr Circulatory Hlth, London W2 1PG, England. [Shields, Denis C.] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Cambridge, MA 02115 USA. [Curtis, Sean P.; Saleheen, Danish] Merck Res Labs, Rahway, NJ 07065 USA. [Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Casas, Juan P.] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England. [Dorn, Gerald W., II; Watkins, Hugh] Washington Univ, Ctr Pharmacogenet, St Louis, MO 63110 USA. [Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, John Radcliffe Hosp, Oxford OX3 9DU, England. [FitzGerald, Garret A.] Univ Penn, Inst Translat Med & Therapeut, Sch Med, Philadelphia, PA 19146 USA. [Hamsten, Anders] Karolinska Inst, Cardiovasc Genet Grp, Atherosclerosis Res Unit, Dept Med Solna, SE-17176 Stockholm, Sweden. [Hingorani, Aroon D.] UCL, Ctr Clin Pharmacol, Dept Med, London WC1E 6JF, England. [Huggins, Gordon S.] Tufts Med Ctr, Ctr Translat Genom, Mol Cardiol Res Inst, Boston, MA 02114 USA. [Huggins, Gordon S.] Tufts Univ, Boston, MA 02114 USA. 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[Silverstein, Roy] Case Western Reserve Univ, Dept Cell Biol, Lerner Res Inst,Dept Mol Med, Cleveland Clin Fdn,Cleveland Clin Lerner Coll Med, Cleveland, OH 44195 USA. [Kottke-Marchant, Kandice] Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44195 USA. [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Div Genet, Brigham & Womens Hosp, Boston, MA 02115 USA. [McCaffery, Jeanne] Brown Univ, Miriam Hosp, Weight Control & Diabet Res Ctr, Providence, RI 02906 USA. [McCaffery, Jeanne] Brown Univ, Warren Alpert Sch Med, Providence, RI 02906 USA. [Bowden, Donald W.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC 27106 USA. [Hakonarson, Hakon; Keating, Brendan J.] Childrens Hosp, Div Human Genet, Abramson Res Ctr, Philadelphia, PA 19104 USA. [Hakonarson, Hakon; Keating, Brendan J.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. RP Saxena, R (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM rsaxena@chgr.mgh.harvard.edu; keatingb@email.chop.edu RI Davey Smith, George/A-7407-2013; Price, Thomas/B-7372-2008; Thorand, Barbara/B-5349-2014; Jarvik, Gail/N-6476-2014; Gaunt, Tom/O-3918-2014; Onland-Moret, N. Charlotte/G-9185-2011; de Groot, Mark/A-9891-2012; Hegele, Robert/G-3301-2011; Bielinski, Suzette/A-2238-2009; Burton, Paul/H-7527-2016; Klungel, Olaf/I-9563-2016; Padmanabhan, Sandosh/S-3963-2016; Verweij, Niek/A-4499-2017; Guo, Yiran/H-4120-2011; Smith, Erin/E-5933-2011; Newhouse, Stephen/C-9330-2011; Wijmenga, Cisca/D-2173-2009; Ferguson, Jane/C-7154-2011; Wolffenbuttel, Bruce/A-8419-2011; Stanton, Alice/F-4697-2012; Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009; Shah, Sonia/N-7547-2013; Meisinger, Christine/B-5358-2014; Grobbee, Diederick/C-7651-2014 OI Lawlor, Debbie A/0000-0002-6793-2262; Pankow, James/0000-0001-7076-483X; Kleber, Marcus/0000-0003-0663-7275; Gieger, Christian/0000-0001-6986-9554; Wijmenga, Cisca/0000-0002-5635-1614; Patel, Sanjay/0000-0002-9142-5172; Kumari, Meena/0000-0001-9716-1035; Verweij, Niek/0000-0002-4303-7685; Meisinger, Christa/0000-0002-9026-6544; Watkins, Hugh/0000-0002-5287-9016; van Iperen, Erik/0000-0001-7107-3168; Mitchell, Braxton/0000-0003-4920-4744; Davey Smith, George/0000-0002-1407-8314; Lanktree, Matthew/0000-0002-5750-6286; Stanton, Alice/0000-0002-4961-165X; van Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Kivimaki, Mika/0000-0002-4699-5627; Talmud, Philippa/0000-0002-5560-1933; Johnson, Toby/0000-0002-5998-3270; Padmanabhan, Sandosh/0000-0003-3869-5808; Humphries, Stephen E/0000-0002-8221-6547; Price, Thomas/0000-0001-7356-2109; Thorand, Barbara/0000-0002-8416-6440; Jarvik, Gail/0000-0002-6710-8708; Gaunt, Tom/0000-0003-0924-3247; de Groot, Mark/0000-0002-5764-5788; Bielinski, Suzette/0000-0002-2905-5430; Guo, Yiran/0000-0002-6549-8589; Newhouse, Stephen/0000-0002-1843-9842; Ferguson, Jane/0000-0001-6896-1025; Wolffenbuttel, Bruce/0000-0001-9262-6921; Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Shah, Sonia/0000-0001-5860-4526; Grobbee, Diederick/0000-0003-4472-4468 FU National Heart, Lung, and Blood Institute; NIDDK NIH [DK089378]; Netherlands Organization for Scientific Research (NWO); Massachusetts Institute of Technology [N01-HC-65226] FX The CARe Consortium wishes to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff, and study participants in creating this resource for biomedical research. The following nine parent studies have contributed parent study data, ancillary study data, and DNA samples through the Broad Institute of Harvard University and the Massachusetts Institute of Technology (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community: the Atherosclerosis Risk in Communities (ARIC) study, the Cardiovascular Health Study (CHS), the Cleveland Family Study (CFS), the Cooperative Study of Sickle Cell Disease (CSSCD), the Coronary Artery Risk Development in Young Adults (CARDIA) study, the Framingham Heart Study (FHS), the Jackson Heart Study OHS), the Multi-Ethnic Study of Atherosclerosis (MESA), and the Sleep Heart Health Study (SHHS). R.S. is partially supported by NIDDK NIH R21 (DK089378). C.C.E is supported by a Rubicon grant from the Netherlands Organization for Scientific Research (NWO). Additional acknowledgements for each cohort are listed in the Supplemental Data. Also see the Supplemental Data for conflict-of-interest disclosures for some of the authors. NR 80 TC 127 Z9 129 U1 1 U2 30 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR 9 PY 2012 VL 90 IS 3 BP 410 EP 425 DI 10.1016/j.ajhg.2011.12.022 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 911ZI UT WOS:000301762800007 PM 22325160 ER PT J AU Lee, JM Gillis, T Mysore, JS Ramos, EM Myers, RH Hayden, MR Morrison, PJ Nance, M Ross, CA Margolis, RL Squitieri, F Griguoli, A Di Donato, S Gomez-Tortosa, E Ayuso, C Suchowersky, O Trent, RJ McCusker, E Novelletto, A Frontali, M Jones, R Ashizawa, T Frank, S Saint-Hilaire, MH Hersch, SM Rosas, HD Lucente, D Harrison, MB Zanko, A Abramson, RK Marder, K Sequeiros, J MacDonald, ME Gusella, JF AF Lee, Jong-Min Gillis, Tammy Mysore, Jayalakshmi Srinidhi Ramos, Eliana Marisa Myers, Richard H. Hayden, Michael R. Morrison, Patrick J. Nance, Martha Ross, Christopher A. Margolis, Russell L. Squitieri, Ferdinando Griguoli, Annamaria Di Donato, Stefano Gomez-Tortosa, Estrella Ayuso, Carmen Suchowersky, Oksana Trent, Ronald J. McCusker, Elizabeth Novelletto, Andrea Frontali, Marina Jones, Randi Ashizawa, Tetsuo Frank, Samuel Saint-Hilaire, Marie-Helene Hersch, Steven M. Rosas, Herminia D. Lucente, Diane Harrison, Madaline B. Zanko, Andrea Abramson, Ruth K. Marder, Karen Sequeiros, Jorge MacDonald, Marcy E. Gusella, James F. TI Common SNP-Based Haplotype Analysis of the 4p16.3 Huntington Disease Gene Region SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID EXPANDED CAG REPEAT; AGE-OF-ONSET; TRINUCLEOTIDE REPEAT; HD; ASSOCIATION; EXPANSION; MODIFIER; LENGTH AB Age at the onset of motor symptoms in Huntington disease (HD) is determined largely by the length of a GAG repeat expansion in HIT but is also influenced by other genetic factors. We tested whether common genetic variation near the mutation site is associated with differences in the distribution of expanded GAG alleles or age at the onset of motor symptoms. To define disease-associated single-nucleotide polymorphisms (SNPs), we compared 4p16.3 SNPs in HD subjects with population controls in a case:control strategy, which revealed that the strongest signals occurred at a great distance from the HD mutation as a result of "synthetic association" with SNP alleles that are of low frequency in population controls. Detailed analysis delineated a prominent ancestral haplotype that accounted for similar to 50% of HD chromosomes and extended to at least 938 kb on about half of these. Together, the seven most abundant haplotypes accounted for similar to 83% of HD chromosomes. Neither the extended shared haplotype nor the individual local HTT haplotypes were associated with altered GAG-repeat length distribution or residual age at the onset of motor symptoms, arguing against modification of these disease features by common cis-regulatory elements. Similarly, the 11 most frequent control haplotypes showed no trans-modifier effect on age at the onset of motor symptoms. Our results argue against common local regulatory variation as a factor influencing HD pathogenesis, suggesting that genetic modifiers be sought elsewhere in the genome. They also indicate that genome-wide association analysis with a small number of cases can be effective for regional localization of genetic defects, even when a founder effect accounts for only a fraction of the disorder. C1 [Lee, Jong-Min; Gillis, Tammy; Mysore, Jayalakshmi Srinidhi; Ramos, Eliana Marisa; Lucente, Diane; MacDonald, Marcy E.; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lee, Jong-Min; MacDonald, Marcy E.; Gusella, James F.] Broad Inst Harvard & Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Ramos, Eliana Marisa; Sequeiros, Jorge] Univ Porto, UnIGENe, Inst Mol & Cell Biol, P-4150180 Oporto, Portugal. [Myers, Richard H.; Frank, Samuel; Saint-Hilaire, Marie-Helene] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Hayden, Michael R.] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada. [Morrison, Patrick J.] Belfast Hlth & Social Care Trust, Reg Med Genet Ctr, Belfast BT9 7AB, Antrim, North Ireland. [Morrison, Patrick J.] Univ Ulster, Coleraine BT52 1SA, Londonderry, North Ireland. [Nance, Martha] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Ross, Christopher A.; Margolis, Russell L.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Squitieri, Ferdinando; Griguoli, Annamaria] Inst Ricovero & Cura Carattere Sci Neuromed, Neurogenet Unit, I-86077 Pozzilli, IS, Italy. [Squitieri, Ferdinando; Griguoli, Annamaria] Inst Ricovero & Cura Carattere Sci Neuromed, Ctr Rare Dis, I-86077 Pozzilli, IS, Italy. [Di Donato, Stefano] Fdn IRCCS, Ist Nazl Neurol C Besta, I-20133 Milan, Italy. [Gomez-Tortosa, Estrella] Fdn Jimenez Diaz, Dept Neurol, E-28040 Madrid, Spain. [Ayuso, Carmen] Fdn Jimenez Diaz, Dept Genet, IIS, CIBERER, E-28040 Madrid, Spain. [Suchowersky, Oksana] Univ Alberta, Dept Med Neurol, Edmonton, AB T6G 2B7, Canada. [Suchowersky, Oksana] Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2B7, Canada. [Trent, Ronald J.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [McCusker, Elizabeth] Westmead Hosp, Dept Neurol, Sydney, NSW 2145, Australia. [Novelletto, Andrea] Univ Tor Vergata, Dept Biol, I-00133 Rome, Italy. [Frontali, Marina] CNR, Ist Farmacol Traslaz, I-00133 Rome, Italy. [Jones, Randi] Emory Univ, Dept Neurol, Atlanta, GA 30329 USA. [Ashizawa, Tetsuo] Univ Florida, Dept Neurol, Gainesville, FL 32610 USA. [Hersch, Steven M.; Rosas, Herminia D.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Harrison, Madaline B.] Univ Virginia, Dept Neurol, Charlottesville, VA 22908 USA. [Zanko, Andrea] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Abramson, Ruth K.] Univ S Carolina, Sch Med, Dept Neuropsychiat & Behav Sci, Columbia, SC 29209 USA. [Marder, Karen] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Sequeiros, Jorge] Univ Porto, Inst Ciencias Biomed Abel Salazar, P-4099003 Oporto, Portugal. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu RI Di Donato, Stefano/B-9717-2012; Ross, Christopher/H-8395-2013; Hayden, Michael/D-8581-2011; OI Hayden, Michael/0000-0001-5159-1419; Saint-Hilaire, Marie-Helene/0000-0002-2355-5979; Sequeiros, Jorge/0000-0002-9846-1037; Myers, Richard/0000-0002-8365-2674; Novelletto, Andrea/0000-0002-1146-7680; Ayuso, Carmen/0000-0002-9242-7065; Squitieri, Ferdinando /0000-0002-7397-1727 FU U.S. National Institutes of Health; National Heart, Lung, and Blood Institute [R01 HL087676]; National Center for Research Resources [U54 RR020278]; National Institute of Neurological Disorders and Stroke [NS16367, NS32765]; CHDI Foundation; Huntington's Disease Society of America's Coalition for the Cure; Fundacao para a Ciencia e a Tecnologia of Portugal [SFRH/BD/44335/2008] FX We thank the HD research participants and their families, who made this work possible; the Harvard Brain Tissue Resource Center; the COHORT Study of the Huntington Study Group; and the Myocardial Infarction Genetics Consortium (MIGen) study, which was funded by grants from the U.S. National Institutes of Health and National Heart, Lung, and Blood Institute's STAMPEED genomics research program (R01 HL087676) and the National Center for Research Resources (U54 RR020278). We also thank investigators anti contributors to the I-ID-MAPS study: Alexandra Durr, Adam Rosenblatt, Luigi Frati, Susan Perlman, P. Michael Conneally, Mary Lou Klimek, Melissa Diggin, Tiffany Hadzi, and Ayana Duckett. This work was supported by grants from the National Institute of Neurological Disorders and Stroke (NS16367) (Huntington's Disease Center Without Walls) and NS32765, the CHDI Foundation, and the Huntington's Disease Society of America's Coalition for the Cure. E.M.R. received a scholarship from the Fundacao para a Ciencia e a Tecnologia of Portugal (SFRH/BD/44335/2008). NR 24 TC 19 Z9 19 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR 9 PY 2012 VL 90 IS 3 BP 434 EP 444 DI 10.1016/j.ajhg.2012.01.005 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 911ZI UT WOS:000301762800009 PM 22387017 ER PT J AU Riazuddin, SA Parker, DS McGlumphy, EJ Oh, EC Iliff, BW Schmedt, T Jurkunas, U Schleif, R Katsanis, N Gottsch, JD AF Riazuddin, S. Amer Parker, David S. McGlumphy, Elyse J. Oh, Edwin C. Iliff, Benjamin W. Schmedt, Thore Jurkunas, Ula Schleif, Robert Katsanis, Nicholas Gottsch, John D. TI Mutations in LOXHD1, a Recessive-Deafness Locus, Cause Dominant Late-Onset Fuchs Corneal Dystrophy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ENDOTHELIAL DYSTROPHY; MISSENSE MUTATIONS; PROTEIN; COL8A2; GENE; COLLAGEN; LINKAGE AB Fuchs corneal dystrophy (FCD) is a genetic disorder of the corneal endothelium and is the most common cause of corneal transplantation in the United States. Previously, we mapped a late-onset FCD locus, FCD2, on chromosome 18q. Here, we present next-generation sequencing of all coding exons in the FCD2 critical interval in a multigenerational pedigree in which FCD segregates as an autosomal-dominant trait. We identified a missense change in LOXHD1, a gene causing progressive hearing loss in humans, as the sole variant capable of explaining the phenotype in this pedigree. We observed LOXHD1 mRNA in cultured human corneal endothelial cells, whereas antibody staining of both human and mouse corneas showed staining in the corneal epithelium and endothelium. Corneal sections of the original proband were stained for LOXHD1 and demonstrated a distinct increase in antibody punctate staining in the endothelium and Descemet membrane; punctate staining was absent from both normal corneas and FCD corneas negative for causal LOXHDI mutations. Subsequent interrogation of a cohort of >200 sporadic affected individuals identified another 15 heterozygous missense mutations that were absent from >800 control chromosomes. Furthermore, in silico analyses predicted that these mutations reside on the surface of the protein and are likely to affect the protein's interface and protein-protein interactions. Finally, expression of the familial LOXHD1 mutant allele as well as two sporadic mutations in cells revealed prominent cytoplasmic aggregates reminiscent of the corneal phenotype. All together, our data implicate rare alleles in LOXHD1 in the pathogenesis of FCD and highlight how different mutations in the same locus can potentially produce diverse phenotypes. C1 [Riazuddin, S. Amer; McGlumphy, Elyse J.; Iliff, Benjamin W.; Gottsch, John D.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Parker, David S.; Oh, Edwin C.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Dept Cell Biol, Durham, NC 27710 USA. [Schmedt, Thore; Jurkunas, Ula] Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Schleif, Robert] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Gottsch, JD (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA. EM igottsch@jhmi.edu RI Katsanis, Nicholas/E-1837-2012; OI Katsanis, Nicholas/0000-0002-2480-0171 FU National Eye Institute [R01 EY016835]; Kwok Research Fund FX We thank all family members for their enthusiastic participation in this study. None of the contributing authors have any financial interest related to this work. We are thankful to Ulrich Mueller for providing the Loxhd1 construct. This study was supported in part by the National Eye Institute grant R01 EY016835 (J.D.G.) and the Kwok Research Fund (J.D.G.). J.D.G. is a distinguished Margaret C. Mosher Professor of Ophthalmology. N.K. is a distinguished Brumley Professor. NR 27 TC 51 Z9 52 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR 9 PY 2012 VL 90 IS 3 BP 533 EP 539 DI 10.1016/j.ajhg.2012.01.013 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 911ZI UT WOS:000301762800020 PM 22341973 ER PT J AU Shi, S Deng, YZ Zhao, JS Ji, XD Shi, J Feng, YX Li, G Li, JJ Zhu, D Koeffler, HP Zhao, Y Xie, D AF Shi, Shuo Deng, Yue-Zhen Zhao, Jiang-Sha Ji, Xiao-Dan Shi, Jun Feng, Yu-Xiong Li, Guo Li, Jing-Jing Zhu, Di Koeffler, H. Phillip Zhao, Yun Xie, Dong TI RACK1 Promotes Non-small-cell Lung Cancer Tumorigenicity through Activating Sonic Hedgehog Signaling Pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; DEVELOPMENTAL PATHWAYS; PATCHED-GLI; CARCINOMA; WNT; PHOSPHORYLATION; EXPRESSION; DROSOPHILA; TRANSDUCTION; REQUIREMENT AB Non-small-cell lung cancer (NSCLC) is a deadly disease due to lack of effective diagnosis biomarker and therapeutic target. Much effort has been made in defining gene defects in NSCLC, but its full molecular pathogenesis remains unexplored. Here, we found RACK1 (receptor of activated kinase 1) was elevated in most NSCLC, and its expression level correlated with key pathological characteristics including tumor differentiation, stage, and metastasis. In addition, RACK1 activated sonic hedgehog signaling pathway by interacting with and activating Smoothened to mediate Gli1-dependent transcription in NSCLC cells. And silencing RACK1 dramatically inhibited in vivo tumor growth and metastasis by blocking the sonic hedgehog signaling pathway. These results suggest that RACK1 represents a new promising diagnosis biomarker and therapeutic target for NSCLC. C1 [Shi, Shuo; Deng, Yue-Zhen; Zhao, Jiang-Sha; Ji, Xiao-Dan; Feng, Yu-Xiong; Li, Guo; Li, Jing-Jing; Xie, Dong] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China. [Shi, Shuo; Deng, Yue-Zhen; Zhao, Jiang-Sha; Ji, Xiao-Dan; Feng, Yu-Xiong; Li, Guo; Li, Jing-Jing; Xie, Dong] Chinese Acad Sci, Grad Sch, Shanghai 200031, Peoples R China. [Shi, Jun] Second Peoples Hosp Zhuhai, Zhuhai 519000, Guangdong, Peoples R China. [Zhu, Di] Dana Farber Canc Inst, Boston, MA 02115 USA. [Koeffler, H. Phillip] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 119077, Singapore. [Zhao, Yun] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Mol Cell Biol, Shanghai 200031, Peoples R China. RP Xie, D (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Mol Oncol Lab, 294 Tai Yuan Rd, Shanghai 200031, Peoples R China. EM dxie@sibs.ac.cn FU National Basic Research Program of China [2010CB912102]; Ministry of Science and Technology [2012ZX10002009-017]; National Natural Science Foundation of China [30930023, 90813023, Y239X31111, 81021002, 31100551, 81070325]; National Natural Science Funds for Distinguished Young Scholar [30725010]; Nature Science Foundation of China-Guangdong [U0932001] FX This work was supported by National Basic Research Program of China Grant 2010CB912102, Ministry of Science and Technology Key Program 2012ZX10002009-017, National Natural Science Foundation of China 30930023, 90813023, Y239X31111, 81021002, 31100551, 81021002, and 81070325, National Natural Science Funds for Distinguished Young Scholar Grant 30725010, and Nature Science Foundation of China-Guangdong Joint Fund U0932001. NR 54 TC 29 Z9 33 U1 0 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 9 PY 2012 VL 287 IS 11 BP 7845 EP 7858 DI 10.1074/jbc.M111.315416 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 906MN UT WOS:000301349400002 PM 22262830 ER PT J AU Kim, WJ Rivera, MN Coffman, EJ Haber, DA AF Kim, Woo Jae Rivera, Miguel N. Coffman, Erik J. Haber, Daniel A. TI The WTX Tumor Suppressor Enhances p53 Acetylation by CBP/p300 SO MOLECULAR CELL LA English DT Article ID WILMS-TUMOR; TRANSCRIPTIONAL COACTIVATORS; FUNCTIONAL INTERACTION; SUMO MODIFICATION; GENE-MUTATIONS; CELL-GROWTH; DNA-BINDING; IN-VITRO; ADENOVIRUS; PROTEIN AB WTX encodes a tumor suppressor, frequently inactivated in Wilms tumor, with both plasma membrane and nuclear localization. WTX has been implicated in beta-catenin turnover, but its effect on nuclear proteins is unknown. We report an interaction between WTX and p53, derived from the unexpected observation of WTX, p53, and E1B 55K colocalization within the characteristic cytoplasmic body of adenovirus-transformed kidney cells. In other cells without adenovirus expression, the C-terminal domain of WTX binds to the DNA-binding domain of p53, enhances its binding to CBP, and increases CBP/p300-mediated acetylation of p53 at Lys 373/382. WTX knockdown accelerates CBP/p300 protein turnover and attenuates this modification of p53. In p53-reconstitution experiments, cell-cycle arrest, apoptosis, and p53 target-gene expression are suppressed by depletion of WTX. Together, these results suggest that WTX modulates p53 function, in part through regulation of its activator CBP/p300. C1 [Kim, Woo Jae; Rivera, Miguel N.; Coffman, Erik J.; Haber, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Rivera, Miguel N.; Coffman, Erik J.] Harvard Univ, Dept Pathol, Sch Med, Charlestown, MA 02129 USA. [Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu FU NIH [5R37CA058596, P50CA101942, T32CA009216]; NIDDK; Burroughs Wellcome Fund; HHMI FX This work was supported by NIH 5R37CA058596, P50CA101942, HHMI (D.A.H.); NIH T32CA009216 (W.J.K.); NIDDK; the Burroughs Wellcome Fund; and HHMI (M.N.R.). The authors would like to thank Nick Dyson, Shyamala Maheswaran, and Ho-June Lee for helpful discussions and critical comments. We are grateful to Anders Naar and Joshua Black for providing reagents. NR 55 TC 21 Z9 22 U1 3 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 9 PY 2012 VL 45 IS 5 BP 587 EP 597 DI 10.1016/j.molcel.2011.12.025 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 908BN UT WOS:000301465500004 PM 22285752 ER PT J AU Kriesel, JD Hobbs, MR Jones, BB Milash, B Nagra, RM Fischer, KF AF Kriesel, John D. Hobbs, Maurine R. Jones, Brandt B. Milash, Brett Nagra, Rashed M. Fischer, Kael F. TI Deep Sequencing for the Detection of Virus-Like Sequences in the Brains of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain SO PLOS ONE LA English DT Article ID HEPATITIS-G-VIRUS; C/HEPATITIS-G VIRUS; A-E HEPATITIS; MOLECULAR-CLONING; BLOOD-DONORS; INFECTION; PREVALENCE; DISEASE; GENOME; TRANSMISSION AB Multiple sclerosis (MS) is a demyelinating disease of unknown origin that affects the central nervous system of an estimated 400,000 Americans. GBV-C or hepatitis G is a flavivirus that is found in the serum of 1-2% of blood donors. It was originally associated with hepatitis, but is now believed to be a relatively non-pathogenic lymphotropic virus. Fifty frozen specimens from the brains of deceased persons affected by MS were obtained along with 15 normal control brain specimens. RNA was extracted and ribosomal RNAs were depleted before sequencing on the Illumina GAII. These 36 bp reads were compared with a non-redundant database derived from the 600,000+ viral sequences in GenBank organized into 4080 taxa. An individual read successfully aligned to the viral database was considered to be a "hit''. Normalized MS specimen hit rates for each viral taxon were compared to the distribution of hits in the normal controls. Seventeen MS and 11 control brain extracts were sequenced, yielding 4-10 million sequences ("reads'') each. Over-representation of sequence from at least one of 12 viral taxa was observed in 7 of the 17 MS samples. Sequences resembling other viruses previously implicated in the pathogenesis of MS were not significantly enriched in any of the diseased brain specimens. Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. GBV-C in this brain specimen was confirmed by specific amplification in this single MS brain specimen, but not in the 30 other MS brain samples available. The entire 9.4 kb sequence of this GBV-C isolate is reported here. This study shows the feasibility of deep sequencing for the detection of occult viral infections in the brains of deceased persons with MS. The first isolation of GBV-C from human brain is reported here. C1 [Kriesel, John D.; Hobbs, Maurine R.; Jones, Brandt B.] Univ Utah, Dept Internal Med, Div Infect Dis, Salt Lake City, UT 84112 USA. [Milash, Brett] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Nagra, Rashed M.] W Los Angeles VA Med Ctr, Human Brain & Spinal Fluid Resource Ctr, Los Angeles, CA USA. [Fischer, Kael F.] ARUP Labs, Salt Lake City, UT USA. [Fischer, Kael F.] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA. RP Kriesel, JD (reprint author), Univ Utah, Dept Internal Med, Div Infect Dis, Salt Lake City, UT 84112 USA. EM John.Kriesel@hsc.utah.edu RI Fischer, Kael/F-7756-2015 OI Fischer, Kael/0000-0002-7547-330X FU National Multiple Sclerosis Society FX This investigation was supported by grants from the National Multiple Sclerosis Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 10 Z9 11 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 8 PY 2012 VL 7 IS 3 AR e31886 DI 10.1371/journal.pone.0031886 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 929KT UT WOS:000303062000003 PM 22412845 ER PT J AU Uthamalingam, S Sidhu, MS Gurm, GS Yasuda, T Francis, S Scott, J Gregory, SA AF Uthamalingam, Shanmugam Sidhu, Manavjot S. Gurm, Gagandeep S. Yasuda, Tsunehiro Francis, Sanjeev Scott, James Gregory, Shawn A. TI Male breast uptake of 99m-Tc sestamibi in myocardial perfusion imaging SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Letter DE Male breast; 99m-Tc sestamibi; Myocardial perfusion imaging ID NONCARDIAC FINDINGS; CANCER C1 [Uthamalingam, Shanmugam; Sidhu, Manavjot S.; Francis, Sanjeev] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Uthamalingam, Shanmugam; Sidhu, Manavjot S.; Gurm, Gagandeep S.; Yasuda, Tsunehiro; Francis, Sanjeev; Gregory, Shawn A.] Harvard Univ, Sch Med, Boston, MA USA. [Gurm, Gagandeep S.; Yasuda, Tsunehiro; Francis, Sanjeev; Gregory, Shawn A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Yasuda, Tsunehiro; Scott, James] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. RP Sidhu, MS (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM msidhu1@partners.org NR 9 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAR 8 PY 2012 VL 155 IS 2 BP E22 EP E23 DI 10.1016/j.ijcard.2011.06.080 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 891RG UT WOS:000300233700002 PM 21741712 ER PT J AU Graff, J Rei, D Guan, JS Wang, WY Seo, J Hennig, KM Nieland, TJF Fass, DM Kao, PF Kahn, M Su, SC Samiei, A Joseph, N Haggarty, SJ Delalle, I Tsai, LH AF Graeff, Johannes Rei, Damien Guan, Ji-Song Wang, Wen-Yuan Seo, Jinsoo Hennig, Krista M. Nieland, Thomas J. F. Fass, Daniel M. Kao, Patricia F. Kahn, Martin Su, Susan C. Samiei, Alireza Joseph, Nadine Haggarty, Stephen J. Delalle, Ivana Tsai, Li-Huei TI An epigenetic blockade of cognitive functions in the neurodegenerating brain SO NATURE LA English DT Article ID LONG-TERM-MEMORY; ALZHEIMERS-DISEASE; SYNAPTIC PLASTICITY; CLINICAL-IMPLICATIONS; TRANSGENIC MICE; REMOTE MEMORIES; CDK5; PHOSPHORYLATION; EXPRESSION; CHROMATIN AB Cognitive decline is a debilitating feature of most neurodegenerative diseases of the central nervous system, including Alzheimer's disease(1). The causes leading to such impairment are only poorly understood and effective treatments are slow to emerge(2). Here we show that cognitive capacities in the neurodegenerating brain are constrained by an epigenetic blockade of gene transcription that is potentially reversible. This blockade is mediated by histone deacetylase 2, which is increased by Alzheimer's-disease-related neurotoxic insults in vitro, in two mouse models of neurodegeneration and in patients with Alzheimer's disease. Histone deacetylase 2 associates with and reduces the histone acetylation of genes important for learning and memory, which show a concomitant decrease in expression. Importantly, reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of these genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments. These findings advocate for the development of selective inhibitors of histone deacetylase 2 and suggest that cognitive capacities following neurodegeneration are not entirely lost, but merely impaired by this epigenetic blockade. C1 [Graeff, Johannes; Rei, Damien; Guan, Ji-Song; Wang, Wen-Yuan; Seo, Jinsoo; Kahn, Martin; Su, Susan C.; Samiei, Alireza; Joseph, Nadine; Tsai, Li-Huei] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Graeff, Johannes; Rei, Damien; Guan, Ji-Song; Wang, Wen-Yuan; Seo, Jinsoo; Su, Susan C.; Joseph, Nadine; Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Graeff, Johannes; Guan, Ji-Song; Wang, Wen-Yuan; Hennig, Krista M.; Nieland, Thomas J. F.; Fass, Daniel M.; Joseph, Nadine; Haggarty, Stephen J.; Tsai, Li-Huei] Broad Inst Harvard Univ & Massachusetts Inst Tech, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Hennig, Krista M.; Fass, Daniel M.; Haggarty, Stephen J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kao, Patricia F.; Delalle, Ivana] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. RP Tsai, LH (reprint author), MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, E25-618, Cambridge, MA 02139 USA. EM lhtsai@mit.edu OI Graff, Johannes/0000-0002-3219-3578; Guan, Ji-Song /0000-0001-5219-0289; Haggarty, Stephen J./0000-0002-7872-168X FU Stanley Medical Research Institution; National Institutes of Health/National Institute on Drug Abuse [RO1DA028301]; National Institutes of Health/National Institute of Neurological Disorders and Stroke [RO1NS078839]; Bard Richmond fellowship; Swiss National Science Foundation; Simons Foundation; Theodor und Ida Herzog-Egli foundation FX We thank A. Mungenast, S. Jemielity, R. Madabushi, F. Calderon de Anda and M. Horn for reading the manuscript, A. M. for manuscript editing, M. Eichler for mouse colony maintenance, K. Fitch for sectioning the human brain samples and M. H. for quantification of Fig. 2a. This work was partly supported by the Stanley Medical Research Institution (to S.J.H. and L.-H.T.), National Institutes of Health/National Institute on Drug Abuse (RO1DA028301, to S.J.H.) and National Institutes of Health/National Institute of Neurological Disorders and Stroke (RO1NS078839, to L.-H.T.). J.G. was supported by a Bard Richmond fellowship and by the Swiss National Science Foundation, W.Y.W. by the Simons Foundation and M.K. by the Theodor und Ida Herzog-Egli foundation. L.-H.T. is an investigator of the Howard Hughes Medical Institute. NR 38 TC 268 Z9 279 U1 8 U2 96 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 8 PY 2012 VL 483 IS 7388 BP 222 EP U123 DI 10.1038/nature10849 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904DT UT WOS:000301174900041 PM 22388814 ER PT J AU Jiang, XD Clark, RA Liu, LZ Wagers, AJ Fuhlbrigge, RC Kupper, TS AF Jiang, Xiaodong Clark, Rachael A. Liu, Luzheng Wagers, Amy J. Fuhlbrigge, Robert C. Kupper, Thomas S. TI Skin infection generates non-migratory memory CD8(+) T-RM cells providing global skin immunity SO NATURE LA English DT Article ID DERMAL MICROVESSELS; NONLYMPHOID TISSUE; VIRAL-INFECTION; MIGRATION; TRAFFICKING; EFFECTOR; RESIDENT; HETEROGENEITY; IMMUNIZATION; ACTIVATION AB Protective T-cell memory has long been thought to reside in blood and lymph nodes, but recently the concept of immune memory in peripheral tissues mediated by resident memory T (T-RM) cells has been proposed(1-5). Here we show in mice that localized vaccinia virus (VACV) skin infection generates long-lived non-recirculating CD8(+) skin T-RM cells that reside within the entire skin. These skin T-RM cells are potent effector cells, and are superior to circulating central memory T (T-CM) cells at providing rapid long-term protection against cutaneous re-infection. We find that CD8(+) T cells are rapidly recruited to skin after acute VACV infection. CD8(+) T-cell recruitment to skin is independent of CD4(+) T cells and interferon-c, but requires the expression of E-and P-selectin ligands by CD8(+) T cells. Using parabiotic mice, we further show that circulating CD8(+) T-CM and CD8(+) skin T-RM cells are both generated after skin infection; however, CD8(+) T-CM cells recirculate between blood and lymph nodes whereas T-RM cells remain in the skin. Cutaneous CD8(+) T-RM cells produce effector cytokines and persist for at least 6 months after infection. Mice with CD8(+) skin T-RM cells rapidly cleared a subsequent re-infection with VACV whereas mice with circulating T-CM but no skin T-RM cells showed greatly impaired viral clearance, indicating that T-RM cells provide superior protection. Finally, we show that T-RM cells generated as a result of localized VACV skin infection reside not only in the site of infection, but also populate the entire skin surface and remain present for many months. Repeated re-infections lead to progressive accumulation of highly protective T-RM cells in non-involved skin. These findings have important implications for our understanding of protective immune memory at epithelial interfaces with the environment, and suggest novel strategies for vaccines that protect against tissue tropic organisms. C1 [Jiang, Xiaodong; Clark, Rachael A.; Liu, Luzheng; Fuhlbrigge, Robert C.; Kupper, Thomas S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Jiang, Xiaodong; Clark, Rachael A.; Liu, Luzheng; Fuhlbrigge, Robert C.; Kupper, Thomas S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. [Wagers, Amy J.] Harvard Univ, Howard Hughes Med Inst, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst,Joslin Diabet Ctr, Boston, MA 02115 USA. RP Kupper, TS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. EM tkupper@partners.org FU National Institutes of Health (NIH) [R01AI041707, R37AI025082, TR01AI097128] FX We thank T. Tian, R. Purwar and Q. Zhan for technical assistance. We thank J. J. Campbell for discussion of the project. This work was supported by National Institutes of Health (NIH) grants R01AI041707, R37AI025082 and TR01AI097128 to T.S.K. NR 30 TC 241 Z9 245 U1 2 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 8 PY 2012 VL 483 IS 7388 BP 227 EP U129 DI 10.1038/nature10851 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904DT UT WOS:000301174900042 PM 22388819 ER PT J AU Aaron, HJ Frakt, AB AF Aaron, Henry J. Frakt, Austin B. TI Why Now Is Not the Time for Premium Support SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Aaron, Henry J.] Brookings Inst, Washington, DC 20036 USA. [Frakt, Austin B.] Boston Univ, Sch Med, Dept Vet Affairs, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Frakt, Austin B.] Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Aaron, HJ (reprint author), Brookings Inst, Washington, DC 20036 USA. NR 5 TC 8 Z9 8 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 8 PY 2012 VL 366 IS 10 BP 877 EP 879 DI 10.1056/NEJMp1200448 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 904CY UT WOS:000301172500003 PM 22276779 ER PT J AU Whyte, MP Greenberg, CR Salman, NJ Bober, MB McAlister, WH Wenkert, D Van Sickle, BJ Simmons, JH Edgar, TS Bauer, ML Hamdan, MA Bishop, N Lutz, RE McGinn, M Craig, S Moore, JN Taylor, JW Cleveland, RH Cranley, WR Lim, R Thacher, TD Mayhew, JE Downs, M Millan, JL Skrinar, AM Crine, P Landy, H AF Whyte, Michael P. Greenberg, Cheryl R. Salman, Nada J. Bober, Michael B. McAlister, William H. Wenkert, Deborah Van Sickle, Bradley J. Simmons, Jill H. Edgar, Terence S. Bauer, Martin L. Hamdan, Mohamed A. Bishop, Nick Lutz, Richard E. McGinn, Mairead Craig, Stanley Moore, Jean N. Taylor, John W. Cleveland, Robert H. Cranley, William R. Lim, Ruth Thacher, Tom D. Mayhew, Jill E. Downs, Matthew Millan, Jose Luis Skrinar, Alison M. Crine, Philippe Landy, Hal TI Enzyme-Replacement Therapy in Life-Threatening Hypophosphatasia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONSPECIFIC ALKALINE-PHOSPHATASE; INFANTILE HYPOPHOSPHATASIA; MURINE HYPOPHOSPHATASIA; INTRAVENOUS-INFUSION; BONE; DISEASE; GENE; PYRIDOXAL-5'-PHOSPHATE; TRANSPLANTATION; MINERALIZATION AB BACKGROUND Hypophosphatasia results from mutations in the gene for the tissue-nonspecific isozyme of alkaline phosphatase (TNSALP). Inorganic pyrophosphate accumulates extracellularly, leading to rickets or osteomalacia. Severely affected babies often die from respiratory insufficiency due to progressive chest deformity or have persistent bone disease. There is no approved medical therapy. ENB-0040 is a bone-targeted, recombinant human TNSALP that prevents the manifestations of hypophosphatasia in Tnsalp knockout mice. METHODS We enrolled infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia in a multinational, open-label study of treatment with ENB-0040. The primary objective was the healing of rickets, as assessed by means of radiographic scales. Motor and cognitive development, respiratory function, and safety were evaluated, as well as the pharmacokinetics and pharmacodynamics of ENB-0040. RESULTS Of the 11 patients recruited, 10 completed 6 months of therapy; 9 completed 1 year. Healing of rickets at 6 months in 9 patients was accompanied by improvement in developmental milestones and pulmonary function. Elevated plasma levels of the TNSALP substrates inorganic pyrophosphate and pyridoxal 5'-phosphate diminished. Increases in serum parathyroid hormone accompanied skeletal healing, often necessitating dietary calcium supplementation. There was no evidence of hypocalcemia, ectopic calcification, or definite drug-related serious adverse events. Low titers of anti-ENB-0040 antibodies developed in four patients, with no evident clinical, biochemical, or autoimmune abnormalities at 48 weeks of treatment. CONCLUSIONS ENB-0040, an enzyme-replacement therapy, was associated with improved findings on skeletal radiographs and improved pulmonary and physical function in infants and young children with life-threatening hypophosphatasia. (Funded by Enobia Pharma and Shriners Hospitals for Children; ClinicalTrials.gov number, NCT00744042.) C1 [Whyte, Michael P.; Wenkert, Deborah] Shriners Hosp Children, Ctr Metab Bone Dis & Mol Res, St Louis, MO 63131 USA. [Whyte, Michael P.] Washington Univ, Sch Med, Div Bone & Mineral Dis, Barnes Jewish Hosp, St Louis, MO 63130 USA. [McAlister, William H.] Washington Univ, Sch Med, St Louis Childrens Hosp, Mallinckrodt Inst Radiol, St Louis, MO 63130 USA. [Greenberg, Cheryl R.] Univ Manitoba, Winnipeg, MB, Canada. [Greenberg, Cheryl R.] Winnipeg Reg Hlth Author, Winnipeg, MB, Canada. [Salman, Nada J.; Hamdan, Mohamed A.] Tawam Hosp, Al Ain, U Arab Emirates. [Bober, Michael B.] Alfred I Dupont Hosp Children, Wilmington, DE USA. [Van Sickle, Bradley J.; Simmons, Jill H.] Vanderbilt Childrens Hosp, Nashville, TN USA. [Edgar, Terence S.; Taylor, John W.] Prevea Hlth Clin, Green Bay, WI USA. [Taylor, John W.] St Vincents Hosp, Green Bay, WI USA. [Bauer, Martin L.] Univ Arkansas Med Sci, Coll Med, Little Rock, AR 72205 USA. [Bishop, Nick] Sheffield Childrens Hosp, Sheffield, S Yorkshire, England. [McGinn, Mairead; Craig, Stanley] Royal Belfast Hosp Sick Children, Belfast, Antrim, North Ireland. [Lutz, Richard E.] Univ Nebraska Med Ctr, Omaha, NE USA. [Moore, Jean N.] St Johns Hosp, Springfield, MO USA. [Cleveland, Robert H.] Childrens Hosp, Boston, MA 02115 USA. [Cranley, William R.] Boston Med Ctr, Boston, MA USA. [Lim, Ruth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thacher, Tom D.] Mayo Clin, Rochester, MN USA. [Mayhew, Jill E.; Skrinar, Alison M.; Crine, Philippe; Landy, Hal] Enobia Pharma, Montreal, PQ, Canada. [Downs, Matthew] Stat Collaborat, Washington, DC USA. [Millan, Jose Luis] Sanford Burnham Med Res Inst, La Jolla, CA USA. RP Whyte, MP (reprint author), Shriners Hosp Children, Ctr Metab Bone Dis & Mol Res, 2001 S Lindbergh Blvd, St Louis, MO 63131 USA. EM mwhyte@shrinenet.org OI Bober, Michael/0000-0002-6178-1264 FU Enobia Pharma Hospital for Children; Shriners Hospital for Children FX Supported by Enobia Pharma and Shriners Hospitals for Children. NR 40 TC 118 Z9 122 U1 4 U2 25 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 8 PY 2012 VL 366 IS 10 BP 904 EP 913 DI 10.1056/NEJMoa1106173 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 904CY UT WOS:000301172500007 PM 22397652 ER PT J AU Colao, A Petersenn, S Newell-Price, J Findling, JW Gu, F Maldonado, M Schoenherr, U Mills, D Salgado, LR Biller, BMK AF Colao, Annamaria Petersenn, Stephan Newell-Price, John Findling, James W. Gu, Feng Maldonado, Mario Schoenherr, Ulrike Mills, David Salgado, Luiz Roberto Biller, Beverly M. K. CA Pasireotide B2305 Study Grp TI A 12-Month Phase 3 Study of Pasireotide in Cushing's Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONSENSUS STATEMENT; CABERGOLINE; SOM230; SECRETION; ADENOMAS; RELEASE AB BACKGROUND Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. METHODS In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 mu g (82 patients) or 900 mu g (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 mu g twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. RESULTS Twelve of the 82 patients in the 600-mu g group and 21 of the 80 patients in the 900-mu g group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose- lowering medication was initiated in 74 of 162 patients. CONCLUSIONS The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropinsecreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.) C1 [Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Neuroendocrine Clin Ctr, Boston, MA 02459 USA. [Colao, Annamaria] Univ Naples Federico 2, Endocrinol Sect, Dept Mol & Clin Endocrinol & Oncol, Naples, Italy. [Petersenn, Stephan] ENDOC Ctr Endocrine Tumors, Hamburg, Germany. [Petersenn, Stephan] Univ Duisburg Essen, Fac Med, Essen, Germany. [Newell-Price, John] Univ Sheffield, Dept Human Metab, Sheffield, S Yorkshire, England. [Findling, James W.] Med Coll Wisconsin, Div Endocrinol Metab & Clin Nutr, Milwaukee, WI 53226 USA. [Gu, Feng] Beijing Union Med Coll Hosp, Minist Hlth, Key Lab Endocrinol, Dept Endocrinol, Beijing, Peoples R China. [Maldonado, Mario; Schoenherr, Ulrike; Mills, David] Novartis Pharmaceut, Oncol Business Unit, Clin Dev, Basel, Switzerland. [Salgado, Luiz Roberto] Univ Sao Paulo, Sch Med, Hosp Clin, Div Gen Internal Med, Sao Paulo, Brazil. RP Biller, BMK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Neuroendocrine Clin Ctr, 55 Fruit St,Bulfinch 457B, Boston, MA 02459 USA. EM bbiller@partners.org RI Webb, Susan/C-7294-2008; IBIS, ENDOCRINAS/P-3831-2015; OI Brue, Thierry/0000-0001-8482-6691; Carvalho, Davide/0000-0002-3156-3741 FU Novartis Pharma FX Supported by Novartis Pharma. NR 20 TC 213 Z9 224 U1 4 U2 24 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 8 PY 2012 VL 366 IS 10 BP 914 EP 924 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 904CY UT WOS:000301172500008 PM 22397653 ER PT J AU David, WS Chad, DA Kambadakone, A Hedley-Whyte, ET AF David, William S. Chad, David A. Kambadakone, Avinash Hedley-Whyte, E. Tessa TI Case 7-2012: A 79-Year-Old Man with Pain and Weakness in the Legs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MEDIATED NECROTIZING MYOPATHY; 000 STATIN USERS; THERAPY; RHABDOMYOLYSIS; ROSUVASTATIN; SAFETY C1 [David, William S.; Chad, David A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kambadakone, Avinash] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hedley-Whyte, E. Tessa] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [David, William S.; Chad, David A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Kambadakone, Avinash] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hedley-Whyte, E. Tessa] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP David, WS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 12 TC 2 Z9 3 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 8 PY 2012 VL 366 IS 10 BP 944 EP 954 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 904CY UT WOS:000301172500013 PM 22397657 ER PT J AU Koreth, J Ritz, J Soiffer, RJ AF Koreth, John Ritz, Jerome Soiffer, Robert J. TI Regulatory T Cells in Graft-versus-Host Disease REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Koreth, John; Ritz, Jerome; Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Koreth, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM john_koreth@dfci.harvard.edu NR 4 TC 0 Z9 0 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 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 8 PY 2012 VL 366 IS 10 BP 963 EP 963 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 904CY UT WOS:000301172500019 ER PT J AU Roberts, DJ Celi, AC Riley, LE Onderdonk, AB Boyd, TK Johnson, LC Lieberman, E AF Roberts, Drucilla J. Celi, Ann C. Riley, Laura E. Onderdonk, Andrew B. Boyd, Theonia K. Johnson, Lise Carolyn Lieberman, Ellice TI Acute Histologic Chorioamnionitis at Term: Nearly Always Noninfectious SO PLOS ONE LA English DT Article ID ACUTE PLACENTAL INFLAMMATION; RECEPTOR ANTAGONIST; EPIDURAL ANALGESIA; INFECTION; LABOR; PATTERNS; DELIVERY; FEVER; BIRTH; CYTOKINES AB Background: The link between histologic acute chorioamnionitis and infection is well established in preterm deliveries, but less well-studied in term pregnancies, where infection is much less common. Methodology/Principal Findings: We conducted a secondary analysis among 195 low-risk women with term pregnancies enrolled in a randomized trial. Histologic and microbiologic evaluation of placentas included anaerobic and aerobic cultures (including mycoplasma/ureaplasma species) as well as PCR. Infection was defined as >= 1,000 cfu of a single known pathogen or a >= 2 log difference in counts for a known pathogen versus other organisms in a mixed culture. Placental membranes were scored and categorized as: no chorioamnionitis, Grade 1 (subchorionitis and patchy acute chorioamnionitis), or Grade 2 (severe, confluent chorioamnionitis). Grade 1 or grade 2 histologic chorioamnionitis was present in 34% of placentas (67/195), but infection was present in only 4% (8/195). Histologic chorioamnionitis was strongly associated with intrapartum fever >38 degrees C [69% (25/36) fever, 26% (42/159) afebrile, P<.0001]. Fever occurred in 18% (n = 36) of women. Most febrile women [92% (33/36)] had received epidural for pain relief, though the association with fever was present with and without epidural. The association remained significant in a logistic regression controlling for potential confounders (OR = 5.8, 95% CI = 2.2, 15.0). Histologic chorioamnionitis was also associated with elevated serum levels of interleukin-8 (median = 1.3 pg/mL no histologic chorioamnionitis, 1.5 pg/mL Grade 1, 2.1 pg/mL Grade 2, P = 0.05) and interleukin-6 (median levels = 2.2 pg/mL no chorioamnionitis, 5.3 pg/mL Grade 1, 24.5 pg/mL Grade 2, P = 0.02) at admission for delivery as well as higher admission WBC counts (mean = 12,000cells/mm(3) no chorioamnionitis, 13,400cells/mm(3) Grade 1, 15,700cells/mm(3) Grade 2, P = 0.0005). Conclusion/Significance: Our results suggest histologic chorioamnionitis at term most often results from a noninfectious inflammatory process. It was strongly associated with fever, most of which was related to epidural used for pain relief. A more 'activated' maternal immune system at admission was also associated with histologic chorioamnionitis. C1 [Roberts, Drucilla J.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Celi, Ann C.] Harvard Univ, Brigham & Womens Hosp, Div Gen Med, Sch Med, Boston, MA 02115 USA. [Riley, Laura E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. [Onderdonk, Andrew B.] Harvard Univ, Brigham & Womens Hosp, Clin Microbiol Lab, Sch Med, Boston, MA 02115 USA. [Boyd, Theonia K.] Harvard Univ, Childrens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Lieberman, Ellice] Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Sch Med, Boston, MA 02115 USA. [Lieberman, Ellice] Harvard Univ, Brigham & Womens Hosp, Dept Newborn Med, Sch Med, Boston, MA 02115 USA. RP Roberts, DJ (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM elieberman@partners.org FU Maternal Child Health Bureau, Health Resources and Services Administration [R40 MC00248]; National Heart, Lung, and Blood Institute [RO1HL081663] FX This study was funded by the Maternal Child Health Bureau, Health Resources and Services Administration (R40 MC00248). ACC's work on the current manuscript was in part supported by National Heart, Lung, and Blood Institute reentry award RO1HL081663. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 34 Z9 34 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 7 PY 2012 VL 7 IS 3 AR e31819 DI 10.1371/journal.pone.0031819 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 929KK UT WOS:000303060800005 PM 22412842 ER PT J AU Lin, LY Tiemann, KM Li, Y Pinkner, JS Walker, JN Hultgren, SJ Hunstad, DA Wooley, KL AF Lin, Lily Yun Tiemann, Kristin M. Li, Yali Pinkner, Jerome S. Walker, Jennifer N. Hultgren, Scott J. Hunstad, David A. Wooley, Karen L. TI Synthetic Polymer Nanoparticles Conjugated with FimH(A) from E. coli Pili to Emulate the Bacterial Mode of Epithelial Internalization SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID UROPATHOGENIC ESCHERICHIA-COLI; URINARY-TRACT-INFECTION; UROTHELIAL RECEPTOR; UROPLAKIN-IA; ADHESIN FIMH; EPIDEMIOLOGY; BLADDER; VACCINATION; PARTICLE; BINDING AB Amphiphilic block copolymer nanoparticles are conjugated with uropathogenic Escherichia coli type 1 pilus adhesin FimH(A) through amidation chemistry to enable bladder epithelial cell binding and internalization of the nanoparticles in vitro. C1 [Tiemann, Kristin M.; Walker, Jennifer N.; Hunstad, David A.] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Pinkner, Jerome S.; Hultgren, Scott J.; Hunstad, David A.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Pinkner, Jerome S.; Hultgren, Scott J.; Hunstad, David A.] Washington Univ, Sch Med, Ctr Womens Infect Dis Res, St Louis, MO 63110 USA. [Lin, Lily Yun; Wooley, Karen L.] Texas A&M Univ, Dept Chem & Chem Engn, College Stn, TX 77842 USA. [Li, Yali] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Hunstad, DA (reprint author), Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. EM dhunstad@wusth.edu; wooley@chem.tamu.edu RI Wooley, Karen/D-4399-2015; OI Wooley, Karen/0000-0003-4086-384X; Hunstad, David/0000-0002-9848-0975 FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [R01-DK082546]; March of Dimes [5-FY09-105]; Welch Foundation [A-0001] FX We thank W. Beatty for technical imaging expertise. This project has been funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (R01-DK082546), by a March of Dimes Basil O'Connor Award (5-FY09-105), and by the Welch Foundation through the W. T. Doherty-Welch Chair in Chemistry, grant no. A-0001. NR 30 TC 3 Z9 3 U1 1 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 7 PY 2012 VL 134 IS 9 BP 3938 EP 3941 DI 10.1021/ja2091917 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 909GL UT WOS:000301550800002 PM 22360307 ER PT J AU Pihlajamaki, J Lerin, C Kaminska, D Venesmaa, S Itkonen, P Boes, T Floss, T Schroeder, J Dearie, F Crunkhorn, S Burak, F Jimenez-Chillaron, JC Kuulasmaa, T Miettinen, P Park, PJ Nasser, I Zhao, ZW Zhang, ZY Xu, Y Wurst, W Ren, HM Morris, AJ Stamm, S Goldfine, AB Laakso, M Patti, ME AF Pihlajamaeki, Jussi Lerin, Carles Kaminska, Dorota Venesmaa, Sari Itkonen, Paula Boes, Tanner Floss, Thomas Schroeder, Joshua Dearie, Farrell Crunkhorn, Sarah Burak, Furkan Jimenez-Chillaron, Josep C. Kuulasmaa, Tiina Miettinen, Pekka Park, Peter J. Nasser, Imad Zhao, Zhenwen Zhang, Zhaiyi Xu, Yan Wurst, Wolfgang Ren, Hongmei Morris, Andrew J. Stamm, Stefan Goldfine, Allison B. Laakso, Markku Patti, Mary Elizabeth TI SFRS10-A Splicing Factor Gene Reduced in Human Obesity? Response SO CELL METABOLISM LA English DT Letter ID EXPRESSION C1 [Pihlajamaeki, Jussi; Lerin, Carles; Boes, Tanner; Schroeder, Joshua; Dearie, Farrell; Crunkhorn, Sarah; Burak, Furkan; Jimenez-Chillaron, Josep C.; Goldfine, Allison B.; Patti, Mary Elizabeth] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Park, Peter J.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02215 USA. [Nasser, Imad] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Pihlajamaeki, Jussi; Venesmaa, Sari; Itkonen, Paula; Kuulasmaa, Tiina; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio 70211, Finland. [Pihlajamaeki, Jussi; Kaminska, Dorota] Univ Eastern Finland, Dept Clin Nutr, Kuopio 70211, Finland. [Miettinen, Pekka] Univ Eastern Finland, Dept Surg, Kuopio 70211, Finland. [Lerin, Carles] IDIBAPS CIBERDEM, Diabet & Obes Lab, Barcelona 08036, Spain. [Floss, Thomas; Wurst, Wolfgang] Tech Univ Munich, Inst Entwicklungsgenetik, Helmholtz Zentrum Munchen, D-85764 Munich, Neuherberg, Germany. [Zhao, Zhenwen; Xu, Yan] Indiana Univ, Sch Med, Dept Obstet & Gynecol, Indianapolis, IN 46202 USA. [Zhang, Zhaiyi; Ren, Hongmei; Morris, Andrew J.; Stamm, Stefan] Univ Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USA. [Wurst, Wolfgang] MPI Psychiat, D-80804 Munich, Germany. [Wurst, Wolfgang] Tech Univ Weihenstephan, Lehrstuhl Entwicklungsgenetik, Helmholtz Zentrum Munchen, D-80336 Munich, Germany. [Wurst, Wolfgang] LMU, Adolf Butenandt Inst, DZNE Site Munich, D-80336 Munich, Germany. RP Patti, ME (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu FU NIDDK NIH HHS [P30 DK036836, R01 DK062948] NR 7 TC 2 Z9 2 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAR 7 PY 2012 VL 15 IS 3 BP 267 EP 269 DI 10.1016/j.cmet.2012.02.005 PG 3 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 911EZ UT WOS:000301701400002 PM 25960695 ER PT J AU Ohno, H Shinoda, K Spiegelman, BM Kajimura, S AF Ohno, Haruya Shinoda, Kosaku Spiegelman, Bruce M. Kajimura, Shingo TI PPAR gamma agonists Induce a White-to-Brown Fat Conversion through Stabilization of PRDM16 Protein SO CELL METABOLISM LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; ADIPOSE-TISSUE; TRANSCRIPTIONAL CONTROL; ADULT HUMANS; ADIPOCYTE DIFFERENTIATION; OLIGONUCLEOTIDE ARRAYS; INSULIN-RESISTANCE; EXPRESSION; GENE; LIGAND AB Brown adipose tissue dissipates energy through heat and functions as a defense against cold and obesity. PPAR gamma ligands have been shown to induce the browning of white adipocytes; however, the underlying mechanisms remain unclear. Here, we show that PPAR gamma ligands require full agonism to induce a brown fat gene program preferentially in subcutaneous white adipose. These effects require expression of PRDM16, a factor that controls the development of classical brown fat. Depletion of PRDM16 blunts the effects of the PPAR gamma agonist rosiglitazone on the induced brown fat gene program. Conversely, PRDM16 and rosiglitazone synergistically activate the brown fat gene program in vivo. This synergy is tightly associated with an increased accumulation of PRDM16 protein, due in large measure to an increase in the half-life of the protein in agonist treated cells. Identifying compounds that stabilize PRDM16 protein may represent a plausible therapeutic pathway for the treatment of obesity and diabetes. C1 [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Ohno, Haruya; Shinoda, Kosaku; Kajimura, Shingo] Univ Calif San Francisco, UCSF Diabet Ctr, San Francisco, CA 94143 USA. [Ohno, Haruya; Shinoda, Kosaku; Kajimura, Shingo] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu; skajimura@diabetes.ucsf.edu FU NIH [DK31405, DK090861, DK087853]; DERC [NIH P30 DK063720] FX We thank Dr. Patrick Griffin at the Scripps Institute for providing partial PPAR gamma agonists. We are grateful to Dr. Jang-Hyun Choi, Ms. Emi Tomoda, and Ms. Lauren Ruiz for discussion, technical help, and editorial assistance with the manuscript. This work was supported by grants from the NIH to B.M.S. (DK31405 and DK090861) and to S.K. (DK087853). We also acknowledge the DERC grant (NIH P30 DK063720). NR 46 TC 190 Z9 200 U1 4 U2 23 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD MAR 7 PY 2012 VL 15 IS 3 BP 395 EP 404 DI 10.1016/j.cmet.2012.01.019 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 911EZ UT WOS:000301701400019 PM 22405074 ER PT J AU Blankstein, R Hoffmann, U AF Blankstein, Ron Hoffmann, Udo TI Evaluation for Coronary Artery Disease and Medicare Spending SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID COMPUTED-TOMOGRAPHY; ANGIOGRAPHY; CT C1 [Blankstein, Ron] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Blankstein, R (reprint author), Brigham & Womens Hosp, Noninvas Cardiovasc Imaging Program, 75 Francis St, Boston, MA 02115 USA. EM uhoffmann@partners.org NR 5 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 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 7 PY 2012 VL 307 IS 9 BP 911 EP 912 DI 10.1001/jama.307.9.911-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 904CU UT WOS:000301172100011 PM 22396507 ER PT J AU Blinderman, CD Krakauer, EL Solomon, MZ AF Blinderman, Craig D. Krakauer, Eric L. Solomon, Mildred Z. TI Time to Revise the Approach to Determining Cardiopulmonary Resuscitation Status SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CARE C1 [Blinderman, Craig D.] Columbia Univ, Med Ctr, Dept Anesthesiol, New York, NY 10032 USA. [Solomon, Mildred Z.] Harvard Univ, Sch Med, Div Med Eth, Boston, MA USA. [Krakauer, Eric L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Krakauer, Eric L.; Solomon, Mildred Z.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Krakauer, Eric L.] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [Krakauer, Eric L.] Massachusetts Gen Hosp, Optimum Care Comm, Boston, MA 02114 USA. [Solomon, Mildred Z.] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. RP Blinderman, CD (reprint author), Columbia Univ, Med Ctr, Dept Anesthesiol, 622 W 168th St,PH5-530B, New York, NY 10032 USA. EM cdb21@columbia.edu NR 7 TC 32 Z9 32 U1 0 U2 10 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 MAR 7 PY 2012 VL 307 IS 9 BP 917 EP 918 DI 10.1001/jama.2012.236 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 904CU UT WOS:000301172100017 PM 22396511 ER PT J AU Seal, KH Shi, Y Cohen, G Cohen, BE Maguen, S Krebs, EE Neylan, TC AF Seal, Karen H. Shi, Ying Cohen, Gregory Cohen, Beth E. Maguen, Shira Krebs, Erin E. Neylan, Thomas C. TI Association of Mental Health Disorders With Prescription Opioids and High-Risk Opioid Use in US Veterans of Iraq and Afghanistan SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; OPERATIONS ENDURING FREEDOM; VIETNAM COMBAT VETERANS; CHRONIC NONCANCER PAIN; COMORBID CHRONIC PAIN; PRIMARY-CARE PATIENTS; MEDICATION USE; WAR; PTSD; PREVALENCE AB Context Record numbers of Iraq and Afghanistan veterans survive their war injuries and yet continue to experience pain and mental health problems, particularly post-traumatic stress disorder (PTSD). Little is known about the association of mental health disorders and prescription opioid use. Objective To investigate the effect of mental health disorders, particularly PTSD, on risks and adverse clinical outcomes associated with prescription opioid use. Design Retrospective cohort study involving 141 029 Iraq and Afghanistan veterans who received at least 1 non-cancer-related pain diagnosis within 1 year of entering the Department of Veterans Affairs (VA) health care system from October 1, 2005, through December 31, 2010. Main Outcome Measures Independent association of mental health disorders and the prescription of opioids, higher risk opioid use, and adverse clinical outcomes (eg, accidents and overdose) within 1 year of receiving a pain-related diagnosis. Results A total of 15 676 veterans were prescribed opioids within 1 year of their initial pain diagnosis. Compared with 6.5% of veterans without mental health disorders, 17.8% (adjusted relative risk [RR], 2.58; 95% CI, 2.49-2.67) of veterans with PTSD and 11.7% (adjusted RR, 1.74; 95% CI, 1.67-1.82) with other mental health diagnoses but without PTSD were significantly more likely to receive opioids for pain diagnoses. Of those who were prescribed pain medication, veterans with PTSD were more likely than those without mental health disorders to receive higher-dose opioids (22.7% vs 15.9%, adjusted RR, 1.42; 95% CI, 1.31-1.54), receive 2 or more opioids concurrently (19.8% vs 10.7%, adjusted RR, 1.87; 95% CI, 1.70-2.06), receive sedative hypnotics concurrently (40.7% vs 7.6%, adjusted RR, 5.46; 95% CI, 4.91-6.07), or obtain early opioid refills (33.8% vs 20.4%; adjusted RR, 1.64; 95% CI, 1.531.75). Receiving prescription opioids (vs not) was associated with an increased risk of adverse clinical outcomes for all veterans (9.5% vs 4.1%; RR, 2.33; 95% CI, 2.20-2.46), which was most pronounced in veterans with PTSD. Conclusion Among US veterans of Iraq and Afghanistan, mental health diagnoses, especially PTSD, were associated with an increased risk of receiving opioids for pain, high-risk opioid use, and adverse clinical outcomes. JAMA. 2012;307(9):940-947 www.jama.com C1 [Seal, Karen H.] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94121 USA. [Krebs, Erin E.] Indiana Univ Sch Med, Roudebush Vet Affairs Med Ctr, Indianapolis, IN USA. [Krebs, Erin E.] Regenstrief Inst Inc, Indianapolis, IN USA. RP Seal, KH (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Med, 4150 Clement St,POB 111A-1, San Francisco, CA 94121 USA. EM karen.seal@ucsf.edu FU Department of Veterans Affairs (VA), Health Services Research and Development (HSRD) at the San Francisco VA Medical Center; VA HSRD [RCD 06-042, CD2 07-215]; National Institutes of Health, National Heart, Lung, and Blood Institute [K23 HL 094765-01] FX This work was financially supported by the Department of Veterans Affairs (VA), Health Services Research and Development (HSRD) Research Enhancement Award Program at the San Francisco VA Medical Center (Dr Seal), by VA HSRD Career Development Awards RCD 06-042 (Dr Maguen), and CD2 07-215 (Dr Krebs), and grant K23 HL 094765-01 from the National Institutes of Health, National Heart, Lung, and Blood Institute (Dr Cohen). NR 52 TC 135 Z9 135 U1 1 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 MAR 7 PY 2012 VL 307 IS 9 BP 940 EP 947 DI 10.1001/jama.2012.234 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 904CU UT WOS:000301172100022 PM 22396516 ER PT J AU Schomer, DL Lewis, RJ AF Schomer, Donald L. Lewis, Roger J. TI Stopping Seizures Early and the Surgical Epilepsy Trial That Stopped Even Earlier SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CLINICAL-TRIALS; BENEFIT; SURGERY C1 [Schomer, Donald L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Lewis, Roger J.] Harbor UCLA Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA. [Lewis, Roger J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Schomer, DL (reprint author), BIDMC, Clin Neurophysiol Lab, Baker 504,330 Brookline Ave, Boston, MA 02215 USA. EM dschomer@bidmc.harvard.edu NR 21 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 7 PY 2012 VL 307 IS 9 BP 966 EP 968 DI 10.1001/jama.2012.251 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 904CU UT WOS:000301172100026 PM 22396519 ER PT J AU Markmann, JF Kawai, T AF Markmann, James F. Kawai, Tatsuo TI The Quest for Transplantation Tolerance: Have We Finally Sipped from the Cup? SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material ID PREPARATIVE REGIMEN; MIXED CHIMERISM; ALLOGRAFTS C1 [Markmann, James F.; Kawai, Tatsuo] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kawai, T (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM tkawai@partners.org FU NIAID NIH HHS [R01 AI057851] NR 10 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD MAR 7 PY 2012 VL 4 IS 124 AR 124fs5 DI 10.1126/scitranslmed.3003678 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 905UY UT WOS:000301302600001 PM 22399262 ER PT J AU Shi, YC Kirwan, P Smith, J MacLean, G Orkin, SH Livesey, FJ AF Shi, Yichen Kirwan, Peter Smith, James MacLean, Glenn Orkin, Stuart H. Livesey, Frederick J. TI A Human Stem Cell Model of Early Alzheimer's Disease Pathology in Down Syndrome SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID AMYLOID PLAQUE-FORMATION; TRANSGENIC MICE; BETA-PROTEIN; TAU-PROTEIN; BRAIN; CONVERSION; DEMENTIA; GENETICS; DEFECTS; NEURONS AB Human cellular models of Alzheimer's disease (AD) pathogenesis would enable the investigation of candidate pathogenic mechanisms in AD and the testing and developing of new therapeutic strategies. We report the development of AD pathologies in cortical neurons generated from human induced pluripotent stem (iPS) cells derived from patients with Down syndrome. Adults with Down syndrome (caused by trisomy of chromosome 21) develop early-onset AD, probably due to increased expression of a gene on chromosome 21 that encodes the amyloid precursor protein (APP). We found that cortical neurons generated from iPS cells and embryonic stem cells from Down syndrome patients developed AD pathologies over months in culture, rather than years in vivo. These cortical neurons processed the transmembrane APP protein, resulting in secretion of the pathogenic peptide fragment amyloid-beta 42 (A beta 42), which formed insoluble intracellular and extracellular amyloid aggregates. Production of A beta peptides was blocked by a gamma-secretase inhibitor. Finally, hyperphosphorylated tau protein, a pathological hallmark of AD, was found to be localized to cell bodies and dendrites in iPS cell-derived cortical neurons from Down syndrome patients, recapitulating later stages of the AD pathogenic process. C1 [Shi, Yichen; Kirwan, Peter; Smith, James; Livesey, Frederick J.] Univ Cambridge, Gurdon Inst, Cambridge CB2 1QN, England. [Shi, Yichen; Kirwan, Peter; Smith, James; Livesey, Frederick J.] Univ Cambridge, Dept Biochem, Cambridge CB2 1QN, England. [MacLean, Glenn; Orkin, Stuart H.] Childrens Hosp, Howard Hughes Med Inst, Dept Pediat Oncol, Dana Farber Canc Inst,Div Hematol Oncol, Boston, MA 02115 USA. [MacLean, Glenn; Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Livesey, FJ (reprint author), Univ Cambridge, Gurdon Inst, Tennis Court Rd, Cambridge CB2 1QN, England. EM rick@gurdon.cam.ac.uk OI Kirwan, Peter/0000-0003-1446-7544; Smith, James/0000-0001-9131-5849 FU Wellcome Trust; Cancer Research UK; Alzheimer's Research UK FX This research benefits from core support to the Gurdon Institute from the Wellcome Trust and Cancer Research UK and grants to F.J.L. from the Wellcome Trust and Alzheimer's Research UK. NR 38 TC 32 Z9 33 U1 4 U2 46 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 MAR 7 PY 2012 VL 4 IS 124 AR 124ra29 DI 10.1126/scitranslmed.3003771 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 905UY UT WOS:000301302600005 PM 22344463 ER PT J AU Clasie, B Depauw, N Fransen, M Goma, C Panahandeh, HR Seco, J Flanz, JB Kooy, HM AF Clasie, Benjamin Depauw, Nicolas Fransen, Maurice Goma, Carles Panahandeh, Hamid Reza Seco, Joao Flanz, Jacob B. Kooy, Hanne M. TI Golden beam data for proton pencil-beam scanning SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MONTE-CARLO SIMULATIONS; THERAPY; ALGORITHM; DELIVERY; DESIGN; NOZZLE AB Proton, as well as other ion, beams applied by electro-magnetic deflection in pencil-beam scanning (PBS) are minimally perturbed and thus can be quantified a priori by their fundamental interactions in a medium. This a priori quantification permits an optimal reduction of characterizing measurements on a particular PBS delivery system. The combination of a priori quantification and measurements will then suffice to fully describe the physical interactions necessary for treatment planning purposes. We consider, for proton beams, these interactions and derive a 'Golden' beam data set. The Golden beam data set quantifies the pristine Bragg peak depth-dose distribution in terms of primary, multiple Coulomb scatter, and secondary, nuclear scatter, components. The set reduces the required measurements on a PBS delivery system to the measurement of energy spread and initial phase space as a function of energy. The depth doses are described in absolute units of Gy(RBE) mm(2) Gp(-1), where Gp equals 10(9) (giga) protons, thus providing a direct mapping from treatment planning parameters to integrated beam current. We used these Golden beam data on our PBS delivery systems and demonstrated that they yield absolute dosimetry well within clinical tolerance. C1 [Clasie, Benjamin; Depauw, Nicolas; Fransen, Maurice; Goma, Carles; Panahandeh, Hamid Reza; Seco, Joao; Flanz, Jacob B.; Kooy, Hanne M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Clasie, Benjamin; Depauw, Nicolas; Fransen, Maurice; Goma, Carles; Panahandeh, Hamid Reza; Seco, Joao; Flanz, Jacob B.; Kooy, Hanne M.] Harvard Univ, Sch Med, Boston, MA USA. [Fransen, Maurice] Eindhoven Univ Technol, Dept Appl Phys, NL-5600 MB Eindhoven, Netherlands. RP Clasie, B (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM bclasie@partners.org RI Seco, Joao/J-4451-2012; OI Goma, Carles/0000-0003-0336-390X FU Massachusetts General Hospital; La Caixa Foundation Spain FX Funded in part through the Massachusetts General Hospital managed National Cancer Institute federal share program. One of us, CG, was supported by a La Caixa Foundation fellowship, Spain. NR 14 TC 35 Z9 35 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 7 PY 2012 VL 57 IS 5 BP 1147 EP 1158 DI 10.1088/0031-9155/57/5/1147 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 898XL UT WOS:000300775600005 PM 22330090 ER PT J AU Carabe, A Moteabbed, M Depauw, N Schuemann, J Paganetti, H AF Carabe, Alejandro Moteabbed, Maryam Depauw, Nicolas Schuemann, Jan Paganetti, Harald TI Range uncertainty in proton therapy due to variable biological effectiveness SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID LOW-ENERGY PROTONS; LINEAR-QUADRATIC MODEL; HAMSTER V79 CELLS; EFFECTIVENESS RBE; BEAM THERAPY; INACTIVATION; SURVIVAL; VALUES AB Traditionally, dose in proton radiotherapy is prescribed as Gy(RBE) by scaling up the physical dose by 10%. The relative biological effectiveness (RBE) of protons is considered to vary with dose-averaged linear energy transfer (LETd), dose (d) and (alpha/beta)(x). The increase of RBE with depth causes a shift of the falloff of the beam, i.e. a change of the beam range. The magnitude of this shift will depend on dose and (alpha/beta)(x). The aim of this project was to quantify the dependence of the range shift on these parameters. Three double-scattered beams of different ranges incident on a computational phantom consisting of different regions of interest (ROIs) were used. Each ROI was assigned with (alpha/beta)(x) values between 0.5 and 20 Gy. The distribution of LETd within each ROI was obtained from a Monte Carlo simulation. The LETd distribution depends on the beam energy and thus its nominal range. The RBE values within the ROIs were calculated for doses between 1 and 15 Gy using an in-house developed biophysical model. Dose-volume histograms of the RBE-weighted doses were extracted for each ROI for a 'fixed RBE' (RBE = 1.1) and a 'variable RBE' (RBE = f (d, alpha/beta, LETd)), and the percentage difference in range was obtained from the difference of the percentage volumes at the distal 80% of the dose. Range differences in normal tissue ((alpha/beta)(x) = 3 Gy) of the order of 3-2 mm were obtained, respectively, for a shallow (physical range 4.8 cm) and a deep (physical range 12.8 cm) beam, when a dose of 1 Gy normalized to the mid-SOBP was delivered. As the dose increased to 15 Gy, the variable RBE decreases below 1.1 which induces ranges of about 1 mm shorter than those obtained with an RBE of 1.1. The shift in the range of an SOBP when comparing biological dose distributions obtained with a fixed or a variable RBE was quantified as a function of dose, (alpha/beta)(x) and physical range (as a surrogate of the initial beam energy). The shift increases with the physical range but decreases with increasing dose or (alpha/beta)(x). The results of our study allow a quantitative consideration of RBE-caused range uncertainties as a function of treatment site and dose in treatment planning. C1 [Carabe, Alejandro; Moteabbed, Maryam; Depauw, Nicolas; Schuemann, Jan; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Carabe, Alejandro; Moteabbed, Maryam; Depauw, Nicolas; Schuemann, Jan; Paganetti, Harald] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Carabe, Alejandro] Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Carabe, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM a.carabe@uphs.upenn.edu NR 23 TC 53 Z9 53 U1 5 U2 21 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 7 PY 2012 VL 57 IS 5 BP 1159 EP 1172 DI 10.1088/0031-9155/57/5/1159 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 898XL UT WOS:000300775600006 PM 22330133 ER PT J AU Ramakrishnan, J Craft, D Bortfeld, T Tsitsiklis, JN AF Ramakrishnan, Jagdish Craft, David Bortfeld, Thomas Tsitsiklis, John N. TI A dynamic programming approach to adaptive fractionation SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID VARIABLE INTRAFRACTION MOTION; RADIATION-THERAPY; ONLINE MODIFICATION; PROSTATE-CANCER; BY-FRACTION; IMRT; DELIVERY; STRATEGY; IMAGES; TARGET AB We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are as follows: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive fractionation, because it allows us to assess how close to optimal different methods are, and (ii) heuristic methods proposed in this paper are near-optimal, and therefore, can be used to evaluate the best possible benefit of using an adaptive fraction size. The essence of adaptive fractionation is to increase the fraction size when the tumor and organ-at-risk (OAR) are far apart (a 'favorable' anatomy) and to decrease the fraction size when they are close together. Given that a fixed prescribed dose must be delivered to the tumor over the course of the treatment, such an approach results in a lower cumulative dose to the OAR when compared to that resulting from standard fractionation. We first establish a benchmark by using the DP algorithm to solve the problem exactly. In this case, we characterize the structure of an optimal policy, which provides guidance for our choice of heuristics. We develop two intuitive, numerically near-optimal heuristic policies, which could be used for more complex, high-dimensional problems. Furthermore, one of the heuristics requires only a statistic of the motion probability distribution, making it a reasonable method for use in a realistic setting. Numerically, we find that the amount of decrease in dose to the OAR can vary significantly (5-85%) depending on the amount of motion in the anatomy, the number of fractions and the range of fraction sizes allowed. In general, the decrease in dose to the OAR is more pronounced when: (i) we have a high probability of large tumor-OAR distances, (ii) we use many fractions (as in a hyper-fractionated setting) and (iii) we allow large daily fraction size deviations. C1 [Ramakrishnan, Jagdish; Tsitsiklis, John N.] MIT, Lab Informat & Decis Syst, Cambridge, MA 02139 USA. [Craft, David; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Craft, David; Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ramakrishnan, J (reprint author), MIT, Lab Informat & Decis Syst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jagdish@mit.edu; dcraft@partners.org; tbortfeld@partners.org; jnt@mit.edu FU Siemens FX This work was partially supported by Siemens. NR 23 TC 2 Z9 2 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 7 PY 2012 VL 57 IS 5 BP 1203 EP 1216 DI 10.1088/0031-9155/55/5/1203 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 898XL UT WOS:000300775600009 PM 22330328 ER PT J AU St James, S Mishra, P Hacker, F Berbeco, RI Lewis, JH AF St James, Sara Mishra, Pankaj Hacker, Fred Berbeco, Ross I. Lewis, John H. TI Quantifying ITV instabilities arising from 4DCT: a simulation study using patient data SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; LUNG-TUMOR TRACKING; INTENSITY PROJECTION; RESPIRATORY MOTION; TARGET VOLUME; RADIOTHERAPY; CANCER; SIZE AB Treatment planning for patients undergoing radiation therapy is often performed based on four-dimensional computed tomography (4DCT) when respiratory motion is present, as in lung cancer patients. 4DCT is used to define the internal target volume (ITV) that, ideally, incorporates all potential locations of the tumour. In this work, we use the locations of gold fiducial markers implanted in lung tumours of eight patients to represent tumour motion. These fiducial locations are used in a simulation of a four-slice CT scanner to generate the ITV for 10, 20 and 30 mm diameter model tumours. To demonstrate instabilities in the ITV definition based on 4DCT, the ITV calculation was repeated for the same patients for consecutive scan start times, staggered by 1 s. The volumetric difference in the ITV and the per cent of time that the ITV contains in the tumour are both evaluated. The ITV from a single patient was found to vary by 46%-127% for a tumour diameter of 10 mm. The ITV did not cover the entirety of the tumour 11%-74% of the time for a 10 mm tumour diameter. C1 [St James, Sara] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP St James, S (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. EM sara.stjames@gmail.com; jhlewis@lroc.harvard.edu FU NIH [R21CA156068-01A1] FX The authors would like to thank Dr Seiko Nishioka of the Department of Radiology, NTT Hospital, Sapporo, Japan and Hiroki Shirato of the Department of Radiation Medicine, Hokkaido University School of Medicine, Sapporo, Japan for sharing the Hokkaido dataset with them. The authors would also like to thank Dr Mike Makrigiorgos for insightful discussions during the preparation of the manuscript. The work presented here was supported, in part, by NIH R21CA156068-01A1. NR 13 TC 3 Z9 3 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 7 PY 2012 VL 57 IS 5 BP L1 EP L7 DI 10.1088/0031-9155/57/5/L1 PG 7 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 898XL UT WOS:000300775600001 ER PT J AU Zhang, HM Dang, H Kamat, A Yeh, CK Zhang, BX AF Zhang, Hong-Mei Dang, Howard Kamat, Amrita Yeh, Chih-Ko Zhang, Bin-Xian TI Geldanamycin Derivative Ameliorates High Fat Diet-Induced Renal Failure in Diabetes SO PLOS ONE LA English DT Article ID INDUCED INSULIN-RESISTANCE; MITOCHONDRIAL CA2+ EFFLUX; PROXIMAL TUBULAR CELLS; BLOOD-GLUCOSE CONTROL; OXIDATIVE STRESS; MESANGIAL CELLS; MOLECULAR-MECHANISMS; BARDOXOLONE METHYL; SKELETAL-MUSCLE; KIDNEY-FUNCTION AB Diabetic nephropathy is a serious complication of longstanding diabetes and its pathogenesis remains unclear. Oxidative stress may play a critical role in the pathogenesis and progression of diabetic nephropathy. Our previous studies have demonstrated that polyunsaturated fatty acids (PUFA) induce peroxynitrite generation in primary human kidney mesangial cells and heat shock protein 90 beta 1 (hsp90 beta 1) is indispensable for the PUFA action. Here we investigated the effects of high fat diet (HFD) on kidney function and structure of db/db mice, a widely used rodent model of type 2 diabetes. Our results indicated that HFD dramatically increased the 24 h-urine output and worsened albuminuria in db/db mice. Discontinuation of HFD reversed the exacerbated albuminuria but not the increased urine output. Prolonged HFD feeding resulted in early death of db/db mice, which was associated with oliguria and anuria. Treatment with the geldanamycin derivative, 17-(dimethylaminoehtylamino)-17-demethoxygeldanamycin (17-DMAG), an hsp90 inhibitor, preserved kidney function, and ameliorated glomerular and tubular damage by HFD. 17-DMAG also significantly extended survival of the animals and protected them from the high mortality associated with renal failure. The benefit effect of 17-DMAG on renal function and structure was associated with a decreased level of kidney nitrotyrosine and a diminished kidney mitochondrial Ca2+ efflux in HFD-fed db/db mice. These results suggest that hsp90 beta 1 is a potential target for the treatment of nephropathy and renal failure in diabetes. C1 [Zhang, Hong-Mei] Fourth Mil Med Univ, Dept Clin Oncol, Xijing Hosp, Xian 710032, Peoples R China. [Zhang, Hong-Mei; Kamat, Amrita; Zhang, Bin-Xian] Univ Texas San Antonio, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. [Dang, Howard; Yeh, Chih-Ko; Zhang, Bin-Xian] Univ Texas San Antonio, Hlth Sci Ctr, Dept Comprehens Dent, San Antonio, TX USA. [Kamat, Amrita; Yeh, Chih-Ko; Zhang, Bin-Xian] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Zhang, HM (reprint author), Fourth Mil Med Univ, Dept Clin Oncol, Xijing Hosp, Xian 710032, Peoples R China. EM zhangb2@uthscsa.edu FU Mike Hogg Fund; National Institutes of Health (NIH); Department of Veterans Health Care; National Natural Science Foundation of China [30900673]; Natural Science Foundation of Shaanxi Province [SJ08-ZT10] FX This work was supported by the Mike Hogg Fund, National Institutes of Health (NIH), The Department of Veterans Health Care, the National Natural Science Foundation of China (No. 30900673), and Natural Science Foundation of Shaanxi Province(SJ08-ZT10). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 11 Z9 12 U1 1 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 6 PY 2012 VL 7 IS 3 AR e32746 DI 10.1371/journal.pone.0032746 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928XD UT WOS:000303021100027 PM 22412919 ER PT J AU Thombs, BD Coyne, JC Cuijpers, P de Jonge, P Gilbody, S Ioannidis, JPA Johnson, BT Patten, SB Turner, EH Ziegelstein, RC AF Thombs, Brett D. Coyne, James C. Cuijpers, Pim de Jonge, Peter Gilbody, Simon Ioannidis, John P. A. Johnson, Blair T. Patten, Scott B. Turner, Erick H. Ziegelstein, Roy C. TI Rethinking recommendations for screening for depression in primary care SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Article ID CASE-FINDING INSTRUMENTS; ANTIDEPRESSANT TRIALS; NATIONAL PATTERNS; RANDOMIZED-TRIAL; METAANALYSIS; EFFICACY; SEVERITY; OUTCOMES; PUBLICATION; DIAGNOSIS C1 [Thombs, Brett D.] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Thombs, Brett D.] McGill Univ, Dept Med, Montreal, PQ, Canada. [Thombs, Brett D.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada. [Thombs, Brett D.] McGill Univ, Dept Biostat, Montreal, PQ, Canada. [Thombs, Brett D.] McGill Univ, Dept Occupat Hlth, Montreal, PQ, Canada. [Thombs, Brett D.] McGill Univ, Sch Nursing, Montreal, PQ, Canada. McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. [Coyne, James C.] Univ Penn, Sch Med, Behav Oncol Program, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Coyne, James C.] Univ Groningen, Hlth Psychol Sect, Dept Hlth Sci, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. [Cuijpers, Pim] Vrije Univ Amsterdam, Dept Clin Psychol, Amsterdam, Netherlands. [Cuijpers, Pim] Vrije Univ Amsterdam, EMGO Inst, Amsterdam, Netherlands. [de Jonge, Peter] Univ Groningen, Interdisciplinary Ctr Psychiat Epidemiol, Univ Med Ctr, Groningen, Netherlands. [Gilbody, Simon] Univ York, Hull York Med Sch, York YO10 5DD, N Yorkshire, England. Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Inst Clin Res & Hlth Policy Studies, Tufts Med Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Ioannidis, John P. A.] Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA. [Johnson, Blair T.] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Johnson, Blair T.] Univ Connecticut, Ctr Hlth Intervent & Prevent, Storrs, CT USA. [Patten, Scott B.] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Patten, Scott B.] Univ Calgary, Dept Community Hlth Sci, Calgary, AB, Canada. [Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. [Ziegelstein, Roy C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Thombs, BD (reprint author), McGill Univ, Dept Psychiat, Montreal, PQ, Canada. EM brett.thombs@mcgill.ca RI Turner, Erick/A-4848-2008; de Jonge, peter/L-6395-2013; Cuijpers, Pim/G-1703-2013; Patten, Scott/B-4434-2011; OI Turner, Erick/0000-0002-3522-3357; de Jonge, peter/0000-0002-0866-6929; Patten, Scott/0000-0001-9871-4041; Cuijpers, Pim/0000-0001-5497-2743; Thombs, Brett/0000-0002-5644-8432 FU Canadian Institutes of Health Research [MIN 92725]; NCCIH NIH HHS [R24 AT004641, R24AT004641] NR 47 TC 63 Z9 63 U1 1 U2 16 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD MAR 6 PY 2012 VL 184 IS 4 BP 413 EP 418 DI 10.1503/cmaj.111035 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 908BM UT WOS:000301465400009 PM 21930744 ER PT J AU Reynolds, MR Magnuson, EA Wang, KJ Lei, Y Vilain, K Walczak, J Kodali, SK Lasala, JM O'Neill, WW Davidson, CJ Smith, CR Leon, MB Cohen, DJ AF Reynolds, Matthew R. Magnuson, Elizabeth A. Wang, Kaijun Lei, Yang Vilain, Katherine Walczak, Joshua Kodali, Susheel K. Lasala, John M. O'Neill, William W. Davidson, Charles J. Smith, Craig R. Leon, Martin B. Cohen, David J. CA PARTNER Investigators TI Cost-Effectiveness of Transcatheter Aortic Valve Replacement Compared With Standard Care Among Inoperable Patients With Severe Aortic Stenosis Results From the Placement of Aortic Transcatheter Valves (PARTNER) Trial (Cohort B) SO CIRCULATION LA English DT Article DE aortic stenosis; transcatheter valve therapy; cost-effectiveness; clinical trials ID HEART-FAILURE; ECONOMIC-EVALUATION; HEALTH; OUTCOMES; THERAPY; SURGERY; MEDICINE; MEDICARE; DISEASE; RISK AB Background-In patients with severe aortic stenosis who cannot have surgery, transcatheter aortic valve replacement (TAVR) has been shown to improve survival and quality of life compared with standard therapy, but the costs and cost-effectiveness of this strategy are not yet known. Methods and Results-The PARTNER trial randomized patients with symptomatic, severe aortic stenosis who were not candidates for surgery to TAVR (n = 179) or standard therapy (n = 179). Empirical data regarding survival, quality of life, medical resource use, and hospital costs were collected during the trial and used to project life expectancy, quality-adjusted life expectancy, and lifetime medical care costs to estimate the incremental cost-effectiveness of TAVR from a US perspective. For patients treated with TAVR, mean costs for the initial procedure and hospitalization were $42 806 and $78 542, respectively. Follow-up costs through 12 months were lower with TAVR ($29 289 versus $53 621) because of reduced hospitalization rates, but cumulative 1-year costs remained higher ($106 076 versus $53 621). We projected that over a patient's lifetime, TAVR would increase discounted life expectancy by 1.6 years (1.3 quality-adjusted life-years) at an incremental cost of $79 837. The incremental cost-effectiveness ratio for TAVR was thus estimated at $50 200 per year of life gained or $61 889 per quality-adjusted life-year gained. These results were stable across a broad range of uncertainty and sensitivity analyses. Conclusions-For patients with severe aortic stenosis who are not candidates for surgery, TAVR increases life expectancy at an incremental cost per life-year gained well within accepted values for commonly used cardiovascular technologies. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. (Circulation. 2012;125:1102-1109.) C1 [Magnuson, Elizabeth A.; Wang, Kaijun; Lei, Yang; Vilain, Katherine; Cohen, David J.] Univ Missouri Kansas City, St Lukes Mid Amer Heart & Vasc Inst, Kansas City, MO 64111 USA. [Reynolds, Matthew R.; Walczak, Joshua] Harvard Clin Res Inst, Boston, MA USA. [Reynolds, Matthew R.] Boston VA Healthcare Syst, Boston, MA USA. [Kodali, Susheel K.; Smith, Craig R.; Leon, Martin B.] Columbia Presbyterian Med Ctr, New York, NY USA. [Lasala, John M.] Washington Univ, Sch Med, St Louis, MO USA. [O'Neill, William W.] Univ Miami, Sch Med, Miami, FL USA. [Davidson, Charles J.] Northwestern Univ, Sch Med, Chicago, IL USA. RP Cohen, DJ (reprint author), Univ Missouri Kansas City, Sch Med, St Lukes Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM dcohen@saint-lukes.org FU Edwards Lifesciences, Inc.; Edwards Lifesciences; Biosense Webster; Sanofi-aventis; St. Jude Medical; Medtronic; Eli Lilly; Daiichi Sankyo; Bristol-Myers Squibb; Abbott Vascular; MedRad; Merck/Schering-Plough; Eli Lilly-Daiichi Sankyo; Schering-Plough; Cordis FX This study was funded by Edwards Lifesciences, Inc.; Dr Reynolds reports receiving research support from Edwards Lifesciences, Biosense Webster, and Sanofi-aventis and consulting income from Biosense Webster, Sanofi-aventis, St. Jude Medical, and Medtronic. Dr Magnuson reports receiving grant support from Eli Lilly, Daiichi Sankyo, Sanofi-aventis, and Bristol-Myers Squibb. Dr Kodali reports receiving consulting income from Edwards Lifesciences (clinical proctor). Dr O'Neill reports receiving consulting fees from Medtronic. Dr Davidson reports receiving research support from Edwards Lifesciences and Abbott Vascular and serving on the advisory board of Abbott Vascular. Dr Smith reports receiving research support from Edwards Lifesciences. Dr Leon reports receiving research support from Edwards Lifesciences and consulting income from Medtronic, and he holds stock options in Sadra Medical. Dr Cohen reports receiving research support from Edwards Lifesciences, Medtronic, Boston Scientific, Abbott Vascular, MedRad, Merck/Schering-Plough, and Eli Lilly-Daiichi Sankyo; consulting income from Schering-Plough, Eli Lilly, Medtronic, and Cordis; and speaking honoraria from Eli Lilly, The Medicines Company, and St. Jude Medical. The other authors report no conflicts. NR 34 TC 98 Z9 111 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 6 PY 2012 VL 125 IS 9 BP 1102 EP 1109 DI 10.1161/CIRCULATIONAHA.111.054072 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 904LK UT WOS:000301197700017 PM 22308299 ER PT J AU Hiatt, WR Thomas, A Goldfine, AB AF Hiatt, William R. Thomas, Abraham Goldfine, Allison B. TI What Cost Weight Loss? SO CIRCULATION LA English DT Article DE adverse drug event; cardiovascular events; drugs; obesity; safety ID CARDIOVASCULAR RISK-FACTORS; BARIATRIC SURGERY; OBESE-PATIENTS; SIBUTRAMINE; NUCLEUS; TRIAL C1 [Hiatt, William R.] Univ Colorado, Sch Med, Div Cardiol, Dept Med, Aurora, CO 80045 USA. [Hiatt, William R.] CPC Clin Res, Aurora, CO USA. [Thomas, Abraham] Henry Ford Hosp, Div Endocrinol Diabet Bone & Mineral Disorders, Detroit, MI 48202 USA. [Goldfine, Allison B.] Joslin Diabet Ctr, Sect Clin Res, Boston, MA 02215 USA. [Goldfine, Allison B.] Harvard Univ, Sch Med, Boston, MA USA. RP Hiatt, WR (reprint author), Univ Colorado, Sch Med, Div Cardiol, Dept Med, 13199 E Montview Blvd,Suite 200, Aurora, CO 80045 USA. EM Will.Hiatt@UCDenver.edu OI Thomas, Abraham/0000-0002-3941-1195 NR 17 TC 11 Z9 12 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 6 PY 2012 VL 125 IS 9 BP 1171 EP 1177 DI 10.1161/CIRCULATIONAHA.111.023499 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 904LK UT WOS:000301197700023 PM 22392864 ER PT J AU Xu, AJ Springer, TA AF Xu, Amy J. Springer, Timothy A. TI Calcium stabilizes the von Willebrand factor A2 domain by promoting refolding SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID THROMBOTIC THROMBOCYTOPENIC PURPURA; ADAMTS-13; PLASMA; MULTIMERS; CLEAVAGE; ADHESION; BONDS AB Von Willebrand factor (VWF) is a large, multimeric plasma glycoprotein that critically mediates hemostasis at sites of vascular injury. Very large VWF multimers have the greatest thrombogenic activity, which is attenuated by cleavage in the A2 domain by the metalloproteinase ADAMTS13. ADAMTS13 proteolysis requires mechanical force to expose the scissile bond and is regulated by a calcium-binding site within A2. In this study, we characterized the interaction between VWF A2 and calcium by examining the effect of calcium on VWF A2 stability and mechanical unfolding and refolding. Isothermal calorimetry yielded a calcium binding K-d = 3.8 +/- 1.0 mu M and reversible thermal denaturation showed that 5 mM calcium stabilized the unfolding transition from 56.7 +/- 0.1 to 69.1 +/- 0.1 degrees C. Using optical tweezers to apply tensile force to single domains, we found that calcium did not affect VWF A2 unfolding, but rather enhanced refolding kinetics fivefold, resulting in a 0.9 kcal/mol stabilization in the folding activation energy in the presence of calcium. Taken together, our data demonstrate that VWF binds calcium at physiologic calcium concentrations and that calcium stabilizes VWF A2 by accelerating refolding. C1 [Springer, Timothy A.] Harvard Univ, Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst,Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Childrens Hosp Boston, Program Cellular & Mol Med, Immune Dis Inst,Sch Med, 3 Blackfan Circle,Room 3103, Boston, MA 02115 USA. EM springer@idi.harvard.edu FU National Institutes of Health (NIH) [HL-48675]; NIH/National Institute of General Medical Sciences [T32 GM008313] FX The authors thank Dr. S. C. Blacklow for isothermal calorimetry and CD equipment and advice. This work was supported by National Institutes of Health (NIH) HL-48675 (T. A. S.) and NIH/National Institute of General Medical Sciences T32 GM008313 Molecular Biophysics Training Grant (A.J.X.). A.J.X. is an MD/PhD candidate at Harvard Medical School and this work is submitted in partial fulfillment of the requirement for the PhD. NR 26 TC 24 Z9 24 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 MAR 6 PY 2012 VL 109 IS 10 BP 3742 EP 3747 DI 10.1073/pnas.1121261109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903LJ UT WOS:000301117700034 PM 22357761 ER PT J AU Lohr, JG Stojanov, P Lawrence, MS Auclair, D Chapuy, B Sougnez, C Cruz-Gordillo, P Knoechel, B Asmann, YW Slager, SL Novak, AJ Dogan, A Ansell, SM Link, BK Zou, LH Gould, J Saksena, G Stransky, N Rangel-Escareno, C Fernandez-Lopez, JC Hidalgo-Miranda, A Melendez-Zajgla, J Hernandez-Lemus, E Celis, ASCY Imaz-Rosshandler, I Ojesina, AI Jung, J Pedamallu, CS Lander, ES Habermann, TM Cerhan, JR Shipp, MA Getz, G Golub, TR AF Lohr, Jens G. Stojanov, Petar Lawrence, Michael S. Auclair, Daniel Chapuy, Bjoern Sougnez, Carrie Cruz-Gordillo, Peter Knoechel, Birgit Asmann, Yan W. Slager, Susan L. Novak, Anne J. Dogan, Ahmet Ansell, Stephen M. Link, Brian K. Zou, Lihua Gould, Joshua Saksena, Gordon Stransky, Nicolas Rangel-Escareno, Claudia Carlos Fernandez-Lopez, Juan Hidalgo-Miranda, Alfredo Melendez-Zajgla, Jorge Hernandez-Lemus, Enrique Schwarz-Cruz y Celis, Angela Imaz-Rosshandler, Ivan Ojesina, Akinyemi I. Jung, Joonil Pedamallu, Chandra S. Lander, Eric S. Habermann, Thomas M. Cerhan, James R. Shipp, Margaret A. Getz, Gad Golub, Todd R. TI Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE next-generation sequencing; human genetics; activation-induced deaminase ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; GENOME; RITUXIMAB; THERAPY; BCL2; DISRUPTION; EXOCYTOSIS; LANDSCAPE AB To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B, MLL2, BTG1, GNA13, ACTB, P2RY8, PCLO, and TNFRSF14. Further, we show that BCL2 mutations commonly occur in patients with BCL2/IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase-mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS, BRAF, and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease. C1 [Lohr, Jens G.; Stojanov, Petar; Lawrence, Michael S.; Auclair, Daniel; Sougnez, Carrie; Cruz-Gordillo, Peter; Knoechel, Birgit; Zou, Lihua; Gould, Joshua; Saksena, Gordon; Stransky, Nicolas; Ojesina, Akinyemi I.; Jung, Joonil; Pedamallu, Chandra S.; Lander, Eric S.; Getz, Gad; Golub, Todd R.] Eli & Edythe Broad Inst, Cambridge, MA 02412 USA. [Lohr, Jens G.; Stojanov, Petar; Chapuy, Bjoern; Knoechel, Birgit; Shipp, Margaret A.; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Asmann, Yan W.; Slager, Susan L.; Novak, Anne J.; Dogan, Ahmet; Ansell, Stephen M.; Habermann, Thomas M.; Cerhan, James R.] Mayo Clin Coll Med, Rochester, MN 55902 USA. [Knoechel, Birgit] Childrens Hosp Boston, Boston, MA 02115 USA. [Link, Brian K.] Univ Iowa Coll Med, Iowa City, IA 52245 USA. [Rangel-Escareno, Claudia; Carlos Fernandez-Lopez, Juan; Hidalgo-Miranda, Alfredo; Melendez-Zajgla, Jorge; Hernandez-Lemus, Enrique; Schwarz-Cruz y Celis, Angela; Imaz-Rosshandler, Ivan] Inst Nacl Med Genom, Mexico City 14610, DF, Mexico. [Lander, Eric S.; Golub, Todd R.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lander, Eric S.] MIT, Cambridge, MA 02142 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Lander, ES (reprint author), Eli & Edythe Broad Inst, Cambridge, MA 02412 USA. EM lander@broadinstitute.org RI Fernandez, Juan Carlos/C-4976-2013; Hidalgo-Miranda, Alfredo/B-2123-2010; Rangel-Escareno, Claudia/F-4587-2012; OI Fernandez, Juan Carlos/0000-0003-3680-4193; Hidalgo-Miranda, Alfredo/0000-0003-2315-3977; Rangel-Escareno, Claudia/0000-0003-1303-0834; Ojesina, Akinyemi/0000-0003-0755-3639; Cerhan, James/0000-0002-7482-178X FU Carlos Slim Health Institute; National Cancer Institute [5P01 CA092625-07, P50 CA97274] FX We thank the members of the T.R.G. laboratory, Maria Cortez, Jadwiga Grabarek, Ami S. Bhatt, Niall J. Lennon, and all members of the Broad Institute's Biological Samples Platform; Genetic Analysis Platform; and Genome Sequencing Platform, without whom this work would not have been possible. This work was conducted as part of the Slim Initiative for Genomic Medicine (SIGMA), a joint US-Mexico project funded by the Carlos Slim Health Institute, and was also supported by National Cancer Institute Grants 5P01 CA092625-07 and P50 CA97274. NR 40 TC 371 Z9 375 U1 5 U2 36 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 MAR 6 PY 2012 VL 109 IS 10 BP 3879 EP 3884 DI 10.1073/pnas.1121343109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903LJ UT WOS:000301117700057 PM 22343534 ER PT J AU Varadarajan, N Kwon, DS Law, KM Ogunniyi, AO Anahtar, MN Richter, JM Walker, BD Love, JC AF Varadarajan, Navin Kwon, Douglas S. Law, Kenneth M. Ogunniyi, Adebola O. Anahtar, Melis N. Richter, James M. Walker, Bruce D. Love, J. Christopher TI Rapid, efficient functional characterization and recovery of HIV-specific human CD8(+) T cells using microengraving SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T-cell cloning; single-cell analysis; nanowells; microarrays; soft lithography ID CYTOKINE FLOW-CYTOMETRY; VIRAL LOAD; ANTIRETROVIRAL THERAPY; VIRUS CONTROL; RESPONSES; ANTIGEN; INFECTION; ELISPOT; LYMPHOCYTES; MECHANISMS AB The nature of certain clinical samples (tissue biopsies, fluids) or the subjects themselves (pediatric subjects, neonates) often constrain the number of cells available to evaluate the breadth of functional T-cell responses to infections or therapeutic interventions. The methods most commonly used to assess this functional diversity ex vivo and to recover specific cells to expand in vitro usually require more than 106 cells. Here we present a process to identify antigen-specific responses efficiently ex vivo from 10(4)-10(5) single cells from blood or mucosal tissues using dense arrays of subnanoliter wells. The approach combines on-chip imaging cytometry with a technique for capturing secreted proteins-called "microengraving"-to enumerate antigen-specific responses by single T cells in a manner comparable to conventional assays such as ELISpot and intracellular cytokine staining. Unlike those assays, however, the individual cells identified can be recovered readily by micromanipulation for further characterization in vitro. Applying this method to assess HIV-specific T-cell responses demonstrates that it is possible to establish clonal CD8(+) T-cell lines that represent the most abundant specificities present in circulation using 100- to 1,000-fold fewer cells than traditional approaches require and without extensive genotypic analysis a priori. This rapid (<24 h), efficient, and inexpensive process should improve the comparative study of human T-cell immunology across ages and anatomic compartments. C1 [Varadarajan, Navin; Ogunniyi, Adebola O.; Love, J. Christopher] MIT, Dept Chem Engn, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Kwon, Douglas S.; Law, Kenneth M.; Anahtar, Melis N.; Walker, Bruce D.; Love, J. Christopher] MIT, Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA 02129 USA. [Kwon, Douglas S.; Law, Kenneth M.; Anahtar, Melis N.; Walker, Bruce D.; Love, J. Christopher] Harvard Univ, Charlestown, MA 02129 USA. [Kwon, Douglas S.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Richter, James M.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Love, JC (reprint author), MIT, Dept Chem Engn, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. EM clove@mit.edu RI Ghartouchent, malek/B-9088-2012; OI Varadarajan, Navin/0000-0001-7524-8228 FU Charles A. Dana Foundation; W.M. Keck Foundation; Ragon Institute of Massachusetts General Hospital; Massachusetts Institute of Technology; Harvard University; National Institute of Allergy and Infectious Diseases/National Institutes of Health [U54-AI057156]; National Institutes of Health [K08, NIGMS 5T32GM008334]; Burroughs Wellcome Fund; United Negro College-Merck FX This research was supported by the Charles A. Dana Foundation, the W.M. Keck Foundation, and the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University. N.V. received support from National Institute of Allergy and Infectious Diseases/National Institutes of Health GrantU54-AI057156. D.S.K. is supported by a National Institutes of Health Mentored Clinical Scientist Development Award (K08) and the Burroughs Wellcome Fund. A.O.O. was supported in part by National Institutes of Health Biotechnology Training Fellowship NIGMS 5T32GM008334 and by a United Negro College Fund-Merck Graduate Science Research Dissertation Fellowship. J.C.L. is a Latham Family Career Development Professor. NR 42 TC 42 Z9 43 U1 0 U2 31 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 MAR 6 PY 2012 VL 109 IS 10 BP 3885 EP 3890 DI 10.1073/pnas.1111205109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903LJ UT WOS:000301117700058 PM 22355106 ER PT J AU Annes, JP Ryu, JH Lam, K Carolan, PJ Utz, K Hollister-Lock, J Arvanites, AC Rubin, LL Weir, G Melton, DA AF Annes, Justin P. Ryu, Jennifer Hyoje Lam, Kelvin Carolan, Peter J. Utz, Katrina Hollister-Lock, Jennifer Arvanites, Anthony C. Rubin, Lee L. Weir, Gordon Melton, Douglas A. TI Adenosine kinase inhibition selectively promotes rodent and porcine islet beta-cell replication SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemical screening; regeneration ID ADULT-MOUSE PANCREAS; COMPENSATORY GROWTH; GLUCOSE-INFUSION; HUMAN-PREGNANCY; IN-VIVO; REGENERATION; EXPRESSION; PROGENITORS; ENDOCRINE; MICE AB Diabetes is a pathological condition characterized by relative insulin deficiency, persistent hyperglycemia, and, consequently, diffuse micro-and macrovascular disease. One therapeutic strategy is to amplify insulin-secretion capacity by increasing the number of the insulin-producing beta cells without triggering a generalized proliferative response. Here, we present the development of a small-molecule screening platform for the identification of molecules that increase beta-cell replication. Using this platform, we identify a class of compounds [ adenosine kinase inhibitors (ADK-Is)] that promote replication of primary beta cells in three species (mouse, rat, and pig). Furthermore, the replication effect of ADK-Is is cell type-selective: treatment of islet cell cultures with ADK-Is increases replication of beta cells but not that of alpha cells, PP cells, or fibroblasts. Short-term in vivo treatment with an ADK-I also increases beta-cell replication but not exocrine cell or hepatocyte replication. Therefore, we propose ADK inhibition as a strategy for the treatment of diabetes. C1 [Annes, Justin P.; Ryu, Jennifer Hyoje; Lam, Kelvin; Carolan, Peter J.; Utz, Katrina; Arvanites, Anthony C.; Rubin, Lee L.; Melton, Douglas A.] Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Annes, Justin P.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Annes, Justin P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Carolan, Peter J.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. [Hollister-Lock, Jennifer; Weir, Gordon] Harvard Univ, Sch Med, Dept Med, Sect Islet Cell & Regenerat Biol,Joslin Diabet Ct, Boston, MA 02115 USA. [Melton, Douglas A.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Melton, DA (reprint author), Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM dmelton@harvard.edu FU Howard Hughes Medical Institute; National Institutes of Health [DK084206, U01DK072505]; Diabetes Research and Wellness Foundation FX We thank Yuval Dor, Qiao Zhao, Dena Cohen, Jayaraj Rajagopal, Julie Sneddon, and Susan Bonner-Weir for their thoughtful input throughout the development of this work. We are grateful for the technical support of George Kenty, Kathryn Koszka, Bridget Molloy, Josh Cohen, Vaja Tchipashvili, and Karolina Siniakowicz. This work was supported by the Howard Hughes Medical Institute (D.A.M.), National Institutes of Health Grants DK084206 (to J.P.A.) and U01DK072505 (to D.A.M.), and the Diabetes Research and Wellness Foundation (G.W.). NR 53 TC 52 Z9 54 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 6 PY 2012 VL 109 IS 10 BP 3915 EP 3920 DI 10.1073/pnas.1201149109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903LJ UT WOS:000301117700063 PM 22345561 ER PT J AU Kim, TH Escudero, S Shivdasani, RA AF Kim, Tae-Hee Escudero, Silvia Shivdasani, Ramesh A. TI Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSGENIC MICE; DIFFERENTIATION; EPITHELIUM; GENE; CANCER; MATH1; MAINTENANCE; POPULATIONS; HOMEOSTASIS; ABLATION AB Lifelong self-renewal of the adult intestinal epithelium requires the activity of stem cells located in mucosal crypts. Lgr5 and Bmi1 are two molecular markers of crypt-cell populations that replenish all lineages over time and hence function as stem cells. Intestinal stem cells require Wnt signaling, but the understanding of their cellular niche is incomplete. Lgr5-expressing crypt base columnar cells (CBCs) reside deep in the crypt, mingled among mature Paneth cells that are well positioned for short-range signaling. Partial lineage ablation previously had implied that Paneth cells are nonessential constituents of the stem-cell niche, but recently their absence was reported to interfere with Lgr5(+) CBCs, resurrecting an appealing idea. However, previous mouse models failed to remove Paneth cells completely or permanently; defining the intestinal stem-cell niche requires clarity with respect to the Paneth cell role. We find that Lgr5+ cells with stem-cell activity cluster in future crypts early in life, before Paneth cells develop. We also crossed conditional Atoh1(-/-) mice, which lack Paneth cells entirely, with Lgr5(GFP) mice to visualize Lgr5(+) CBCs and to track their stem-cell function. In the sustained absence of Paneth cells, Lgr5(+) CBCs occupied the full crypt base, proliferated briskly, and generated differentiated progeny over many months. Gene expression in fluorescence-sorted Lgr5(+) CBCs reflected intact Wnt signaling despite the loss of Paneth cells. Thus, Paneth cells are dispensable for survival, proliferation, and stem-cell activity of CBCs, and direct contact with Lgr5-nonexpressing cells is not essential for CBC function. C1 [Kim, Tae-Hee; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kim, Tae-Hee; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Escudero, Silvia] Harvard Univ, Grad Program Biol & Biomed Sci, Cambridge, MA 02138 USA. [Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU National Institutes of Health [R01DK081113, R01DK082889, RC2CA148222]; Harvard Stem Cell Institute; Dana Farber-Harvard Cancer Center [P50CA127003]; Harvard Digestive Diseases Center [P50DK34854] FX We thank Andre Ouellette for generously providing Crs4c1 Ab; Sylvie Robine for kindly sharing VillinCreER mice; Susumu Ito for assisting with electron microscopy; and Li-Lun Ho, Kodanda Nalapareddy, and Michael Verzi for technical assistance and helpful discussions. This work was supported by National Institutes of Health Grants R01DK081113, R01DK082889, and RC2CA148222 and by an award from the Harvard Stem Cell Institute and was enabled by core facilities supported by the Dana Farber-Harvard Cancer Center Specialized Program in Research Excellence in Gastrointestinal Cancers Grant P50CA127003 and Harvard Digestive Diseases Center Grant P50DK34854. NR 37 TC 69 Z9 70 U1 1 U2 15 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 MAR 6 PY 2012 VL 109 IS 10 BP 3932 EP 3937 DI 10.1073/pnas.1113890109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903LJ UT WOS:000301117700066 PM 22355124 ER PT J AU Bakken, TE Roddey, JC Djurovic, S Akshoomoff, N Amaral, DG Bloss, CS Casey, BJ Chang, L Ernst, TM Gruen, JR Jernigan, TL Kaufmann, WE Kenet, T Kennedy, DN Kuperman, JM Murray, SS Sowell, ER Rimol, LM Mattingsdal, M Melle, I Agartz, I Andreassen, OA Schork, NJ Dale, AM AF Bakken, Trygve E. Roddey, J. Cooper Djurovic, Srdjan Akshoomoff, Natacha Amaral, David G. Bloss, Cinnamon S. Casey, B. J. Chang, Linda Ernst, Thomas M. Gruen, Jeffrey R. Jernigan, Terry L. Kaufmann, Walter E. Kenet, Tal Kennedy, David N. Kuperman, Joshua M. Murray, Sarah S. Sowell, Elizabeth R. Rimol, Lars M. Mattingsdal, Morten Melle, Ingrid Agartz, Ingrid Andreassen, Ole A. Schork, Nicholas J. Dale, Anders M. CA Alzheimer's Dis Neuroimaging Pediat Imaging Neurocognition TI Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE allometry; brain morphometry; imaging genetics; V1 ID GENOME-WIDE ASSOCIATION; GERMLINE MUTATIONS; MONOZYGOTIC TWINS; BRAIN STRUCTURE; CORTEX; EMX2; PAX6; SIZE; EVOLUTION; PERFORMANCE AB Visual cortical surface area varies two-to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P-combined = 3.2 x 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 x 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception. C1 [Bakken, Trygve E.; Bloss, Cinnamon S.; Murray, Sarah S.; Schork, Nicholas J.] Scripps Res Inst, Scripps Genom Med & Scripps Translat Sci Inst, La Jolla, CA 92037 USA. [Bakken, Trygve E.] Univ Calif San Diego, Med Scientist Training Program, La Jolla, CA 92093 USA. [Roddey, J. Cooper] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Djurovic, Srdjan; Rimol, Lars M.; Mattingsdal, Morten; Melle, Ingrid; Agartz, Ingrid; Andreassen, Ole A.] Univ Oslo, Inst Clin Med, N-0450 Oslo, Norway. [Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, N-0424 Oslo, Norway. [Akshoomoff, Natacha; Jernigan, Terry L.] Univ Calif San Diego, Ctr Human Dev, La Jolla, CA 92093 USA. [Akshoomoff, Natacha; Jernigan, Terry L.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Amaral, David G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. [Casey, B. J.] Weill Cornell Med Coll, Sackler Inst Dev Psychobiol, New York, NY 10065 USA. [Chang, Linda; Ernst, Thomas M.] Univ Hawaii, Dept Med, Honolulu, HI 96813 USA. [Chang, Linda; Ernst, Thomas M.] Queens Med Ctr, Honolulu, HI 96813 USA. [Gruen, Jeffrey R.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. [Gruen, Jeffrey R.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. [Jernigan, Terry L.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. [Jernigan, Terry L.; Kuperman, Joshua M.; Dale, Anders M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Kaufmann, Walter E.] Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Baltimore, MD 21205 USA. [Kenet, Tal] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Kenet, Tal] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kennedy, David N.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01605 USA. [Sowell, Elizabeth R.] Univ So Calif, Dept Pediat, Los Angeles, CA 90027 USA. [Sowell, Elizabeth R.] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA. [Mattingsdal, Morten; Melle, Ingrid; Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, N-0424 Oslo, Norway. [Agartz, Ingrid] Diakonhjemmet Hosp, Dept Res & Dev, N-0319 Oslo, Norway. [Schork, Nicholas J.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RP Schork, NJ (reprint author), Scripps Res Inst, Scripps Genom Med & Scripps Translat Sci Inst, La Jolla, CA 92037 USA. EM nschork@scripps.edu; amdale@ucsd.edu RI Kowall, Neil/G-6364-2012; Preda, Adrian /K-8889-2013; Saykin, Andrew/A-1318-2007; Melle, Ingrid /B-4858-2011; OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438; Agartz, Ingrid/0000-0002-9839-5391; Andreassen, Ole A./0000-0002-4461-3568; Saykin, Andrew/0000-0002-1376-8532; Melle, Ingrid /0000-0002-9783-548X; Norbash, Alexander/0000-0003-2986-2563; Bakken, Trygve/0000-0003-3373-7386; Rimol, Lars M./0000-0002-1243-0396; de Leon, Mony/0000-0003-2245-4380 FU Oslo University Hospital-Ulleval; South-Eastern Norway Health Authority [2004-123]; Research Council of Norway [167153/V50, 163070/V50]; Alzheimer's Disease Neuroimaging Initiative (ADNI) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Pfizer Inc.; Wyeth Research; Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; Merck and Co. Inc.; AstraZeneca AB; Novartis Pharmaceuticals Corporation; Alzheimer's Association; Eisai Global Clinical Development; Elan Corporation plc; Forest Laboratories; Institute for the Study of Aging; US Food and Drug Administration; National Institutes of Health [R01AG031224, R01AG22381, U54NS056883, P50NS22343, P50MH081755, 5UL1RR025774, U01DA024417, R01AG030474, R01MH080134, R01HL089655, U54CA143906, R01AG035020, R01DA030976, U19AG023122-01, R01MH078151-01A1, N01MH22005, RC2DA029475]; Price Foundation; Scripps Genomic Medicine FX We thank the study participants and the members of the Thematically Organized Psychosis Study group involved in data collection, especially Drs. Jimmy Jensen, Per Nakstad, and Andres Server. We also thank Eivind Bakken, Thomas Doug Bjella, Alan Koyama, Robin G. Jennings, Chris J. Pung, and Dr. Christine Fennema-Notestine. This work was supported by the Oslo University Hospital-Ulleval, South-Eastern Norway Health Authority Grant 2004-123, Research Council of Norway Grants 167153/V50 and 163070/V50, and Eli Lilly Inc. for parts of the genotyping costs of the TOP sample. Data collection and sharing for a portion of this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institute of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, and it is also funded through generous contributions from Pfizer Inc., Wyeth Research, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck and Co. Inc., AstraZeneca AB, Novartis Pharmaceuticals Corporation, Alzheimer's Association, Eisai Global Clinical Development, Elan Corporation plc, Forest Laboratories, and the Institute for the Study of Aging, with participation from the US Food and Drug Administration. Industry partnerships are coordinated through the Foundation for the National Institutes of Health. 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 at San Diego. ADNI data are disseminated by the Laboratory of Neuroimaging at the University of California, Los Angeles. This work was also supported in part by National Institutes of Health Grants R01AG031224, R01AG22381, U54NS056883, P50NS22343, P50MH081755, 5UL1RR025774, U01DA024417, R01AG030474, R01MH080134, R01HL089655, U54CA143906, R01AG035020, R01DA030976, U19AG023122-01, R01MH078151-01A1, N01MH22005, and RC2DA029475. This work was also supported by the Price Foundation and Scripps Genomic Medicine. NR 57 TC 26 Z9 26 U1 0 U2 9 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 MAR 6 PY 2012 VL 109 IS 10 BP 3985 EP 3990 DI 10.1073/pnas.1105829109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903LJ UT WOS:000301117700075 PM 22343285 ER PT J AU Ananthakrishnan, AN Higuchi, LM Huang, ES Khalili, H Richter, JM Fuchs, CS Chan, AT AF Ananthakrishnan, Ashwin N. Higuchi, Leslie M. Huang, Edward S. Khalili, Hamed Richter, James M. Fuchs, Charles S. Chan, Andrew T. TI Aspirin, Nonsteroidal Anti-inflammatory Drug Use, and Risk for Crohn Disease and Ulcerative Colitis A Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; LONG-TERM USE; SPHINGOSINE KINASE; OLMSTED COUNTY; PREVALENCE; MICE; IBD; REPRODUCIBILITY; PERMEABILITY AB Background: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory but have been linked in some studies to Crohn disease (CD) and ulcerative colitis (UC). Objective: To assess the association between aspirin and NSAID use and incident CD and UC. Design: Prospective cohort study. Setting: Nurses' Health Study I. Patients: 76 795 U. S. women who provided biennially updated data about aspirin and NSAID use. Measurements: Incident CD and UC between 1990 and 2008 (outcome) and NSAID and aspirin use (exposure). Results: 123 incident cases of CD and 117 cases of UC occurred over 18 years and 1 295 317 person-years of follow-up. Compared with nonusers, women who used NSAIDs at least 15 days per month seemed to have increased risk for both CD (absolute difference in age-adjusted incidence, 6 cases per 100 000 person-years [95% CI, 0 to 13]; multivariate hazard ratio, 1.59 [CI, 0.99 to 2.56]) and UC (absolute difference, 7 cases per 100 000 person-years [CI, 1 to 12]; multivariate hazard ratio, 1.87 [CI, 1.16 to 2.99]). Less frequent NSAID use was not clearly associated with risk for CD or UC, and there was no clear association between aspirin use and disease. Limitations: Cohort participants were exclusively women, most of whom were white. Aspirin and NSAID use were self-reported. Conclusion: Frequent use of NSAIDs but not aspirin seemed to be associated with increased absolute incidence of CD and UC. The findings have more mechanistic than clinical implications, because the absolute incidence of CD or UC associated with NSAIDs was low and the increase in risk for CD or UC associated with NSAIDs is unlikely to alter the balance of more common and clinically significant risks and benefits associated with these agents. C1 [Chan, Andrew T.] Harvard Univ, Massachusetts Gen Hosp, Gastrointestinal Unit,Childrens Hosp Boston, Brigham & Womens Hosp,Sch Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chan, AT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Gastrointestinal Unit,Childrens Hosp Boston, Brigham & Womens Hosp,Sch Med, 55 Fruit St,GRJ 722, Boston, MA 02114 USA. EM achan@partners.org FU American Gastroenterological Association; IBD Working Group; Broad Medical Research Program; National Institutes of Health [R01 CA137178, P01 CA87969, P30 DK043351, K08 DK064256]; Broad Medical Research Foundation FX American Gastroenterological Association, IBD Working Group, Broad Medical Research Program, and National Institutes of Health.; By the American Gastroenterological Association (Dr. Ananthakrishnan), the Broad Medical Research Foundation ( Dr. Chan), the IBD Working Group ( Dr. Khalili), and the National Institutes of Health (R01 CA137178, P01 CA87969, P30 DK043351, and K08 DK064256). NR 41 TC 51 Z9 52 U1 2 U2 9 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 6 PY 2012 VL 156 IS 5 BP 350 EP U170 DI 10.7326/0003-4819-156-5-201203060-00007 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 902OC UT WOS:000301046800003 PM 22393130 ER PT J AU Liu, CF Bryson, CL Burgess, JF Sharp, N Perkins, M Maciejewski, ML AF Liu, Chuan-Fen Bryson, Chris L. Burgess, James F., Jr. Sharp, Nancy Perkins, Mark Maciejewski, Matthew L. TI Use of outpatient care in VA and Medicare among disability-eligible and age-eligible veteran patients SO BMC HEALTH SERVICES RESEARCH LA English DT Article DE Outpatient; Utilization; Primary care; Veterans; Medicare ID TRAUMATIC BRAIN-INJURY; HEALTH-CARE; RISK ADJUSTMENT; DUAL ELIGIBLES; BENEFICIARIES; AFFAIRS; SERVICES; AFGHANISTAN; POPULATION; IRAQ AB Background: More than half of veterans who use Veterans Health Administration (VA) care are also eligible for Medicare via disability or age, but no prior studies have examined variation in use of outpatient services by Medicare-eligible veterans across health system, type of care or time. Objectives: To examine differences in use of VA and Medicare outpatient services by disability-eligible or age-eligible veterans among veterans who used VA primary care services and were also eligible for Medicare. Methods: A retrospective cohort study of 4,704 disability-and 10,816 age-eligible veterans who used VA primary care services in fiscal year (FY) 2000. We tracked their outpatient utilization from FY2001 to FY2004 using VA administrative and Medicare claims data. We examined utilization differences for primary care, specialty care, and mental health outpatient visits using generalized estimating equations. Results: Among Medicare-eligible veterans who used VA primary care, disability-eligible veterans had more VA primary care visits (p < 0.001) and more VA specialty care visits (p < 0.001) than age-eligible veterans. They were more likely to have mental health visits in VA (p < 0.01) and Medicare-reimbursed visits (p < 0.01). Disability-eligible veterans also had more total (VA+Medicare) visits for primary care (p < 0.01) and specialty care (p < 0.01), controlling for patient characteristics. Conclusions: Greater use of primary care and specialty care visits by disability-eligible veterans is most likely related to greater health needs not captured by the patient characteristics we employed and eligibility for VA care at no cost. Outpatient care patterns of disability-eligible veterans may foreshadow care patterns of veterans returning from Afghanistan and Iraq wars, who are entering the system in growing numbers. This study provides an important baseline for future research assessing utilizations among returning veterans who use both VA and Medicare systems. Establishing effective care coordination protocols between VA and Medicare providers can help ensure efficient use of taxpayer resources and high quality care for disabled veterans. C1 [Liu, Chuan-Fen; Bryson, Chris L.; Sharp, Nancy; Perkins, Mark] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA 98101 USA. [Liu, Chuan-Fen; Sharp, Nancy] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Bryson, Chris L.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. [Burgess, James F., Jr.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Burgess, James F., Jr.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27706 USA. RP Liu, CF (reprint author), VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM Chuan-Fen.Liu@va.gov OI Burgess, James/0000-0002-6646-7071 FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 04- 292] FX This work was supported by the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs, project number IIR 04- 292. Drs. Liu, Bryson, Sharp, and Perkins are at the Northwest Center for Outcomes Research in Older Adults at the VA Puget Sound Health Care System, Seattle Division. Dr. Burgess is at the Center for Organization, Leadership and Management Research at the VA Boston Healthcare System. Dr. Maciejewski is at Center for Health Services Research in Primary Care at the Durham VA Medical Center and a VA Research Career Scientist. The views expressed herein are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, the University of Washington, Boston University, or Duke University. NR 56 TC 2 Z9 2 U1 4 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD MAR 5 PY 2012 VL 12 AR 51 DI 10.1186/1472-6963-12-51 PG 13 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 947DV UT WOS:000304407900001 ER PT J AU Mueller, R Dawson, ES Meiler, J Rodriguez, AL Chauder, BA Bates, BS Felts, AS Lamb, JP Menon, UN Jadhav, SB Kane, AS Jones, CK Gregory, KJ Niswender, CM Conn, PJ Olsen, CM Winder, DG Emmitte, KA Lindsley, CW AF Mueller, Ralf Dawson, Eric S. Meiler, Jens Rodriguez, Alice L. Chauder, Brian A. Bates, Brittney S. Felts, Andrew S. Lamb, Jeffrey P. Menon, Usha N. Jadhav, Sataywan B. Kane, Alexander S. Jones, Carrie K. Gregory, Karen J. Niswender, Colleen M. Conn, P. Jeffrey Olsen, Christopher M. Winder, Danny G. Emmitte, Kyle A. Lindsley, Craig W. TI Discovery of 2-(2-Benzoxazoyl amino)-4-Aryl-5-Cyanopyrimidine as Negative Allosteric Modulators (NAMs) of Metabotropic Glutamate Receptor 5 (mGlu5): From an Artificial Neural Network Virtual Screen to an In Vivo Tool Compound SO CHEMMEDCHEM LA English DT Article DE addiction; allosteric modulators; artificial neural networks; metabotropic glutamate receptors; structure-activity relationships ID LOCOMOTOR-ACTIVITY; MICE; IDENTIFICATION; ANTAGONISTS; SUBTYPE-5; LEAD; 2-METHYL-6-(PHENYLETHYNYL)PYRIDINE; POTENTIATORS; PHARMACOLOGY; DISORDERS C1 [Mueller, Ralf; Meiler, Jens; Emmitte, Kyle A.; Lindsley, Craig W.] Vanderbilt Univ, Dept Chem, Stevenson Ctr 7330, Nashville, TN 37232 USA. [Dawson, Eric S.; Rodriguez, Alice L.; Chauder, Brian A.; Bates, Brittney S.; Felts, Andrew S.; Lamb, Jeffrey P.; Menon, Usha N.; Jadhav, Sataywan B.; Kane, Alexander S.; Jones, Carrie K.; Gregory, Karen J.; Niswender, Colleen M.; Conn, P. Jeffrey; Emmitte, Kyle A.; Lindsley, Craig W.] Vanderbilt Univ, Med Ctr MRBIV 12475, Dept Pharmacol, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. [Jones, Carrie K.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst TVHS, Nashville, TN 37212 USA. [Gregory, Karen J.] Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic, Australia. [Olsen, Christopher M.; Winder, Danny G.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Med Ctr, Nashville, TN 37232 USA. RP Mueller, R (reprint author), Vanderbilt Univ, Dept Chem, Stevenson Ctr 7330, Stn B 351822, Nashville, TN 37232 USA. EM jens.meiler@vanderbilt.edu; craig.lindsley@vanderbilt.edu RI Conn, Peter/D-7848-2012; Olsen, Christopher/C-3542-2008; Winder, Danny/H-4857-2013; OI Olsen, Christopher/0000-0003-2700-0310; Gregory, Karen/0000-0002-3833-2137 FU US National Institutes of Health (NIH); US National Institute on Drug Abuse (NIDA) [R01DA023947-01]; US National Institute of Mental Health (NIMH) [R01090192-01] FX The authors warmly thank the US National Institutes of Health (NIH), and in particular the US National Institute on Drug Abuse (NIDA; R01DA023947-01) and the US National Institute of Mental Health (NIMH; R01090192-01), for support of our programs in drug discovery. The authors also thank Daryl F. Venable (Vanderbilt University, Nashville, USA) for technical assistance with the calcium flux and radioligand binding assays. NR 51 TC 15 Z9 15 U1 0 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD MAR 5 PY 2012 VL 7 IS 3 SI SI BP 406 EP 414 DI 10.1002/cmdc.201100510 PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 901DQ UT WOS:000300942300009 PM 22267125 ER PT J AU Choi, SH Tanzi, RE AF Choi, Se Hoon Tanzi, Rudolph E. TI iPSCs to the Rescue in Alzheimer's Research SO CELL STEM CELL LA English DT Editorial Material ID PLURIPOTENT STEM-CELLS; DISEASE; GENE AB A crucial limitation to our understanding of Alzheimer's disease has been the inability to test hypotheses on live, patient-specific neurons. A recent study in Nature by Israel et al. (2012) reports that iPSC-derived neurons from AD patients recapitulate multiple aspects of disease pathology. C1 [Choi, Se Hoon; Tanzi, Rudolph E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,Dept Neurol, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit,Dept Neurol, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu NR 9 TC 10 Z9 11 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAR 2 PY 2012 VL 10 IS 3 BP 235 EP 236 DI 10.1016/j.stem.2012.02.011 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 908BX UT WOS:000301466500003 PM 22385650 ER PT J AU Park, D Spencer, JA Koh, BI Kobayashi, T Fujisaki, J Clemens, TL Lin, CP Kronenberg, HM Scadden, DT AF Park, Dongsu Spencer, Joel A. Koh, Bong Ihn Kobayashi, Tatsuya Fujisaki, Joji Clemens, Thomas L. Lin, Charles P. Kronenberg, Henry M. Scadden, David T. TI Endogenous Bone Marrow MSCs Are Dynamic, Fate-Restricted Participants in Bone Maintenance and Regeneration SO CELL STEM CELL LA English DT Article ID MESENCHYMAL STEM-CELLS; HEMATOPOIETIC STEM; PROGENITOR CELLS; OSTEOBLAST; MICROENVIRONMENT; NICHE; DIFFERENTIATION; SPECIFICATION; POPULATION AB Mesenchymal stem cells (MSCs) commonly defined by in vitro functions have entered clinical application despite little definition of their function in residence. Here, we report genetic pulse-chase experiments that define osteoblastic cells as short-lived and nonreplicative, requiring replenishment from bone-marrow-derived, Mx1(+) stromal cells with "MSC" features. These cells respond to tissue stress and migrate to sites of injury, supplying new osteoblasts during fracture healing. Single cell transplantation yielded progeny that both preserve progenitor function and differentiate into osteoblasts, producing new bone. They are capable of local and systemic translocation and serial transplantation. While these cells meet current definitions of MSCs in vitro, they are osteolineage restricted in vivo in growing and adult animals. Therefore, bone-marrow-derived MSCs may be a heterogeneous population with the Mx1(+) population, representing a highly dynamic and stress responsive stem/progenitor cell population of fate-restricted potential that feeds the high cell replacement demands of the adult skeleton. C1 [Park, Dongsu; Koh, Bong Ihn; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Spencer, Joel A.; Fujisaki, Joji; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Adv Microscopy Program, Boston, MA 02114 USA. [Spencer, Joel A.; Fujisaki, Joji; Lin, Charles P.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Park, Dongsu; Spencer, Joel A.; Koh, Bong Ihn; Fujisaki, Joji; Lin, Charles P.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Clemens, Thomas L.] Johns Hopkins Med, Ctr Musculoskeletal Res, Baltimore, MD 21287 USA. [Park, Dongsu; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA. EM david_scadden@harvard.edu RI Spencer, Joel/A-4590-2013 FU Leukemia & Lymphoma Society; National Institutes of Health FX We thank C. Lo Celso, S. Mukherjee, J. Schoonmaker, S. Guo, R. Schlanger, and M. Kim for advice and technical assistance; N. Jeanson, A. Catic, J. Dietrich, and D. Sykes for reading the manuscript; the HSCl/MGH CRM Flow Core (L. Prickett, K. Folz-Donahue, and D. Dombkowski); and the Leukemia & Lymphoma Society (Fellowship Award to D.P.) and the National Institutes of Health (grants to T.L.C., C.P.L., H.M.K., and D.T.S.). NR 33 TC 194 Z9 200 U1 6 U2 46 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD MAR 2 PY 2012 VL 10 IS 3 BP 259 EP 272 DI 10.1016/j.stem.2012.02.003 PG 14 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 908BX UT WOS:000301466500008 PM 22385654 ER PT J AU Cavasin, MA Demos-Davies, K Horn, TR Walker, LA Lemon, DD Birdsey, N Weiser-Evans, MCM Harral, J Irwin, DC Anwar, A Yeager, ME Li, M Watson, PA Nemenoff, RA Buttrick, PM Stenmark, KR McKinsey, TA AF Cavasin, Maria A. Demos-Davies, Kim Horn, Todd R. Walker, Lori A. Lemon, Douglas D. Birdsey, Nicholas Weiser-Evans, Mary C. M. Harral, Julie Irwin, David C. Anwar, Adil Yeager, Michael E. Li, Min Watson, Peter A. Nemenoff, Raphael A. Buttrick, Peter M. Stenmark, Kurt R. McKinsey, Timothy A. TI Selective Class I Histone Deacetylase Inhibition Suppresses Hypoxia-Induced Cardiopulmonary Remodeling Through an Antiproliferative Mechanism SO CIRCULATION RESEARCH LA English DT Article DE histone deacetylase; pulmonary hypertension; proliferation; gene expression; signaling pathways ID PULMONARY ARTERIAL-HYPERTENSION; FORKHEAD TRANSCRIPTION FACTOR; CARDIAC-HYPERTROPHY; SURVIVAL; PROLIFERATION; INFLAMMATION; ACTIVATION; EMERGENCE; GROWTH; CELLS AB Rationale: Histone deacetylase (HDAC) inhibitors are efficacious in models of hypertension-induced left ventricular heart failure. The consequences of HDAC inhibition in the context of pulmonary hypertension with associated right ventricular cardiac remodeling are poorly understood. Objective: This study was performed to assess the utility of selective small-molecule inhibitors of class I HDACs in a preclinical model of pulmonary hypertension. Methods and Results: Rats were exposed to hypobaric hypoxia for 3 weeks in the absence or presence of a benzamide HDAC inhibitor, MGCD0103, which selectively inhibits class I HDACs 1, 2, and 3. The compound reduced pulmonary arterial pressure more dramatically than tadalafil, a standard-of-care therapy for human pulmonary hypertension that functions as a vasodilator. MGCD0103 improved pulmonary artery acceleration time and reduced systolic notching of the pulmonary artery flow envelope, which suggests a positive impact of the HDAC inhibitor on pulmonary vascular remodeling and stiffening. Similar results were obtained with an independent class I HDAC-selective inhibitor, MS-275. Reduced pulmonary arterial pressure in MGCD0103-treated animals was associated with blunted pulmonary arterial wall thickening because of suppression of smooth muscle cell proliferation. Right ventricular function was maintained in MGCD0103-treated animals. Although the class I HDAC inhibitor only modestly reduced right ventricular hypertrophy, it had multiple beneficial effects on the right ventricle, which included suppression of pathological gene expression, inhibition of proapoptotic caspase activity, and repression of proinflammatory protein expression. Conclusions: By targeting distinct pathogenic mechanisms, isoform-selective HDAC inhibitors have potential as novel therapeutics for pulmonary hypertension that will complement vasodilator standards of care. (Circ Res. 2012;110:739-748.) C1 [Cavasin, Maria A.; Demos-Davies, Kim; Horn, Todd R.; Walker, Lori A.; Lemon, Douglas D.; Irwin, David C.; Buttrick, Peter M.; McKinsey, Timothy A.] Univ Colorado Denver, Dept Med, Div Cardiol, Aurora, CO 80045 USA. [Birdsey, Nicholas; Watson, Peter A.] Univ Colorado Denver, Div Endocrinol Metab & Diabet, Aurora, CO 80045 USA. [Weiser-Evans, Mary C. M.; Nemenoff, Raphael A.] Univ Colorado Denver, Div Renal Dis & Hypertens, Aurora, CO 80045 USA. [Harral, Julie; Anwar, Adil; Yeager, Michael E.; Li, Min; Stenmark, Kurt R.] Univ Colorado Denver, Dept Pediat, Div Pulm & Crit Care Med, Aurora, CO 80045 USA. [Watson, Peter A.] Denver VA Med Ctr, Denver, CO USA. RP McKinsey, TA (reprint author), Univ Colorado Denver, Dept Med, Div Cardiol, 12700 E 19th Ave, Aurora, CO 80045 USA. EM timothy.mckinsey@ucdenver.edu RI Walker, Lori/J-7098-2013 OI Walker, Lori/0000-0003-2556-8076 FU Department of Veterans Affairs FX P.A.W. was supported by a Department of Veterans Affairs Merit Award. NR 33 TC 67 Z9 68 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 2 PY 2012 VL 110 IS 5 BP 739 EP U250 DI 10.1161/CIRCRESAHA.111.258426 PG 22 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 902NP UT WOS:000301045500014 PM 22282194 ER PT J AU Mandal, PK Rossi, DJ AF Mandal, Pankaj K. Rossi, Derrick J. TI DNA-Damage-Induced Differentiation in Hematopoietic Stem Cells SO CELL LA English DT Editorial Material AB Aging of hematopoietic stem cells (HSCs) is accompanied by diminished functional potential. Wang et al. now provide evidence for an HSC-specific differentiation checkpoint mediated by the transcription factor BATF, which limits self-renewal of HSCs in response to the accumulation of DNA damage. C1 [Mandal, Pankaj K.; Rossi, Derrick J.] Harvard Univ, Program Cellular & Mol Med, Childrens Hosp Boston, Dept Stem Cell & Regenerat Biol,Immune Dis Inst, Boston, MA 02116 USA. RP Rossi, DJ (reprint author), Harvard Univ, Program Cellular & Mol Med, Childrens Hosp Boston, Dept Stem Cell & Regenerat Biol,Immune Dis Inst, Boston, MA 02116 USA. EM rossi@idi.harvard.edu RI mandal, pankaj/B-4885-2016 NR 10 TC 8 Z9 8 U1 3 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 2 PY 2012 VL 148 IS 5 BP 847 EP 848 DI 10.1016/j.cell.2012.02.011 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 901RR UT WOS:000300985000006 PM 22385954 ER PT J AU Ding, ZH Wu, CJ Jaskelioff, M Ivanova, E Kost-Alimova, M Protopopov, A Chu, GC Wang, GC Lu, X Labrot, ES Hu, J Wang, W Xiao, YH Zhang, HL Zhang, JH Zhang, JF Gan, BY Perry, SR Jiang, S Li, LR Horner, JW Wang, YA Chin, LD DePinho, RA AF Ding, Zhihu Wu, Chang-Jiun Jaskelioff, Mariela Ivanova, Elena Kost-Alimova, Maria Protopopov, Alexei Chu, Gerald C. Wang, Guocan Lu, Xin Labrot, Emma S. Hu, Jian Wang, Wei Xiao, Yonghong Zhang, Hailei Zhang, Jianhua Zhang, Jingfang Gan, Boyi Perry, Samuel R. Jiang, Shan Li, Liren Horner, James W. Wang, Y. Alan Chin, Lynda DePinho, Ronald A. TI Telomerase Reactivation following Telomere Dysfunction Yields Murine Prostate Tumors with Bone Metastases SO CELL LA English DT Article ID GENE-EXPRESSION ANALYSIS; INTRAEPITHELIAL NEOPLASIA; CANCER PROGRESSION; GENOME INSTABILITY; BREAST-CANCER; CARCINOMA; TUMORIGENESIS; MICE; PROTEIN; DAMAGE AB To determine the role of telomere dysfunction and telomerase reactivation in generating pro-oncogenic genomic events and in carcinoma progression, an inducible telomerase reverse transcriptase (mTert) allele was crossed onto a prostate cancer-prone mouse model null for Pten and p53 tumor suppressors. Constitutive telomerase deficiency and associated telomere dysfunction constrained cancer progression. In contrast, telomerase reactivation in the setting of telomere dysfunction alleviated intratumoral DNA-damage signaling and generated aggressive cancers with rearranged genomes and new tumor biological properties (bone metastases). Comparative oncogenomic analysis revealed numerous recurrent amplifications and deletions of relevance to human prostate cancer. Murine tumors show enrichment of the TGF-beta/SMAD4 network, and genetic validation studies confirmed the cooperative roles of Pten, p53, and Smad4 deficiencies in prostate cancer progression, including skeletal metastases. Thus, telomerase reactivation in tumor cells experiencing telomere dysfunction enables full malignant progression and provides a mechanism for acquisition of cancer-relevant genomic events endowing new tumor biological capabilities. C1 [Wu, Chang-Jiun; Kost-Alimova, Maria; Protopopov, Alexei; Zhang, Jianhua; Horner, James W.; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Ding, Zhihu; Wang, Guocan; Lu, Xin; Hu, Jian; Wang, Wei; Jiang, Shan; Wang, Y. Alan; DePinho, Ronald A.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Kost-Alimova, Maria; Protopopov, Alexei; Zhang, Jianhua; Horner, James W.; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA. [Ding, Zhihu; Wu, Chang-Jiun; Jaskelioff, Mariela; Ivanova, Elena; Kost-Alimova, Maria; Protopopov, Alexei; Chu, Gerald C.; Wang, Guocan; Lu, Xin; Labrot, Emma S.; Hu, Jian; Wang, Wei; Xiao, Yonghong; Zhang, Hailei; Zhang, Jianhua; Zhang, Jingfang; Gan, Boyi; Perry, Samuel R.; Jiang, Shan; Li, Liren; Horner, James W.; Wang, Y. Alan; Chin, Lynda; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Ding, Zhihu; Jaskelioff, Mariela; Wang, Guocan; Lu, Xin; Hu, Jian; Wang, Wei; Gan, Boyi; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Ding, Zhihu; Jaskelioff, Mariela; Wang, Guocan; Lu, Xin; Hu, Jian; Wang, Wei; Gan, Boyi; DePinho, Ronald A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Chu, Gerald C.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Chin, LD (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. EM lchin@mdanderson.org; rdepinho@mdanderson.org RI perumal, murugiah/D-1565-2012 FU Damon Runyon Cancer Research Foundation; Multiple Myeloma Research Foundation; Prostate Cancer Foundation; DOD [W81XWH-07-PCRP-IDA]; Robert A. and Renee E. Belfer Foundation; [NCI R01CA084628]; [U01CA141508] FX We thank S. Zhou and J.P. Morin for excellent mouse husbandry and care, J. Paik, M. Kim, and H. Ying for helpful discussion. We thank W. Hahn for shRNA constructs. Z.D. was supported by the Damon Runyon Cancer Research Foundation. Y.A.W. was supported by the Multiple Myeloma Research Foundation. This work is supported by NCI R01CA084628 (R.A.D.), U01CA141508 (L.C. and R.A.D.), the Prostate Cancer Foundation (R.A.D. and Z.D.), and DOD W81XWH-07-PCRP-IDA (R.A.D. and Z.D.). R.A.D. was an American Cancer Society Research Professor and supported by the Robert A. and Renee E. Belfer Foundation. The gene signature and technology developed in this paper have been licensed by Metamark GENETICS (http://www.metamarkgenetics.com/). L.C. and R.A.D. are the founders of Metamark GENETICS. Z.D. and C.J.W. are consultants for Metamark GENETICS. NR 57 TC 93 Z9 97 U1 1 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 2 PY 2012 VL 148 IS 5 BP 896 EP 907 DI 10.1016/j.cell.2012.01.039 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 901RR UT WOS:000300985000011 PM 22341455 ER PT J AU Zhang, Y McCord, RP Ho, YJ Lajoie, BR Hildebrand, DG Simon, AC Becker, MS Alt, FW Dekker, J AF Zhang, Yu McCord, Rachel Patton Ho, Yu-Jui Lajoie, Bryan R. Hildebrand, Dominic G. Simon, Aline C. Becker, Michael S. Alt, Frederick W. Dekker, Job TI Spatial Organization of the Mouse Genome and Its Role in Recurrent Chromosomal Translocations SO CELL LA English DT Article ID DOUBLE-STRAND BREAKS; V(D)J RECOMBINATION; SEQUENCING REVEALS; B-CELLS; C-MYC; MECHANISMS; CANCER; REARRANGEMENTS; LYMPHOCYTES; STABILITY AB The extent to which the three-dimensional organization of the genome contributes to chromosomal translocations is an important question in cancer genomics. We generated a high-resolution Hi-C spatial organization map of the G1-arrested mouse pro-B cell genome and used high-throughput genome-wide translocation sequencing to map translocations from target DNA double-strand breaks (DSBs) within it. RAG endonuclease-cleaved antigen-receptor loci are dominant translocation partners for target DSBs regardless of genomic position, reflecting high-frequency DSBs at these loci and their colocalization in a fraction of cells. To directly assess spatial proximity contributions, we normalized genomic DSBs via ionizing radiation. Under these conditions, translocations were highly enriched in cis along single chromosomes containing target DSBs and within other chromosomes and subchromosomal domains in a manner directly related to pre-existing spatial proximity. By combining two high-throughput genomic methods in a genetically tractable system, we provide a new lens for viewing cancer genomes. C1 [Zhang, Yu; Ho, Yu-Jui; Hildebrand, Dominic G.; Simon, Aline C.; Becker, Michael S.; Alt, Frederick W.] Childrens Hosp, Program Cellular & Mol Med, Immune Dis Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. [Zhang, Yu; Ho, Yu-Jui; Hildebrand, Dominic G.; Simon, Aline C.; Becker, Michael S.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Zhang, Yu; Ho, Yu-Jui; Hildebrand, Dominic G.; Simon, Aline C.; Becker, Michael S.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [McCord, Rachel Patton; Lajoie, Bryan R.; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Programs Syst Biol, Worcester, MA 01605 USA. [McCord, Rachel Patton; Lajoie, Bryan R.; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Programs Gene Funct & Express, Worcester, MA 01605 USA. RP Alt, FW (reprint author), Childrens Hosp, Program Cellular & Mol Med, Immune Dis Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu; job.dekker@umassmed.edu FU NIH [3P01CA092625-09S1, R01 HG003143]; Leukemia and Lymphoma Society of America (LLS) SCOR; W.M. Keck Foundation; German National Merit Foundation FX This work was supported by NIH grant ARRA Supplement 3P01CA092625-09S1 and a Leukemia and Lymphoma Society of America (LLS) SCOR grant to F. W. A. and by NIH grant R01 HG003143 and a W.M. Keck Foundation Distinguished Young Scholar Award to J.D. Y.Z. was supported by CRI postdoctoral fellowship. D. G. H., A. C. S., and M. G. B. were supported by the German National Merit Foundation. F. W. A. is an Investigator of the Howard Hughes Medical Institute. NR 49 TC 234 Z9 243 U1 4 U2 40 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 2 PY 2012 VL 148 IS 5 BP 908 EP 921 DI 10.1016/j.cell.2012.02.002 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 901RR UT WOS:000300985000012 PM 22341456 ER PT J AU Chipuk, JE McStay, GP Bharti, A Kuwana, T Clarke, CJ Siskind, LJ Obeid, LM Green, DR AF Chipuk, Jerry E. McStay, Gavin P. Bharti, Archana Kuwana, Tomomi Clarke, Christopher J. Siskind, Leah J. Obeid, Lina M. Green, Douglas R. TI Sphingolipid Metabolism Cooperates with BAK and BAX to Promote the Mitochondrial Pathway of Apoptosis SO CELL LA English DT Article ID RADIATION-INDUCED APOPTOSIS; PROGRAMMED CELL-DEATH; ENDOPLASMIC-RETICULUM; NEUTRAL SPHINGOMYELINASE; OUTER-MEMBRANE; BCL-2 FAMILY; CYTOCHROME-C; BH3 DOMAINS; HELA-CELLS; CERAMIDE AB Mitochondria are functionally and physically associated with heterotypic membranes, yet little is known about how these interactions impact mitochondrial outer-membrane permeabilization (MOMP) and apoptosis. We observed that dissociation of heterotypic membranes from mitochondria inhibited BAK/BAX-dependent cytochrome c (cyto c) release. Biochemical purification of neutral sphingomyelinases that correlated with MOMP sensitization suggested that sphingolipid metabolism coordinates BAK/BAX activation. Using purified lipids and enzymes, sensitivity to MOMP was achieved by in vitro reconstitution of the sphingolipid metabolic pathway. Sphingolipid metabolism inhibitors blocked MOMP from heavy membrane preparations but failed to influence MOMP in the presence of sphingolipid-reconstituted, purified mitochondria. Furthermore, the sphingolipid products, sphingosine-1-PO4 and hexadecenal, cooperated specifically with BAK and BAX, respectively. Sphingolipid metabolism was also required for cellular responses to apoptosis. Our studies suggest that BAK/BAX activation and apoptosis are coordinated through BH3-only proteins and a specific lipid milieu that is maintained by heterotypic membrane-mitochondrial interactions. C1 [Chipuk, Jerry E.; Bharti, Archana] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [McStay, Gavin P.; Green, Douglas R.] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA. [Kuwana, Tomomi] Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA 52252 USA. [Clarke, Christopher J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Siskind, Leah J.; Obeid, Lina M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. [Siskind, Leah J.; Obeid, Lina M.] Med Univ S Carolina, Dept Med, Div Gen Med & Geriatr, Charleston, SC 29425 USA. RP Chipuk, JE (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM jerry.chipuk@mssm.edu; douglas.green@stjude.org OI Chipuk, Jerry Edward/0000-0002-1337-842X; obeid, lina/0000-0002-0734-0847 FU NIH [CA157740, P20AA017067, AI52735, CA69381, AG024478]; NCI Cancer Center Core [P30CA21765]; VA Merit; VA [CDA-2]; VA REAP; ACS [IRG-97-219-11]; Cancer Center [P30 CA138313]; COBRE in Lipidomics and Pathobiology [NIH/NCRRP20 RR17677]; American Lebanese Syrian Associated Charities; March of Dimes Foundation [5-FY11-74] FX We would like to thank Dr. Ronald Gordon (MSSM) for TEM analysis; Dr. Richard Kolesnick (Memorial Sloan-Kettering) for the asm-/- liver; Dr. Joseph Opferman (SJCRH) for the MxCre bak-/- bax-/f animals; all members of the Obeid and Hannun laboratories (MUSC) for excellent discussion and training in sphingolipid biology, especially Drs. K. Alexa Orr Gandy, Stefka Spassieva, and Xingjun Wu; The Hartwell Center for Bioinformatics and Biotechnology; and members of the Kuwana Laboratory for technical assistance. This work was supported by: NIH CA157740 (to J.E.C.), pilot project from NIH P20AA017067 (to J.E.C.), NIH AI52735 (to D. R. G.), CA69381 (to D. R. G.), NIH AG024478 (to T. K.), an NCI Cancer Center Core Grant P30CA21765 (SJCRH), VA Merit (to L.M.O.), VA CDA-2 Award (to L.J.S), pilot project from the VA REAP (to L.J.S., and L.M.O.), the ACS IRG # IRG-97-219-11 (subaward to L.J.S.), Lipidomics Shared Resource of the Hollings Cancer Center supported by a Cancer Center Support Grant (P30 CA138313), pilot project (to L.J.S) from the NIH/NCRRP20 RR17677 COBRE in Lipidomics and Pathobiology, and the American Lebanese Syrian Associated Charities. This work was also supported in part by a Research Grant 5-FY11-74 from the March of Dimes Foundation (to J.E.C.). NR 62 TC 140 Z9 146 U1 0 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 2 PY 2012 VL 148 IS 5 BP 988 EP 1000 DI 10.1016/j.cell.2012.01.038 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 901RR UT WOS:000300985000018 PM 22385963 ER PT J AU Gnant, M Hortobagyi, GN Rugo, H Burris, HA Noguchi, S Pritchard, KI Baselga, J Sahmoud, T Bauly, H Piccart, M AF Gnant, M. Hortobagyi, G. N. Rugo, H. Burris, H. A. Noguchi, S. Pritchard, K. I. Baselga, J. Sahmoud, T. Bauly, H. Piccart, M. TI Everolimus Added to Exemestane Reduced Bone Markers and Disease Progression in Bone in Postmenopausal Women with Advanced Breast Cancer: Updated Results From the BOLERO-2 Trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 8th European Breast Cancer Conference (EBCC) CY MAR 21-24, 2012 CL Vienna, AUSTRIA SP European Canc Org (ECCO) C1 [Gnant, M.] Univ Vienna, Dept Surg, Vienna, Austria. [Hortobagyi, G. N.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Rugo, H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Burris, H. A.] Sarah Cannon Res Inst, Drug Dev Program, Nashville, TN USA. [Noguchi, S.] Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan. [Pritchard, K. I.] Univ Toronto, Toronto, ON, Canada. [Pritchard, K. I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Baselga, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sahmoud, T.] Novartis Pharmaceut, Florham Pk, NJ USA. [Bauly, H.] Novartis Pharma AG, Basel, Switzerland. [Piccart, M.] Inst Jules Bordet, B-1000 Brussels, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2012 VL 48 SU 3 MA 3LBA BP S2 EP S2 PG 1 WC Oncology SC Oncology GA 063VC UT WOS:000313029100004 ER PT J AU Greenstein, J AF Greenstein, Julia TI Juvenile Diabetes Research Foundation: Seeding Novel Insights in Diabetes Research SO STEM CELLS TRANSLATIONAL MEDICINE LA English DT Editorial Material C1 [Greenstein, Julia] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Greenstein, Julia] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 2157-6564 J9 STEM CELL TRANSL MED JI Stem Cells Transl. Med. PD MAR PY 2012 VL 1 IS 3 BP 175 EP 176 DI 10.5966/sctm.2012-0007 PG 2 WC Cell & Tissue Engineering SC Cell Biology GA 057NY UT WOS:000312571500006 PM 23197776 ER PT J AU Carroll, DL AF Carroll, D. L. TI Nurses perceptions of family presence in the intensive care unit during resuscitation and invasive procedures SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING LA English DT Meeting Abstract C1 [Carroll, D. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1474-5151 J9 EUR J CARDIOVASC NUR JI Eur. J. Cardiovasc. Nurs. PD MAR PY 2012 VL 11 SU 1 BP S70 EP S71 PG 2 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 046YT UT WOS:000311802500138 ER PT J AU Matura, LA Mc Donough, A Carroll, DL AF Matura, L. A. Mc Donough, A. Carroll, D. L. TI Determinants of health-related quality of life in pulmonary arterial hypertension SO EUROPEAN JOURNAL OF CARDIOVASCULAR NURSING LA English DT Meeting Abstract C1 [Matura, L. A.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Mc Donough, A.] Univ Massachusetts, Lowell, MA USA. [Carroll, D. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1474-5151 J9 EUR J CARDIOVASC NUR JI Eur. J. Cardiovasc. Nurs. PD MAR PY 2012 VL 11 SU 1 BP S82 EP S83 PG 2 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 046YT UT WOS:000311802500163 ER PT J AU Wasfy, MM Brady, TJ Abbara, S Nasir, K Hoffmann, U Cury, RC Di Carli, MF Blankstein, R AF Wasfy, Meagan M. Brady, Thomas J. Abbara, Suhny Nasir, Khurram Hoffmann, Udo Cury, Ricardo C. Di Carli, Marcelo F. Blankstein, Ron TI Comparison of cardiac computed tomography examination appropriateness under the 2010 revised versus the 2006 original Appropriate Use Criteria SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Appropriateness; Cardiac CT; CT coronary angiography; Coronary artery disease; Imaging ID CARDIOVASCULAR-MAGNETIC-RESONANCE; NORTH-AMERICAN-SOCIETY; NUCLEAR-CARDIOLOGY; INTERVENTIONS; ANGIOGRAPHY; RADIOLOGY; COLLEGE; DISEASE AB BACKGROUND: The 2006 Cardiac CT Appropriate Use Criteria (AUC) were recently revised in 2010. In addition to rating an expanded number of indications, the new criteria adjusted the appropriateness of existing indications to reflect changes in clinical practice and new evidence since 2006. OBJECTIVE: We sought to determine how the appropriateness of cardiac CT examinations performed at a tertiary-care hospital changed under the revised criteria compared with the original AUC. METHODS: Data were collected from the medical records and personal interview of 267 consecutive patients referred for cardiac CT in 2008. With the use of the 2010 and 2006 AUCs, two physicians designated each examination's indication as appropriate, inappropriate, uncertain, or "not classified" if examination indication could not be assigned. RESULTS: With the use the new 2010 AUC, a highly significant change was observed in the classification of examination appropriateness (P < 0.001), with 40% of examinations changing appropriateness level compared with the 2006 AUC. Under the 2010 AUC, there were an increased proportion of both appropriate examinations (59% vs. 45%; P < 0.001) and inappropriate examinations (15% vs. 10%: P < 0.001), and approximately the same proportion with uncertain appropriateness (13% vs. 16%; P = 0.33). Consequently, the proportion of examinations that were not classified was significantly reduced under the 2010 AUC (29% vs. 13%; P < 0.001). CONCLUSION: The revision of the AUC for cardiac CT had a significant effect on examination appropriateness. In comparison to the 2006 AUC, the 2010 AUC provided improved clarification of examination appropriateness. This shift was because of the inclusion of many previously unaddressed indications and the designation of more examinations as either appropriate or inappropriate. (C) 2012 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Wasfy, Meagan M.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Brady, Thomas J.; Abbara, Suhny; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Brady, Thomas J.; Abbara, Suhny; Hoffmann, Udo] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Nasir, Khurram] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Cury, Ricardo C.] Baptist Hosp Miami, Baptist Cardiac & Vasc Inst, Miami, FL USA. [Di Carli, Marcelo F.; Blankstein, Ron] Brigham & Womens Hosp, Dept Med & Radiol, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. RP Wasfy, MM (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, 75 Francis St,PB 147, Boston, MA 02115 USA. EM mkmurphy@gmail.com FU National Institutes of Health [1T32 HL076136-02] FX Drs. Blankstein and Nasir received financial support from the National Institutes of Health (grant 1T32 HL076136-02). NR 14 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD MAR-APR PY 2012 VL 6 IS 2 BP 99 EP 107 DI 10.1016/j.jcct.2011.12.005 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 035HL UT WOS:000310933900005 PM 22440425 ER PT J AU McKenna, JT Christie, MA Jeffrey, BA McCoy, JG Lee, E Connolly, NP Ward, CP Strecker, RE AF McKenna, J. T. Christie, M. A. Jeffrey, B. A. McCoy, J. G. Lee, E. Connolly, N. P. Ward, C. P. Strecker, R. E. TI Chronic ramelteon treatment in a mouse model of Alzheimer's disease SO ARCHIVES ITALIENNES DE BIOLOGIE LA English DT Article DE Melatonin; Alzheimer's disease; Amyloid plaques; Apoptosis; Maze learning; Ramelteon ID MELATONIN; APOPTOSIS; DEFICITS; THERAPY; SYSTEM; MICE AB Prior research has reported beneficial effects of melatonin in rodent models of Alzheimer's disease (AD). This study evaluated the effect of ramelteon (Rozerem (R), a melatonin receptor agonist) on. spatial learning & memory and neuropathological markers in a transgenic murine model of AD (the B6C3-Tg(APPswe, PSEN1dE9)85Dbo/J transgenic mouse strain; hereafter 'AD mice'). Three months of daily ramelteon treatment (similar to 3 mg/kg/day), starting at 3 months of age, did not produce an. improvement in the cognitive performance of AD mice (water maze). In contrast to wildtype control mice, AD mice did not show any evidence of having learned the location of the escape platform. The cortex and hippocampus of AD mice contained significant quantities of beta-amyloid plaques and PARP-positive (poly ADP ribose polymerase) cells, indicating apoptosis. Six months of ramelteon treatment. starting at 3 months of age, did not produce any change in these neuropathological markers. The ability of long term melatonin treatment to improve cognition and attenuate neuropathology in AD mice did not generalize to this dosage of ramelteon. C1 [McKenna, J. T.; Christie, M. A.; Jeffrey, B. A.; McCoy, J. G.; Lee, E.; Connolly, N. P.; Ward, C. P.; Strecker, R. E.] VA Boston Healthcare Syst, Res Serv, Brockton, MA 02301 USA. [McKenna, J. T.; Christie, M. A.; Jeffrey, B. A.; McCoy, J. G.; Lee, E.; Connolly, N. P.; Ward, C. P.; Strecker, R. E.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA. [Jeffrey, B. A.] Hebrew Rehabil Ctr, Inst Aging Res, Musculoskeletal Dept, Roslindale, MA USA. [McCoy, J. G.] Stonehill Coll, Dept Psychol, Easton, MA USA. [Lee, E.] SK Holdings, Psychiat Lab, Taejon 305772, South Korea. [Connolly, N. P.] American Univ, Dept Psychol, Washington, DC 20016 USA. [Ward, C. P.] Univ Houston Clear Lake, Houston, TX USA. RP McKenna, JT (reprint author), VA Boston Healthcare Syst, Res Serv, Res 151-C,940 Belmont St,Bldg 44,Rm 111, Brockton, MA 02301 USA. EM james_mckenna@hms.harvard.edu OI Jeffrey, Brianne/0000-0002-3337-4434 FU Takeda Pharmaceuticals North America, Inc.; SK Holdings; U.S. Dept. of Veterans Affairs Medical Research; NIH FX We thank Jeremy Beech, Yunren Bolortuya, Gina Ciovacco, and Jessin Varghese for technical assistance and John Franco for care of the animals. This study was supported by a grant from Takeda Pharmaceuticals North America, Inc. EL was supported by a fellowship from SK Holdings. The authors have indicated no financial conflicts of interest. Salary support for some of the investigators was from the U.S. Dept. of Veterans Affairs Medical Research and NIH. NR 23 TC 9 Z9 9 U1 0 U2 1 PU UNIV PISA PI PISA PA LUNGARNO A PACINOTTI 43, 56100 PISA, ITALY SN 0003-9829 J9 ARCH ITAL BIOL JI Arch. Ital. Biol. PD MAR PY 2012 VL 150 IS 1 BP 5 EP 14 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 031UV UT WOS:000310668800002 PM 22786833 ER PT J AU Broyles, LM Tate, JA Happ, MB AF Broyles, Lauren M. Tate, Judith A. Happ, Mary Beth TI USE OF AUGMENTATIVE AND ALTERNATIVE COMMUNICATION STRATEGIES BY FAMILY MEMBERS IN THE INTENSIVE CARE UNIT SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article ID POSTTRAUMATIC-STRESS; VENTILATED PATIENTS; CRITICAL ILLNESS; DECISION-MAKING; HIGH-RISK; PATIENT; SYMPTOMS; LIFE; ICU; EXPERIENCES AB Background Little is known about communication between patients and their family members during critical illness and mechanical ventilation in the intensive care unit, including use of augmentative and alternative communication tools and strategies. Objectives To identify (1) which augmentative and alternative communication tools families use with nonspeaking intensive care patients and how they are used, and (2) what families and nurses say about communication of family members with nonspeaking intensive care patients. Methods A qualitative secondary analysis was conducted of existing data from a clinical trial testing interventions to improve communication between nurses and intensive care patients. Narrative study data (field notes, intervention logs, nurses' interviews) from 127 critically ill adults were reviewed for evidence of family involvement with augmentative and alternative communication tools. Qualitative content analysis was applied for thematic description of family members' and nurses' accounts of patient-family communication. Results Family involvement with augmentative and alternative communication tools was evident in 44% of the 93 patients who completed the parent study protocol. Spouses or significant others communicated with patients most often. Main themes describing patient-family communication included (1) families being unprepared and unaware, (2) families' perceptions of communication effectiveness, (3) nurses deferring to or guiding patient-family communication, (4) patients' communication characteristics, and (5) families' experience with and interest in augmentative and alternative communication tools. Conclusions Assessment by skilled bedside clinicians can reveal patients' communication potential and facilitate useful augmentative and alternative communication tools and strategies for patients and their families. (American Journal of Critical Care. 2012; 21(2): e21-e32) C1 [Broyles, Lauren M.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Broyles, Lauren M.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15260 USA. [Tate, Judith A.] Univ Pittsburgh, Dept Psychiat, NIMH, Pittsburgh, PA 15260 USA. [Happ, Mary Beth] Univ Pittsburgh, Dept Acute & Tertiary Care, UPMC Hlth Syst, Sch Nursing,Chair Nursing Sci, Pittsburgh, PA 15260 USA. RP Broyles, LM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 7180 Highland Dr,151C-H, Pittsburgh, PA 15206 USA. EM Lauren.Broyles@va.gov RI Tate, Judith/C-7447-2015 FU National Institute for Nursing Research [5K24- NR010244]; National Institute for Child Health and Human Development [5R01 HD043988]; US Department of Veterans Affairs [CDA 10-014] FX This study was supported by grants (M. Happ, principal investigator) from the National Institute for Nursing Research (5K24- NR010244) and the National Institute for Child Health and Human Development (5R01 HD043988). Dr Broyles is currently supported by a Career Development Award (CDA 10-014) from the US Department of Veterans Affairs. This material is the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. Dr Tate is a National Institute of Mental Health postdoctoral research fellow in the clinical research training program in geriatric psychiatry at the University of Pittsburgh Department of Psychiatry (T32 MH19986, principal investigator, Reynolds). NR 61 TC 3 Z9 3 U1 2 U2 30 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 J9 AM J CRIT CARE JI Am. J. Crit. Care PD MAR 1 PY 2012 VL 21 IS 2 BP E21 EP E32 DI 10.4037/ajcc2012752 PG 12 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 031LC UT WOS:000310640300001 PM 22381993 ER PT J AU Burghardt, AJ Pialat, JB Kazakia, GJ Boutroy, S Patsch, J Valentinitsch, A Liu, DM Szabo, E Bogado, CE Engelke, K Zanchetta, MB Mckay, H Shane, E Boyd, SK Bouxsein, ML Chapurlat, R Khosla, S Majumdar, S AF Burghardt, Andrew J. Pialat, Jean-Baptiste Kazakia, Galateia J. Boutroy, Stephanie Patsch, Janina Valentinitsch, Alexander Liu, Danmei Szabo, Eva Bogado, Cesar E. Engelke, Klaus Zanchetta, Maria B. Mckay, Heather Shane, Elizabeth Boyd, Steven K. Bouxsein, Mary L. Chapurlat, Roland Khosla, Sundeep Majumdar, Sharmila TI MULTICENTER REPRODUCIBILITY OF CORTICAL AND TRABECULAR BONE QUALITY MEASURES ASSESSED BY HR-PQCT SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT IOF-ECCEO European Congress on Osteoporosis and Osteoarthritis / 2nd IOF-ESCEO Pre-Clinical Symposium CY MAR 21-24, 2012 CL Bordeaux, FRANCE SP Int Osteoporosis Fdn (IOF), European Soc Clin & Econom Aspects Osteoporosis & Osteoarthritis (ESCEO), Rottapharm, Madaus, Wisepress, Servier Int, Amgen, GlaxoSmithKline (GSK), MSD, B-Cube AG, Beammed, Danone, Dfine Europe, D3A, Eli Lilly, Expanscience, GE Healthcare, Hologic, IDS, Medi, Medtron, Mindways, Nycomed, Optasia Med, Pfizer C1 [Burghardt, Andrew J.; Pialat, Jean-Baptiste; Kazakia, Galateia J.; Patsch, Janina; Valentinitsch, Alexander; Majumdar, Sharmila] Univ Calif San Francisco, Musculoskeletal Quantitat Imaging Res Grp, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Pialat, Jean-Baptiste; Boutroy, Stephanie; Chapurlat, Roland] INSERM, F-69008 Lyon, France. [Pialat, Jean-Baptiste; Boutroy, Stephanie; Chapurlat, Roland] Univ Lyon, Res Unit 1033, Team 1, Lyon, France. [Boutroy, Stephanie; Shane, Elizabeth] Columbia Univ, Med Ctr, Div Endocrinol, Dept Med,Coll Phys & Surg, New York, NY USA. [Patsch, Janina; Valentinitsch, Alexander] Med Univ Vienna, Dept Radiol, Vienna, Austria. [Liu, Danmei; Mckay, Heather] Univ British Columbia, Ctr Hip Hlth & Mobil, Dept Orthoped, Vancouver, BC V5Z 1M9, Canada. [Szabo, Eva; Boyd, Steven K.] Univ Calgary, Schulich Sch Engn, Calgary, AB, Canada. [Engelke, Klaus] Inc Synarc, Hamburg, Germany. [Engelke, Klaus] Univ Erlangen Nurnberg, Inst Med Phys, D-91054 Erlangen, Germany. [Bouxsein, Mary L.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bouxsein, Mary L.] Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. [Khosla, Sundeep] Mayo Clin, Coll Med, Div Endocrinol Metab & Nutr, Dept Internal Med, Rochester, MN USA. [Bogado, Cesar E.; Zanchetta, Maria B.] Inst Buenos Aires, Buenos Aires, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2012 VL 23 SU 2 BP S184 EP S185 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 012TN UT WOS:000309259600251 ER PT J AU Rozental, T Day, C Earp, B Deschamps, L Taylor, A Bouxsein, ML AF Rozental, Tamara Day, Charles Earp, B. Deschamps, Laura Taylor, Alex Bouxsein, Mary L. TI PREMENOPAUSAL WOMEN WITH DISTAL RADIUS FRACTURES HAVE DETERIORATED TRABECULAR BONE ARCHITECTURE COMPARED TO NON-FRACTURE CONTROLS SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT IOF-ECCEO European Congress on Osteoporosis and Osteoarthritis / 2nd IOF-ESCEO Pre-Clinical Symposium CY MAR 21-24, 2012 CL Bordeaux, FRANCE SP Int Osteoporosis Fdn (IOF), European Soc Clin & Econom Aspects Osteoporosis & Osteoarthritis (ESCEO), Rottapharm, Madaus, Wisepress, Servier Int, Amgen, GlaxoSmithKline (GSK), MSD, B-Cube AG, Beammed, Danone, Dfine Europe, D3A, Eli Lilly, Expanscience, GE Healthcare, Hologic, IDS, Medi, Medtron, Mindways, Nycomed, Optasia Med, Pfizer C1 [Rozental, Tamara; Day, Charles; Earp, B.; Deschamps, Laura; Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Rozental, Tamara; Day, Charles; Earp, B.; Deschamps, Laura; Bouxsein, Mary L.] Harvard Univ, Sch Med, Boston, MA USA. [Taylor, Alex] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2012 VL 23 SU 2 BP S290 EP S291 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 012TN UT WOS:000309259600463 ER PT J AU Zamarioli, A Battaglino, R Morse, L Okubo, R Maranho, D Shimano, AC AF Zamarioli, Ariane Battaglino, Ricardo Morse, Leslie Okubo, Rodrigo Maranho, Daniel Shimano, Antonio C. TI PASSIVE STANDING AND FUNCTIONAL ELECTRICAL STIMULATION PRESERVES BONE STRENGTH IN PARAPLEGIC RATS FOLLOWING ACUTE SPINAL CORD INJURY SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT IOF-ECCEO European Congress on Osteoporosis and Osteoarthritis / 2nd IOF-ESCEO Pre-Clinical Symposium CY MAR 21-24, 2012 CL Bordeaux, FRANCE SP Int Osteoporosis Fdn (IOF), European Soc Clin & Econom Aspects Osteoporosis & Osteoarthritis (ESCEO), Rottapharm, Madaus, Wisepress, Servier Int, Amgen, GlaxoSmithKline (GSK), MSD, B-Cube AG, Beammed, Danone, Dfine Europe, D3A, Eli Lilly, Expanscience, GE Healthcare, Hologic, IDS, Medi, Medtron, Mindways, Nycomed, Optasia Med, Pfizer C1 [Zamarioli, Ariane; Okubo, Rodrigo; Maranho, Daniel; Shimano, Antonio C.] Univ Sao Paulo, Dept Biomech Med & Rehabil, Sao Paulo, Brazil. [Battaglino, Ricardo] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. [Morse, Leslie] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. RI Zamarioli, Ariane/K-7001-2012; Maranho, Daniel Augusto/C-1337-2013; Shimano, Antonio/E-1455-2014 OI Zamarioli, Ariane/0000-0002-7939-0528; Maranho, Daniel Augusto/0000-0002-3893-0292; NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2012 VL 23 SU 2 BP S415 EP S416 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 012TN UT WOS:000309259600697 ER PT J AU Bleier, BS AF Bleier, Benjamin S. TI Regional expression of epithelial MDR1/P-glycoprotein in chronic rhinosinusitis with and without nasal polyposis SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the American-Rhinologic-Society CY SEP 10, 2011 CL San Francisco, CA SP Amer Rhinol Soc (ARS) DE active efflux pumps; chronic sinusitis; inflammation; nasal polyposis; P-glycoprotein; Th1; Th2 ID P-GLYCOPROTEIN; MUCOSA AB Background: P-glycoprotein (P-gp) is a 170-kDa transmembrane glycoprotein encoded by the MDR1 (ABCB1) gene and is constitutively expressed on lower airway epithelium. P-gp has been shown to function as an immunomodulator regulating efflux of T-helper 1/T-helper 2 (Th1/Th2) cytokines from its host cell; however, its association with sinonasal inflammation has not been described. The purpose of this study is to determine the pattern and degree of epithelial P-gp expression in chronic rhinosinusitis (CRS) with nasal polyposis (CRSwNP) or CRS without nasal polyposis (CRSsNP). Methods: Institutional Review Board (IRB)-approved study utilizing sinus, septal, and inferior turbinate mucosa in patients with no disease, CRS, and CRSwNP (n = 4 each). Quantitative fluorescent immunohistochemistry (Q-FIHC) was performed using an anti-P-gp antibody and a secondary fluorescein isothiocyanate (FITC)-conjugated Fc specific fragment. Protein expression was quantified by calculating the epithelial to nonspecific background intensity ratio (4 images/subsite). Scores less than 1 suggested negligible expression. Staining ratios between patient groups and subsites were compared using a 2-tailed Student t test. Results: Among the sinus mucosa, P-gp expression in CRSwNP (1.570 +/- 0.354) was significantly greater than both CRS (1.224 +/- 0.248) and control (0.762 +/- 0.128) (p < 0.001, p = 0.002; respectively). CRS scores were significantly greater than control (p = 0.002). Among the septal mucosa, there was no significant difference between CRSwNP (0.914 +/- 0.264), CRS (1.126 +/- 0.476), or control (0.966 +/- 0.327). Among the inferior turbinate mucosa, there was no significant difference between CRSwNP (1.047 +/- 0.157), CRS (1.099 +/- 0.362), or control (0.824 +/- 0.181). Conclusion: MDR1/P-gp is overexpressed in the epithelial layer of sinus mucosa in patients with both CRSwNP and CRS relative to other sinonasal subsites. Expression in healthy mucosa is negligible. Given its known immunomodulatory function this suggests that P-gp may play a role in the pathogenesis or maintenance of chronic sinonasal inflammation. (C) 2011 ARS-AAOA, LLC. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Bleier, BS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM bleierb@gmail.com FU PHS HHS [P30 05209] NR 11 TC 14 Z9 14 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2042-6976 J9 INT FORUM ALLERGY RH JI Int. Forum Allergy Rhinol. PD MAR-APR PY 2012 VL 2 IS 2 BP 122 EP 125 DI 10.1002/alr.21004 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 007ZD UT WOS:000308926000006 PM 22223515 ER PT J AU Al Gadban, MM German, J Truman, JP Soodavar, F Riemer, EC Twal, WO Smith, KJ Heller, D Hofbauer, AF Oates, JC Hammad, SM AF Al Gadban, Mohammed M. German, Jashalynn Truman, Jean-Philip Soodavar, Farzan Riemer, Ellen C. Twal, Waleed O. Smith, Kent J. Heller, Demarcus Hofbauer, Ann F. Oates, Jim C. Hammad, Samar M. TI Lack of nitric oxide synthases increases lipoprotein immune complex deposition in the aorta and elevates plasma sphingolipid levels in lupus SO CELLULAR IMMUNOLOGY LA English DT Article DE Lupus; Nitric oxide synthase; Sphingosine 1-phosphate; Sphingosine kinase; Ceramide; Oxidized LDL ID TUMOR-NECROSIS-FACTOR; HIGH-DENSITY-LIPOPROTEIN; GIANT-CELL VASCULITIS; U937 MONOCYTIC CELLS; HUMAN T-CELLS; ENDOTHELIAL DYSFUNCTION; RHEUMATOID-ARTHRITIS; ACCELERATED ATHEROSCLEROSIS; MOLECULAR-MECHANISMS; SIGNAL-TRANSDUCTION AB Systemic lupus erythematosus (SLE) patients display impaired endothelial nitric oxide synthase (eNOS) function required for normal vasodilatation. SLE patients express increased compensatory activity of inducible nitric oxide synthase (iNOS) generating excess nitric oxide that may result in inflammation. We examined the effects of genetic deletion of NOS2 and NOS3, encoding iNOS and eNOS respectively, on accelerated vascular disease in MRL/lpr lupus mouse model. NOS2 and NOS3 knockout (KO) MRL/lpr mice had higher plasma levels of triglycerides (23% and 35%, respectively), ceramide (45% and 21%, respectively), and sphingosine 1-phosphate (S1P) (21%) compared to counterpart MRL/lpr controls. Plasma levels of the anti-inflammatory cytokine interleukin 10 (IL-10) in NOS2 and NOS3 KO MRL/lpr mice were lower (53% and 80%, respectively) than counterpart controls. Nodule-like lesions in the adventitia were detected in aortas from both NOS2 and NOS3 KO MRL/lpr mice. Immunohistochemical evaluation of the lesions revealed activated endothelial cells and lipid-laden macrophages (foam cells), elevated sphingosine kinase 1 expression, and oxidized low-density lipoprotein immune complexes (oxLDL-IC). The findings suggest that advanced vascular disease in NOS2 and NOS3 KO MRL/lpr mice maybe mediated by increased plasma triglycerides, ceramide and S1P; decreased plasma IL-10; and accumulation of oxLDL-IC in the vessel wall. The results expose possible new targets to mitigate lupus-associated complications. (C) 2012 Elsevier Inc. All rights reserved. C1 [Al Gadban, Mohammed M.; Truman, Jean-Philip; Soodavar, Farzan; Twal, Waleed O.; Smith, Kent J.; Hammad, Samar M.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [German, Jashalynn; Heller, Demarcus] Med Univ S Carolina, Coll Grad Studies, Summer Undergrad Res Program, Charleston, SC 29425 USA. [Riemer, Ellen C.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Hofbauer, Ann F.; Oates, Jim C.] Med Univ S Carolina, Dept Rheumatol & Immunol, Charleston, SC 29425 USA. [Hofbauer, Ann F.; Oates, Jim C.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Hammad, SM (reprint author), Med Univ S Carolina, Dept Regenerat Med & Cell Biol, 114 Doughty St 629A,MSC 815, Charleston, SC 29425 USA. EM hammadsm@musc.edu FU NIH [HL079274, K08AR002193, AR045476]; NIH (ARRA) [R01 HL079274-04S1]; South Carolina COBRE in Lipidomics and Pathobiology (from NCRR) [P20 RR17677]; Medical Research Service [NIH/NHLBI R25 HL092611]; Cancer Center Support Grant [P30 CA138313] FX This study was funded by NIH HL079274, NIH (ARRA) R01 HL079274-04S1, and the South Carolina COBRE in Lipidomics and Pathobiology (P20 RR17677 from NCRR) to SMH; NIH K08AR002193, NIH AR045476, and funding from Medical Research Service, Ralph H. Johnson VAMC, Charleston, to JCO; NIH/NHLBI R25 HL092611 for the MUSC College of Graduate Studies (J.G. and D.H.). We thank the MUSC Lipidomics Core Facility for sphingolipid analysis, the Histology Laboratory, Department of Pathology & Laboratory Medicine for tissue processing, and the MUSC Proteogenomics Facility for the use of the Bioplex system for cytokine determination. Imaging facilities were supported, in part, by Cancer Center Support Grant P30 CA138313 to the Hollings Cancer Center, MUSC. We thank Dr. Toshi Kawamori and Dr. Gabe Virella (MUSC) for providing antibodies. NR 80 TC 6 Z9 6 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR-APR PY 2012 VL 276 IS 1-2 BP 42 EP 51 DI 10.1016/j.cellimm.2012.03.007 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 985JQ UT WOS:000307260800007 PM 22560558 ER PT J AU Peraino, JS Hermanrud, CE Springett, L Zhang, HP Li, GY Srinivasan, S Gusha, A Sachs, DH Huang, CA Wang, ZR AF Peraino, Jaclyn Stromp Hermanrud, Christina E. Springett, Lauren Zhang, Huiping Li, Guoying Srinivasan, Srimathi Gusha, Ashley Sachs, David H. Huang, Christene A. Wang, Zhirui TI Expression and characterization of recombinant soluble porcine CD3 ectodomain molecules: Mapping the epitope of an anti-porcine CD3 monoclonal antibody 898H2-6-15 SO CELLULAR IMMUNOLOGY LA English DT Article DE Porcine CD3; 898H2-6-15 monoclonal antibody; T cell; Immunotoxin ID TOXIN-BASED IMMUNOTOXIN; LARGE-ANIMAL-MODEL; MIXED CHIMERISM; TOLERANCE; AFFINITY; COMPLEX; DISPLAY AB The porcine CD3 specific monoclonal antibody 898H2-6-15 has been used in allo- and xeno-transplantation studies as a porcine CD3 marker and as an effective T cell depletion reagent when conjugated to the diphtheria toxin mutant, CRM9. A recombinant anti-porcine CD3 immuntoxin was recently developed using single-chain variable fragments (scFv) derived from 898H2-6-15. In this study, using published sequence data, we have expressed the porcine CD3 ectodomain molecules in E. coli through inclusion body isolation and in vitro refolding approach. The expressed and refolded porcine CD3 ectodomain molecules include CD3 epsilon, CD3 gamma, CD3 delta, CD3 epsilon gamma heterodimer, CD3 epsilon delta heterodimer, CD3 epsilon gamma, single-chain fusion protein and CD3 epsilon delta single-chain fusion protein. These refolded porcine CD3 ectodomain molecules were purified with a strong anion exchange resin Poros 50HQ. ELISA analysis demonstrated that only the porcine CD3 epsilon gamma ectodomain single-chain fusion protein can bind to the porcine CD3 specific monoclonal antibody 898H2-6-15. The availability of this porcine CD3 epsilon gamma ectodomain single-chain fusion protein will allow screening for affinity matured variants of scEv derived from 898H2-6-15 to improve the recombinant anti-porcine CD3 immunotoxin. Porcine CD3 epsilon gamma ectodomain single-chain fusion protein will also be a very useful reagent to study the soluble phase interaction between porcine CD3 epsilon gamma and porcine CD3 antibodies such as 898H2-6-15. (C) 2012 Elsevier Inc. All rights reserved. C1 [Peraino, Jaclyn Stromp; Hermanrud, Christina E.; Springett, Lauren; Zhang, Huiping; Li, Guoying; Srinivasan, Srimathi; Gusha, Ashley; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Peraino, Jaclyn Stromp; Hermanrud, Christina E.; Springett, Lauren; Zhang, Huiping; Li, Guoying; Srinivasan, Srimathi; Gusha, Ashley; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Peraino, Jaclyn Stromp; Hermanrud, Christina E.; Springett, Lauren; Zhang, Huiping; Li, Guoying; Gusha, Ashley; Sachs, David H.; Huang, Christene A.; Wang, Zhirui] DF HCC MGH Recombinant Prot Express & Purificat C, Boston, MA 02129 USA. RP Wang, ZR (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-6113,13th St, Boston, MA 02129 USA. EM zhirui.wang@tbrc.mgh.harvard.edu FU National Institutes of Health [R01AI084657-02S1, R01AI084657-02S2]; Dana Farber/Harvard Cancer Center Core development grant FX The authors would like to acknowledge Drs. Josef Kurtz and Vimukthi Pathiraja for critical review of the manuscript and J. Scott Am for generation of the monoclonal antibody 898H2-6-15. This work was supported by National Institutes of Health (R01AI084657-02S1 to CAH and R01AI084657-02S2 to CAH) and Dana Farber/Harvard Cancer Center Core development grant. NR 17 TC 7 Z9 7 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 EI 1090-2163 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR-APR PY 2012 VL 276 IS 1-2 BP 162 EP 167 DI 10.1016/j.cellimm.2012.05.004 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 985JQ UT WOS:000307260800022 PM 22672968 ER PT J AU Hung, J Solis, J Handschumacher, MD Guerrero, JL Levine, RA AF Hung, Judy Solis, Jorge Handschumacher, Mark D. Guerrero, J. Luis Levine, Robert A. TI Persistence of Mitral Regurgitation Following Ring Annuloplasty: Is the Papillary Muscle Outside or Inside the Ring? SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID 3-DIMENSIONAL ECHOCARDIOGRAPHY; DETERMINANTS; DYSFUNCTION; INSIGHTS; REPAIR; VALVE; REVASCULARIZATION; MECHANISM; SEVERITY; VOLUME AB Background and aim of the study: Ischemic mitral regurgitation (IMR) often persists, despite annular ring reduction. It has been hypothesized that persistent IMR following ring annuloplasty was related to a continued tethering of the mitral leaflets, as defined by the distance by which the papillary muscles (PMs) were displaced outside the mitral annular ring. Methods: Seven sheep (four acute, three chronic) with persistent mitral regurgitation (MR) following ring annuloplasty for IMR were studied using three-dimensional (3D) echocardiography to examine the mitral valve geometry. The three stages examined were: Stage 1, baseline; Stage 2, post myocardial infarction (via ligation of the obtuse marginal branches); and Stage 3, post undersized ring annuloplasty. The 3D echocardiography measurements included mitral annular area, tethering distance from the ischemic PM to the anterior annulus, and the outside displacement of the PM relative to ring PM displacement. Results: Persistent moderate MR remained in these seven sheep following undersized ring annuloplasty (MR vena contracta change (pre versus post ring): 7.0 versus 5.8 +/- 2.4 mm, p = NS), despite a reduction in the mitral annular area of 50 +/- 18% (10.3 +/- 6.3 versus 4.7 +/- 1.3 cm(2)). Ring annuloplasty shifted the posterior annulus towards the anterior annulus, such that the infarcted PM became displaced outside the mitral annulus. The projected displacement distance of the PM outside versus inside the annular ring was 8.4 +/- 2.4 mm outside mitral annulus post ring versus 3.6 +/- 2.5 mm within mitral annulus pre ring, p <0001). The displacement distance from the infarcted PM to the mitral annulus restricted the ability of the posterior leaflet to move anteriorly, preventing effective coaptation. By multivariate analysis, this displacement distance was an important determinant of residual MR (p <0.02). Conclusion: Persistent MR following ring annuloplasty for IMR relates to persistently abnormal leaflet tethering, with restricted posterior leaflet motion due to PM displacement outside of the mitral annulus. The Journal of Heart Valve Disease 2012;21:218-224 C1 [Hung, Judy] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org FU NIH/National Institute for Biomedical Imaging and Bioengineering (NIBIB) [R21 EB005294]; NIH/(National Heart Lung Blood Institute) NHLBI [R01 HL092101, R01 038176, K24 HL67434]; Fondation Leducq, Paris, France [07CVD04]; American Society of echocardiography; Spanish Society of Cardiology FX These studies were supported in part by NIH/National Institute for Biomedical Imaging and Bioengineering (NIBIB) R21 EB005294, NIH/(National Heart Lung Blood Institute R01 HL092101 (J.H.), NIH/(National Heart Lung Blood Institute) NHLBI R01 038176 and K24 HL67434, grant 07CVD04 of Fondation Leducq, Paris, France (R.A.L.) and Echo-Investigator Award from the American Society of echocardiography (to J.H.), and an American Society of Echocardiography Career Development Award and Spanish Society of Cardiology (post-residency grant) (to J.S.). NR 32 TC 7 Z9 8 U1 0 U2 1 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAR PY 2012 VL 21 IS 2 BP 218 EP 224 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 977OX UT WOS:000306675400013 PM 22645858 ER PT J AU Clark, JW AF Clark, Jeffrey W. TI Drug Interactions: The Importance of Looking Inside Cancer Cells SO CANCER DISCOVERY LA English DT Editorial Material ID ADVANCED PANCREATIC-CANCER; GEMCITABINE; INFUSION; TRIAL AB nab-Paclitaxel increased intratumoral gemcitabine levels by reactive oxygen species-mediated degradation of cytidine deaminase, the rate-limiting enzyme in gemcitabine inactivation. This not only has implications for how this drug combination mediates anticancer effects but also demonstrates the importance of evaluating mechanisms of drug activity within malignant cells. Cancer Discovery; 2(3); 208-10. (c) 2012 AACR. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Clark, JW (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM jclark@partners.org NR 12 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2012 VL 2 IS 3 BP 208 EP 210 DI 10.1158/2159-8290.CD-12-0040 PG 3 WC Oncology SC Oncology GA 973AG UT WOS:000306322700026 PM 22585991 ER PT J AU Garraway, LA Janne, PA AF Garraway, Levi A. Jaenne, Pasi A. TI Circumventing Cancer Drug Resistance in the Era of Personalized Medicine SO CANCER DISCOVERY LA English DT Review ID CHRONIC MYELOID-LEUKEMIA; GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE INHIBITORS; SURFACE P-GLYCOPROTEIN; BRAF V600E MUTATION; ACQUIRED-RESISTANCE; BCR-ABL; BREAST-CANCER AB All successful cancer therapies are limited by the development of drug resistance. The increase in the understanding of the molecular and biochemical bases of drug efficacy has also facilitated studies elucidating the mechanism(s) of drug resistance. Experimental approaches that can help predict the eventual clinical drug resistance, coupled with the evolution of systematic genomic and proteomic technologies, are rapidly identifying novel resistance mechanisms. In this review, we provide a historical background on drug resistance and a framework for understanding the common ways by which cancers develop resistance to targeted therapies. We further discuss advantages and disadvantages of experimental strategies that can be used to identify drug resistance mechanism(s). Significance: Increased knowledge of drug resistance mechanisms will aid in the development of effective therapies for patients with cancer. We provide a summary of current knowledge on drug resistance mechanisms and experimental strategies to identify and study additional drug resistance pathways. Cancer Discovery; 2(3); 214-26. (c) 2012 AACR. C1 [Garraway, Levi A.; Jaenne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Garraway, Levi A.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Garraway, Levi A.; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Garraway, Levi A.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,M422A, Boston, MA 02215 USA. EM pasi_janne@dfci.harvard.edu FU NIH Director's New Innovator Award; Lung Cancer SPORE [P50 CA090578, R01CA135257]; Starr Cancer Consortium; Melanoma Research Alliance FX This work was supported by the NIH Director's New Innovator Award (L.A. Garraway), Lung Cancer SPORE P50 CA090578 (P.A. Janne), R01CA135257 (P.A. Janne), the Starr Cancer Consortium (L.A. Garraway), and the Melanoma Research Alliance (L.A. Garraway). NR 92 TC 154 Z9 155 U1 9 U2 50 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2012 VL 2 IS 3 BP 214 EP 226 DI 10.1158/2159-8290.CD-12-0012 PG 13 WC Oncology SC Oncology GA 973AG UT WOS:000306322700028 PM 22585993 ER PT J AU Corcoran, RB Ebi, H Turke, AB Coffee, EM Nishino, M Cogdill, AP Brown, RD Della Pelle, P Dias-Santagata, D Hung, KE Flaherty, KT Piris, A Wargo, JA Settleman, J Mino-Kenudson, M Engelman, JA AF Corcoran, Ryan B. Ebi, Hiromichi Turke, Alexa B. Coffee, Erin M. Nishino, Michiya Cogdill, Alexandria P. Brown, Ronald D. Della Pelle, Patricia Dias-Santagata, Dora Hung, Kenneth E. Flaherty, Keith T. Piris, Adriano Wargo, Jennifer A. Settleman, Jeffrey Mino-Kenudson, Mari Engelman, Jeffrey A. TI EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF-Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib SO CANCER DISCOVERY LA English DT Article ID WILD-TYPE BRAF; ANTITUMOR-ACTIVITY; MEK INHIBITORS; MELANOMA; KINASE; CELLS; KRAS; RESISTANCE; CETUXIMAB; MUTATION AB BRAF mutations occur in 10% to 15% of colorectal cancers and confer adverse outcome in the metastatic setting. Although RAF inhibitors such as vemurafenib (PLX4032) have proven effective in the treatment of BRAF-mutant melanoma, they are surprisingly ineffective in BRAF-mutant colorectal cancers, and the reason for this disparity remains unclear. Compared with BRAF-mutant melanoma cells, BRAF-mutant colorectal cancer cells were less sensitive to vemurafenib, and phospho-extracellular signal-regulated kinase (P-ERK) suppression was not sustained in response to treatment. Although transient inhibition of P-ERK by vemurafenib was observed in colorectal cancer, rapid ERK reactivation occurred through epidermal growth factor receptor (EGFR)-mediated activation of RAS and CRAF. BRAF-mutant colorectal cancers expressed greater levels of phospho-EGFR than BRAF-mutant melanomas, suggesting that colorectal cancers are specifically poised for EGFR-mediated resistance. Combined RAF and EGFR inhibition blocked reactivation of mitogen-activated protein kinase (MAPK) signaling in BRAF-mutant colorectal cancer cells and markedly improved efficacy in vitro and in vivo. These findings support the evaluation of combined RAF and EGFR inhibition in patients with BRAF-mutant colorectal cancer. SIGNIFICANCE: BRAF valine 600 (V600) mutations occur in 10% to 15% of colorectal cancers, yet these tumors show a surprisingly low clinical response rate (similar to 5%) to selective RAF inhibitors such as vemurafenib, which have produced dramatic response rates (60%-80%) in melanomas harboring the identical BRAF V600 mutation. We found that EGFR-mediated MAPK pathway reactivation leads to resistance to vemurafenib in BRAF-mutant colorectal cancers and that combined RAF and EGFR inhibition can lead to sustained MAPK pathway suppression and improved efficacy in vitro and in tumor xenografts. Cancer Discovery; 2(3); 227-35. (c) 2012 AACR. C1 [Corcoran, Ryan B.; Ebi, Hiromichi; Turke, Alexa B.; Cogdill, Alexandria P.; Brown, Ronald D.; Flaherty, Keith T.; Wargo, Jennifer A.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Corcoran, Ryan B.; Ebi, Hiromichi; Turke, Alexa B.; Flaherty, Keith T.; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Coffee, Erin M.; Hung, Kenneth E.] Tufts Med Ctr, Div Gastroenterol, Boston, MA USA. [Nishino, Michiya; Della Pelle, Patricia; Dias-Santagata, Dora; Piris, Adriano; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cogdill, Alexandria P.; Wargo, Jennifer A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Settleman, Jeffrey] Genentech Inc, San Francisco, CA 94080 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St,7th Floor, Charlestown, MA 02129 USA. EM jengelman@partners.org OI Cogdill, Alexandria/0000-0001-8917-9462; Ebi, Hiromichi/0000-0003-3155-7576 FU NIH Gastrointestinal Cancer SPORE [P50 CA127003]; K08 grant [CA120060-01, R01CA137008-01, R01CA140594, 1U01CA141457-01]; National Cancer Institute Lung SPORE [P50CA090578]; V Foundation; American Cancer Society [RSG-06-102-01-CCE]; Ellison Foundation Scholar FX This study is supported by grants from the NIH Gastrointestinal Cancer SPORE P50 CA127003, K08 grant CA120060-01, R01CA137008-01, R01CA140594, 1U01CA141457-01, National Cancer Institute Lung SPORE P50CA090578, the V Foundation, American Cancer Society RSG-06-102-01-CCE, and the Ellison Foundation Scholar (all J. A. Engelman). NR 20 TC 281 Z9 284 U1 5 U2 36 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2012 VL 2 IS 3 BP 227 EP 235 DI 10.1158/2159-8290.CD-11-0341 PG 9 WC Oncology SC Oncology GA 973AG UT WOS:000306322700029 PM 22448344 ER PT J AU Benassi, B Flavin, R Marchionni, L Zanata, S Pan, YF Chowdhury, D Marani, M Strano, S Muti, P Blandino, G Loda, M AF Benassi, Barbara Flavin, Richard Marchionni, Luigi Zanata, Silvio Pan, Yunfeng Chowdhury, Dipanjan Marani, Marina Strano, Sabrina Muti, Paola Blandino, Giovanni Loda, Massimo TI MYC Is Activated by USP2a-Mediated Modulation of MicroRNAs in Prostate Cancer SO CANCER DISCOVERY LA English DT Article ID C-MYC; TRANSCRIPTIONAL REGULATION; INDEPENDENT GROWTH; P53; EXPRESSION; CELLS; ONCOGENE; PATHWAY; HAUSP; DEUBIQUITINATION AB Ubiquitin-specific protease 2a (USP2a) is overexpressed in almost half of human prostate cancers and c-Myc is amplified in one third of these tumor types. Transgenic MYC expression drives invasive adenocarcinomas in the murine prostate. We show that overexpression of USP2a downregulates a set of microRNAs that collectively increase MYC levels by MDM2 deubiquitination and subsequent p53 inactivation. By establishing MYC as a target of miR-34b/c, we demonstrate that this cluster functions as a tumor suppressor in prostate cancer cells. We identify a distinct mRNA signature that is enriched for MYC-regulated transcripts and transcription factor binding sites in USP2a overexpressing prostate cancer cells. We demonstrate that these genes are associated with an invasive phenotype in human prostate cancer and that the proliferative and invasive properties of USP2a overexpressing cells are MYC-dependent. These results highlight an unrecognized mechanism of MYC regulation in prostate cancer and suggest alternative therapeutic strategies in targeting MYC. SIGNIFICANCE: The deubiquitinating enzyme USP2a has previously been shown to be oncogenic, overexpressed in almost half of human prostate adenocarcinomas, and prolongs the half-life of targets such as fatty acid synthase, MDM2, and cyclin D1. Here, we highlight a new mechanism by which USP2a enhances MYC levels through the modulation of specific subsets of microRNAs in prostate cancer, suggesting alternative therapeutic strategies for targeting MYC. Cancer Discovery; 2(3); 236-47. (c) 2012 AACR. C1 [Benassi, Barbara] ENEA Casaccia, Toxicol Lab, Rome, Italy. [Flavin, Richard; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Zanata, Silvio; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med Oncol, Boston, MA 02115 USA. [Pan, Yunfeng; Chowdhury, Dipanjan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Loda, Massimo] Broad Inst Harvard & MIT, Cambridge, MA USA. [Marchionni, Luigi] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. [Zanata, Silvio] Univ Fed Parana, Dept Basic Pathol & Cell Biol, BR-80060000 Curitiba, Parana, Brazil. [Loda, Massimo] Kings Coll London, London Sch Med, Div Canc Studies, London WC2R 2LS, England. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM blandino@ifo.it; massimo_loda@dfci.harvard.edu RI Blandino, Giovanni/B-1137-2013; strano, sabrina/B-6743-2013; OI Blandino, Giovanni/0000-0002-6970-2241; strano, sabrina/0000-0002-6341-4230; Marani, Marina/0000-0003-1585-3586 FU National Cancer Institute [RO1CA131945, PO1CA89021, P50CA90381]; NIH grant [P30CA006973]; European Community (EC) Active p53 Program; Brazilian Government FX This work was supported by National Cancer Institute grants RO1CA131945, PO1CA89021, and P50CA90381 to M. Loda and a gift from Nuclea Biomarkers to the laboratory of M. Loda; NIH grant P30CA006973 to L. Marchionni; and European Community (EC) Active p53 Program to G. Blandino. Sabbatical research fellowship (CAPES #3665/10-0) and salary support are provided by Brazilian Government to S. Zanata. NR 47 TC 30 Z9 31 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD MAR PY 2012 VL 2 IS 3 BP 236 EP 247 DI 10.1158/2159-8290.CD-11-0219 PG 12 WC Oncology SC Oncology GA 973AG UT WOS:000306322700030 PM 22585994 ER PT J AU Mitchell, C AF Mitchell, Christine TI AN INTERVIEW WITH JANE D. SCHABERG SO JOURNAL OF FEMINIST STUDIES IN RELIGION LA English DT Article C1 [Mitchell, Christine] Harvard Univ, Sch Divin, Cambridge, MA 02138 USA. [Mitchell, Christine] Dana Farber Canc Inst, Sch Divin, Boston, MA 02115 USA. [Mitchell, Christine] Brigham & Womens Hosp, Sch Divin, Boston, MA 02115 USA. RP Mitchell, C (reprint author), Harvard Univ, Sch Divin, Cambridge, MA 02138 USA. EM cmitchell@mail.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU INDIANA UNIV PRESS PI BLOOMINGTON PA 601 N MORTON STREET, BLOOMINGTON, IN 47404-3797 USA SN 8755-4178 J9 J FEMINIST STUD REL JI J. Fem. Stud. Relig. PD SPR PY 2012 VL 28 IS 1 BP 63 EP 73 PG 11 WC Religion SC Religion GA 970WQ UT WOS:000306163400005 ER PT J AU Bromley, E Adams, GF Brekke, JS AF Bromley, Elizabeth Adams, Gail Fox Brekke, John S. TI A Video Ethnography Approach for Linking Naturalistic Behaviors to Research Constructs of Neurocognition in Schizophrenia SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ECOLOGICAL MOMENTARY ASSESSMENT; COMPLEX FIGURE TEST; QUALITY-OF-LIFE; COGNITIVE DEFICITS; SOCIAL COGNITION; CODING SYSTEM; TIME USE; NEUROPSYCHOLOGICAL ASSESSMENT; SELF-DETERMINATION; BIPOLAR DISORDER AB Few methods are available to explore the impact of neurocognition in schizophrenia on behaviors performed in usual contexts. The authors developed a video ethnography approach to examine the relationship between naturalistic behaviors and research constructs of neurocognition. Video ethnographers accompanied subjects through usual routines gathering continuous video data. Researchers developed codes to measure four behavioral domains observed on video. This paper describes the psychometric characteristics to be considered in the development of observational approaches. It also highlights differences between behaviors performed in usual environments and neuropsychological constructs. The authors demonstrate that everyday behaviors that have been shown to correspond to neurocognitive skills in a pilot feasibility study can be identified and rated. They further suggest that observational methods could provide novel strategies for linking research findings and clinical concerns. (The Journal of Neuropsychiatry and Clinical Neurosciences 2012; 24:125-140) C1 [Bromley, Elizabeth; Adams, Gail Fox; Brekke, John S.] Univ Calif Los Angeles, Ctr Hlth Serv & Soc, Semel Inst,Dept Psychiat & Biobehav Sci, W Los Angeles VA Healthcare Ctr,Desert Pacific Mi, Los Angeles, CA 90024 USA. RP Bromley, E (reprint author), 10920 Wilshire Blvd,Suite 300, Los Angeles, CA USA. EM ebromley@ucla.edu FU VA Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC); University of California, Los Angeles Faculty Senate Council on Research; Foundation for Psychocultural Research-UCLA Center for Culture, Brain and Development; University of Southern California Clinical and Translational Science Institute (CTSI) FX This work was supported by the VA Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC; Bromley, PI); the University of California, Los Angeles Faculty Senate Council on Research (Bromley, PI); the Foundation for Psychocultural Research-UCLA Center for Culture, Brain and Development (Adams), and the University of Southern California Clinical and Translational Science Institute (CTSI; Brekke, PI). NR 144 TC 0 Z9 0 U1 5 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2012 VL 24 IS 2 BP 125 EP 140 PG 16 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 972MN UT WOS:000306281300101 PM 22772661 ER PT J AU Meyer, HB Katsman, A Sones, AC Auerbach, DE Ames, D Rubin, RT AF Meyer, Hilary B. Katsman, Alina Sones, Alexander C. Auerbach, Daniel E. Ames, Donna Rubin, Robert T. TI Yoga as an Ancillary Treatment for Neurological and Psychiatric Disorders: A Review SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; MULTIPLE-SCLEROSIS; REFRACTORY EPILEPSY; BIPOLAR DISORDER; DEPRESSION SCALE; MENTAL-HEALTH; HATHA-YOGA; THERAPY; SCHIZOPHRENIA; MEDITATION AB Yoga is gaining acceptance as an ancillary medical treatment, but there have been few studies evaluating its therapeutic benefits in neurological and major psychiatric conditions. The authors reviewed the literature in English on the efficacy of yoga for these disorders. Only randomized, controlled trials were included, with the exception of the only study of yoga for bipolar disorder, which was observational. Trials were excluded if yoga was not the central component of the intervention. Of seven randomized, controlled trials of yoga in patients with neurological disorders, six found significant, positive effects. Of 13 randomized, controlled trials of yoga in patients with psychiatric disorders, 10 found significant, positive effects. These results, although encouraging, indicate that additional randomized, controlled studies are needed to critically define the benefits of yoga for both neurological and psychiatric disorders. (The Journal of Neuropsychiatry and Clinical Neurosciences 2012; 24:152-164) C1 [Ames, Donna; Rubin, Robert T.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Meyer, Hilary B.] W Los Angeles VA Med Ctr, Dept Psychiat, Los Angeles, CA USA. [Sones, Alexander C.] Washington Univ, St Louis, MO 63130 USA. [Auerbach, Daniel E.] Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Ames, D (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. EM donna.ames@va.gov NR 93 TC 11 Z9 11 U1 1 U2 26 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2012 VL 24 IS 2 BP 152 EP 164 PG 13 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 972MN UT WOS:000306281300103 PM 22772663 ER PT J AU Beversdorf, DQ Nordgren, RE Bonab, AA Fischman, AJ Weise, SB Dougherty, DD Felopulos, GJ Zhou, FC Bauman, ML AF Beversdorf, David Q. Nordgren, Richard E. Bonab, Ali A. Fischman, Alan J. Weise, Steven B. Dougherty, Darin D. Felopulos, Gretchen J. Zhou, Feng C. Bauman, Margaret L. TI 5-HT2 Receptor Distribution Shown by [F-18] Setoperone PET in High-Functioning Autistic Adults SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID TRANSPORTER BINDING; SEROTONIN; DISORDER; CHILDREN; ANXIETY; SPECT; DEPRESSION; LANGUAGE; SYSTEM AB The serotonergic system is implicated in disordered emotional behavior. Autism is characterized by impaired processing of emotional information. The serotonergic (5-HT) system is also critically involved in brain development, and abnormal brain synthesis of serotonin is observed in autism. Furthermore, whole blood and platelet serotonin have been reported to be elevated in autism. The authors examined the CNS serotonin system in autism in vivo. 5-HT2 receptors were visualized by PET imaging of [F-18] setoperone-binding in this pilot study of 6 high-functioning autistic adults and 10 matched-control participants. Autism subjects had less thalamic [F-18] setoperone binding than controls, when covaried for age, but no difference reached significance in other areas. A negative relationship between thalamic binding and history of language impairment was also observed. Further studies will be needed to gain a clearer picture of the role of the 5-HT system in autism. (The Journal of Neuropsychiatry and Clinical Neurosciences 2012; 24:191-197) C1 [Beversdorf, David Q.] Univ Missouri, Dept Radiol, Columbia, MO 65211 USA. [Beversdorf, David Q.] Univ Missouri, Dept Neurol, Columbia, MO 65211 USA. [Beversdorf, David Q.] Univ Missouri, Dept Psychol Sci, Columbia, MO 65211 USA. [Beversdorf, David Q.] Univ Missouri, Thompson Ctr, Columbia, MO 65211 USA. [Nordgren, Richard E.] Dartmouth Med Sch, Dept Pediat & Med Neurol, Hanover, NH USA. [Bonab, Ali A.; Fischman, Alan J.; Weise, Steven B.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. [Dougherty, Darin D.; Felopulos, Gretchen J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Bauman, Margaret L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Beversdorf, DQ (reprint author), Univ Missouri, Dept Radiol, Columbia, MO 65211 USA. EM beversdorfd@health.missouri.edu RI Beversdorf, David/M-2786-2016 OI Beversdorf, David/0000-0002-0298-0634 FU Stallone Fund, Los Angeles, CA FX This research was funded by a grant from the Stallone Fund, Los Angeles, CA. NR 36 TC 9 Z9 9 U1 4 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2012 VL 24 IS 2 BP 191 EP 197 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 972MN UT WOS:000306281300107 PM 22772667 ER PT J AU Patti, JA AF Patti, John A. TI Radiology's Role in Enhanced International Health Care SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Patti, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM jpatti@partners.org NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD MAR PY 2012 VL 9 IS 3 BP 155 EP 155 DI 10.1016/j.jacr.2012.01.017 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 961FL UT WOS:000305449500001 PM 22386156 ER PT J AU Fixen, KR Janakiraman, A Garrity, S Slade, DJ Gray, AN Karahan, N Hochschild, A Goldberg, MB AF Fixen, Kathryn R. Janakiraman, Anuradha Garrity, Sean Slade, Daniel J. Gray, Andrew N. Karahan, Nilay Hochschild, Ann Goldberg, Marcia B. TI Genetic Reporter System for Positioning of Proteins at the Bacterial Pole SO MBIO LA English DT Article ID CELL-DIVISION PROTEINS; ESCHERICHIA-COLI K-12; AMP RECEPTOR PROTEIN; ACTIN-BASED MOTILITY; SHIGELLA-FLEXNERI; INTRACELLULAR MOVEMENT; UNIPOLAR LOCALIZATION; SEPTAL LOCALIZATION; BETA-LACTAMASE; RNA-POLYMERASE AB Spatial organization within bacteria is fundamental to many cellular processes, although the basic mechanisms underlying localization of proteins to specific sites within bacteria are poorly understood. The study of protein positioning has been limited by a paucity of methods that allow rapid large-scale screening for mutants in which protein positioning is altered. We developed a genetic reporter system for protein localization to the pole within the bacterial cytoplasm that allows saturation screening for mutants in Escherichia coli in which protein localization is altered. Utilizing this system, we identify proteins required for proper positioning of the Shigella autotransporter IcsA. Autotransporters, widely distributed bacterial virulence proteins, are secreted at the bacterial pole. We show that the conserved cell division protein FtsQ is required for localization of IcsA and other autotransporters to the pole. We demonstrate further that this system can be applied to the study of proteins other than autotransporters that display polar positioning within bacterial cells. IMPORTANCE Many proteins localize to specific sites within bacterial cells, and localization to these sites is frequently critical to proper protein function. The mechanisms that underlie protein localization are incompletely understood, in part because of the paucity of methods that allow saturation screening for mutants in which protein localization is altered. We developed a genetic reporter assay that enables screening of bacterial populations for changes in localization of proteins to the bacterial pole, and we demonstrate the utility of the system in identifying factors required for proper localization of the polar Shigella autotransporter protein IcsA. Using this method, we identify the conserved cell division protein FtsQ as being required for positioning of IcsA to the bacterial pole. We demonstrate further that the requirement for FtsQ for polar positioning applies to other autotransporters and that the method can be applied to polar proteins other than autotransporters. C1 [Fixen, Kathryn R.; Garrity, Sean; Gray, Andrew N.; Hochschild, Ann; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Janakiraman, Anuradha; Slade, Daniel J.; Goldberg, Marcia B.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Cambridge, MA USA. [Karahan, Nilay] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Goldberg, MB (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. EM mgoldberg1@partners.org OI Slade, Daniel/0000-0001-5634-7220 FU National Institutes of Health [R01 AI035817]; American Heart Association fellowship [0425855T] FX This work was supported by Public Health Service grant R01 AI035817 from the National Institutes of Health (to M.B.G.) and American Heart Association fellowship 0425855T (to A.J.). NR 38 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAR-APR PY 2012 VL 3 IS 2 AR e00251-11 DI 10.1128/mBio.00251-11 PG 9 WC Microbiology SC Microbiology GA 959FA UT WOS:000305297100022 ER PT J AU Fagenholz, PJ AF Fagenholz, Peter J. TI The role of serum proteins in sepsis SO VIRULENCE LA English DT Editorial Material DE sepsis; LTA; serum protein; LPS; host-pathogen interactions ID SEPTIC SHOCK C1 [Fagenholz, Peter J.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Crit Care, Boston, MA 02114 USA. [Fagenholz, Peter J.] Harvard Univ, Sch Med, Boston, MA USA. RP Fagenholz, PJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Crit Care, Boston, MA 02114 USA. EM pfagenholz@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD MAR-APR PY 2012 VL 3 IS 2 BP 107 EP 108 DI 10.4161/viru.19830 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 963GG UT WOS:000305607700002 PM 22460633 ER PT J AU El Khoury, J AF El Khoury, Joseph TI The blood-brain barrier and pathogens Hadrian's Wall or a Dardanian gate? SO VIRULENCE LA English DT Editorial Material DE blood-brain barrier; endothelial cells; HTLV-1; HIV; Listeria monocytogenes; Cryptococcus neoformans; Plasmodium falciparum; Toxoplasma gondii; Trypanosoma crusii C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Neuroimmunol Lab, Div Infect Dis, Charlestown, MA 02129 USA. RP El Khoury, J (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Neuroimmunol Lab, Div Infect Dis, Charlestown, MA 02129 USA. EM jelkhoury@partners.org NR 16 TC 4 Z9 4 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD MAR-APR PY 2012 VL 3 IS 2 BP 157 EP 158 DI 10.4161/viru.19751 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 963GG UT WOS:000305607700008 PM 22460634 ER PT J AU Dunn, GP Nahed, BV Walcott, BP Jung, H Tierney, TS Ogilvy, CS AF Dunn, Gavin P. Nahed, Brian V. Walcott, Brian P. Jung, Henry Tierney, Travis S. Ogilvy, Christopher S. TI Dual Ipsilateral Craniotomies Through a Single Incision for the Surgical Management of Multiple Intracranial Aneurysms SO WORLD NEUROSURGERY LA English DT Article DE Dual craniotomies; Multiple intracranial aneurysms ID BILATERAL CEREBRAL ANEURYSMS; ARTERY ANEURYSMS; RISKS; SURGERY; ANXIETY AB OBJECTIVE: To examine whether multiple aneurysms located in the anterior cerebral artery (ACA), middle cerebral artery (MCA), or internal carotid artery (ICA) could be treated through single-stage, ipsilateral dual craniotomies. METHODS: Investigators reviewed records of nine patients who underwent dual ipsilateral craniotomies through one incision for surgical treatment of multiple aneurysms in the anterior circulation at a single institution from 1994-2010. In all cases, a single-stage pterional and frontal interhemispheric approach through two separate, ipsilateral craniotomies under a single, extended pterional incision was used. RESULTS: Dual craniotomies through one incision were performed on nine patients with multiple aneurysms without complications. This series included eight women and one man with an average age of 57 years. The mean number of aneurysms treated was 2.7 (range 2-5 aneurysms). Most patients underwent elective treatment. The pterional craniotomy approach was used to treat MCA and ICA aneurysms, whereas distal ACA aneurysms were treated through the frontal parasagittal craniotomy approach. All aneurysms were successfully treated via clip ablation. There were no perioperative or postoperative complications at an average follow-up of 29 months (range 1-131 months). CONCLUSIONS: Single-stage, ipsilateral dual pterional and frontal craniotomies through one incision constitute a safe approach that can be employed for the effective surgical treatment of multiple aneurysms in joint unilateral and axial locations with excellent clinical results. C1 [Dunn, Gavin P.; Nahed, Brian V.; Walcott, Brian P.; Jung, Henry; Tierney, Travis S.; Ogilvy, Christopher S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. EM cogilvy@partners.org NR 21 TC 3 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 J9 WORLD NEUROSURG JI World Neurosurg. PD MAR-APR PY 2012 VL 77 IS 3-4 BP 502 EP 506 DI 10.1016/j.wneu.2011.07.005 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 961GG UT WOS:000305451600036 PM 22120339 ER PT J AU Braunstein, I Werth, VP AF Braunstein, Inbal Werth, Victoria P. TI Update on management of connective tissue panniculitides SO DERMATOLOGIC THERAPY LA English DT Article DE dermatomyositis; lupus erythematosus panniculitis; lupus profundus; morphea; morphea profunda ID LUPUS-ERYTHEMATOSUS PANNICULITIS; OF-THE-LITERATURE; T-CELL LYMPHOMA; LOCALIZED SCLERODERMA; SYSTEMIC-SCLEROSIS; JUVENILE DERMATOMYOSITIS; CUTANEOUS MANIFESTATION; LINEAR SCLERODERMA; MORPHEA PROFUNDA; DEEP MORPHEA AB In connective tissue diseases, panniculitis can be the sole manifestation or can occur along with the underlying disease process. The best described forms of connective tissue panniculitis are lupus erythematosus panniculitis and lupus profundus, panniculitis associated with dermatomyositis, and morphea- and scleroderma-associated panniculitis. These processes cause significant morbidity, such as deep atrophic scars, cosmetic disfigurement, and psychiatric sequelae. Because the inflammation is located in the subcutaneous adipose layer, topical therapies may not penetrate enough to be effective, and systemic agents are required. Despite the large number of reported cases and therapies, recommendations for treatment are based largely on case series and expert opinion due to a lack of controlled therapeutic trials. All treatments are off-label in the United States. The lack of validated clinical outcome measures makes systematic and controlled studies difficult. Nonetheless, further investigation into the most effective therapies for these conditions is needed. C1 [Braunstein, Inbal; Werth, Victoria P.] Univ Penn, Dept Dermatol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Div Dermatol, Philadelphia, PA USA. RP Werth, VP (reprint author), Hosp Univ Penn, Dept Dermatol, PCAM Suite 1-330S,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development); National Institutes of Health (NIH) [K24-AR 02207] FX This material is based upon work supported by the Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development) and by the National Institutes of Health (NIH K24-AR 02207) to VPW. No conflict of interest to report. NR 83 TC 4 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1396-0296 EI 1529-8019 J9 DERMATOL THER JI Dermatol. Ther. PD MAR-APR PY 2012 VL 25 IS 2 SI SI BP 173 EP 182 DI 10.1111/j.1529-8019.2012.01489.x PG 10 WC Dermatology SC Dermatology GA 959AK UT WOS:000305281900006 PM 22741936 ER PT J AU Schnall, E Kalkstein, S Fitchett, G Salmoirago-Blotcher, E Ockene, J Tindle, HA Thomas, A Hunt, JR Wassertheil-Smoller, S AF Schnall, Eliezer Kalkstein, Solomon Fitchett, George Salmoirago-Blotcher, Elena Ockene, Judith Tindle, Hilary Aurora Thomas, Asha Hunt, Julie R. Wassertheil-Smoller, Sylvia TI Psychological and Social Characteristics Associated with Religiosity in Women's Health Initiative Participants SO JOURNAL OF RELIGION & HEALTH LA English DT Article DE Religion and health; Religion and psychology; Religious behavior and health; Religious attendance and health; Religious behavior and social support; Religious behavior and social strain; Religious behavior and psychological characteristics ID PHYSICAL HEALTH; SUPPORT; MORTALITY; ATTENDANCE; DETERMINANT; INTEGRATION; HOSTILITY; OPTIMISM; ANXIETY; HISTORY AB Measures of religiosity are linked to health outcomes, possibly indicating mediating effects of associated psychological and social factors. We examined cross-sectional data from 92,539 postmenopausal participants of the Women's Health Initiative Observational Study who responded to questions on religious service attendance, psychological characteristics, and social support domains. We present odds ratios from multiple logistic regressions controlling for covariates. Women attending services weekly during the past month, compared with those not attending at all in the past month, were less likely to be depressed [OR = 0.78; CI = 0.74-0.83] or characterized by cynical hostility [OR = 0.94; CI = 0.90-0.98], and more likely to be optimistic [OR = 1.22; CI = 1.17-1.26]. They were also more likely to report overall positive social support [OR = 1.28; CI = 1.24-1.33], as well as social support of four subtypes (emotional/informational support, affection support, tangible support, and positive social interaction), and were less likely to report social strain [OR = 0.91; CI = 0.88-0.94]. However, those attending more or less than weekly were not less likely to be characterized by cynical hostility, nor were they less likely to report social strain, compared to those not attending during the past month. C1 [Schnall, Eliezer] Yeshiva Univ, Yeshiva Coll, New York, NY 10033 USA. [Kalkstein, Solomon] Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. [Fitchett, George] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Salmoirago-Blotcher, Elena; Ockene, Judith] Univ Massachusetts, Sch Med, Worcester, MA USA. [Tindle, Hilary Aurora] Univ Pittsburgh, Pittsburgh, PA USA. [Thomas, Asha] Sinai Hosp, Baltimore, MD 21215 USA. [Hunt, Julie R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, New York, NY USA. RP Schnall, E (reprint author), Yeshiva Univ, Yeshiva Coll, 500 W 185th St, New York, NY 10033 USA. EM schnall@yu.edu OI Salmoirago-Blotcher, Elena/0000-0003-4636-8698 FU NCI NIH HHS [R01 CA141596]; WHI NIH HHS [N01WH42110, N01WH22110, N01WH24152, N01WH32100, N01WH32101, N01WH32102, N01WH32105, N01WH32106, N01WH32108, N01WH32109, N01WH32111, N01WH32112, N01WH32113, N01WH32115, N01WH32118, N01WH32119, N01WH32122, N01WH42107, N01WH42108, N01WH42109, N01WH42111, N01WH42112, N01WH42113, N01WH42114, N01WH42115, N01WH42116, N01WH42117, N01WH42118, N01WH42119, N01WH42120, N01WH42121, N01WH42122, N01WH42123, N01WH42124, N01WH42125, N01WH42126, N01WH42129, N01WH42130, N01WH42131, N01WH42132, N01WH44221] NR 37 TC 7 Z9 7 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-4197 EI 1573-6571 J9 J RELIG HEALTH JI J. Relig. Health PD MAR PY 2012 VL 51 IS 1 BP 20 EP 31 DI 10.1007/s10943-011-9549-6 PG 12 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA 958GS UT WOS:000305225100003 PM 22069057 ER PT J AU Trevino, KM Archambault, E Schuster, J Richardson, P Moye, J AF Trevino, Kelly M. Archambault, Elizabeth Schuster, Jennifer Richardson, Peter Moye, Jennifer TI Religious Coping and Psychological Distress in Military Veteran Cancer Survivors SO JOURNAL OF RELIGION & HEALTH LA English DT Article DE Religious coping; Cancer survivor; Veteran; Psychological distress ID BECK-DEPRESSION-INVENTORY; POSTTRAUMATIC-STRESS-DISORDER; QUALITY-OF-LIFE; BREAST-CANCER; PRIMARY-CARE; MEDICAL OUTPATIENTS; CIVILIAN VERSION; PTSD CHECKLIST; HEALTH; ADJUSTMENT AB Research on the relationship between religious coping and psychological wellbeing in cancer survivors is limited. Forty-eight veteran cancer survivors completed measures of psychological distress, posttraumatic growth, and positive and negative religious coping. Negative religious coping was associated with greater distress and growth. Positive religious coping was associated with greater growth. Gender, race, and religious affiliation were significant predictors of positive and negative religious coping. Veteran cancer survivors who utilize negative religious coping may benefit from referral to clergy or a mental health professional. Assessment of religious coping may be particularly important for female, non-White, and Christian cancer survivors. C1 [Trevino, Kelly M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Archambault, Elizabeth] VA Boston Healthcare Syst, Geriatr Mental Hlth, Brockton, MA USA. [Schuster, Jennifer] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Richardson, Peter] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. RP Trevino, KM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave,SM 271, Boston, MA 02215 USA. EM trevino.kelly@gmail.com RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU RRD VA [I01 RX000104] NR 48 TC 12 Z9 12 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-4197 J9 J RELIG HEALTH JI J. Relig. Health PD MAR PY 2012 VL 51 IS 1 BP 87 EP 98 DI 10.1007/s10943-011-9526-0 PG 12 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA 958GS UT WOS:000305225100008 PM 21822744 ER PT J AU Kaleyias, J Manley, P Kothare, SV AF Kaleyias, Joseph Manley, Peter Kothare, Sanjeev V. TI Sleep Disorders in Children With Cancer SO SEMINARS IN PEDIATRIC NEUROLOGY LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; EXCESSIVE DAYTIME SLEEPINESS; CENTRAL-NERVOUS-SYSTEM; QUALITY-OF-LIFE; PRACTICE PARAMETERS; CIRCADIAN-RHYTHMS; CHILDHOOD-CANCER; WAKEFULNESS TEST; ADULT SURVIVORS; FATIGUE AB Approximately three-fourths of all pediatric cancer patients will be long-term survivors; however, there can be a steep cost for cancer survivorship. Cancer treatment involves exposure to chemotherapy, surgical intervention, and radiation, which can cause lasting long-term toxicities. Children with brain tumors have the highest prevalence of long-term morbidities. These effects can be attributed to direct neurologic damage to the developing brain caused by tumor, hydrocephalus, surgical removal of the tumor, and the effects of irradiation. The late effects experienced by childhood cancer survivors involve multiple domains, one of which is sleep disorders. Sleep dysfunction has an increased prevalence in the pediatric cancer survivor population. These issues are disruptive to patients and cause a decrease in quality of life. This review focuses on sleep disorders that occur in pediatric cancer survivors and discusses the possible causes, the assessments used to determine specific sleep disorders, and treatment modalities used to ameliorate this dysfunction with the hope of improving patient's quality of life. Semin Pediatr Neurol 19:25-34 (C) 2012 Elsevier Inc. All rights reserved. C1 [Kothare, Sanjeev V.] Childrens Hosp, Pediat Sleep Med Training Program, Ctr Pediat Sleep Disorders, Div Epilepsy & Clin Neurophysiol,Dept Neurol, Boston, MA 02115 USA. [Manley, Peter] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kaleyias, Joseph] Med Sch Patras, Dept Pediat, Div Pediat Neurol, Patras, Greece. RP Kothare, SV (reprint author), Childrens Hosp, Pediat Sleep Med Training Program, Ctr Pediat Sleep Disorders, Div Epilepsy & Clin Neurophysiol,Dept Neurol, Fegan 9,300 Longwood Ave, Boston, MA 02115 USA. EM sanjeev.kothare@childrens.harvard.edu OI Kothare, Sanjeev/0000-0001-7849-6649 NR 67 TC 9 Z9 10 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1071-9091 EI 1558-0776 J9 SEMIN PEDIATR NEUROL JI Semin. Pediatr. Neurol. PD MAR PY 2012 VL 19 IS 1 BP 25 EP 34 DI 10.1016/j.spen.2012.02.013 PG 10 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 958TP UT WOS:000305263900005 PM 22641073 ER PT J AU Ullrich, NJ Embry, L AF Ullrich, Nicole J. Embry, Leanne TI Neurocognitive Dysfunction in Survivors of Childhood Brain Tumors SO SEMINARS IN PEDIATRIC NEUROLOGY LA English DT Review ID QUALITY-OF-LIFE; CENTRAL-NERVOUS-SYSTEM; LONG-TERM SURVIVORS; CONFORMAL RADIATION-THERAPY; CANCER SURVIVOR; COGNITIVE FUNCTION; ADULT SURVIVORS; DEVELOPMENTAL MODEL; CHILDRENS ONCOLOGY; PEDIATRIC-PATIENTS AB Newer treatments have resulted in increasing numbers of survivors of childhood cancer, for whom neurological and neurocognitive toxicity directly impacts overall functioning and quality of life. There are multiple disease- and host-related factors that influence the development of cancer-related neurocognitive dysfunction, which can progress over time and lead to significant functional impairments. This article provides an overview of the types of neurocognitive deficits seen in survivors of childhood brain tumors, the tools used to assess neurocognitive function, and the factors that impact its severity. This provides a framework for consideration of potential areas for primary prevention by reducing treatment-related toxicity as well as interventions, using behavioral and pharmacologic treatments. Semin Pediatr Neurol 19:35-42 (C) 2012 Elsevier Inc. All rights reserved. C1 [Ullrich, Nicole J.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Ullrich, Nicole J.] Dana Farber Canc Inst, Pediat Brain Tumor Program, Boston, MA 02115 USA. [Embry, Leanne] Univ Texas Hlth Sci Ctr, San Antonio, TX USA. RP Ullrich, NJ (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM nicole.ullrich@childrens.harvard.edu NR 59 TC 15 Z9 16 U1 2 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1071-9091 EI 1558-0776 J9 SEMIN PEDIATR NEUROL JI Semin. Pediatr. Neurol. PD MAR PY 2012 VL 19 IS 1 BP 35 EP 42 DI 10.1016/j.spen.2012.02.014 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 958TP UT WOS:000305263900006 PM 22641074 ER PT J AU Chen, YQ Hu, N Cheng, SC Musoke, P Zhao, LP AF Chen, Ying Qing Hu, Nan Cheng, Su-Chun Musoke, Philippa Zhao, Lue Ping TI Estimating Regression Parameters in an Extended Proportional Odds Model SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Counting process; Estimating function; HIV/AIDS; Maximum likelihood estimation; Semiparametric model; Time-varying covariate ID SEMIPARAMETRIC TRANSFORMATION MODELS; CENSORED-DATA; EFFICIENT ESTIMATION; INFERENCE; HAZARDS; TRANSMISSION; HIVNET-012; NEVIRAPINE; HIV-1 AB The proportional odds model may serve as a useful alternative to the Cox proportional hazards model to study association between covariates and their survival functions in medical studies. In this article, we study an extended proportional odds model that incorporates the so-called "external" time-varying covariates. In the extended model, regression parameters have a direct interpretation of comparing survival functions, without specifying the baseline survival odds function. Semiparametric and maximum likelihood estimation procedures are proposed to estimate the extended model. Our methods are demonstrated by Monte Carlo simulations, and applied to a landmark randomized clinical trial of a short-course nevirapine (NVP) for mother-to-child transmission (MTCT) of human immunodeficiency virus type-1 (HIV-1). Additional application includes an analysis of the well-known Veterans Administration (VA) lung cancer trial. C1 [Hu, Nan] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT 84132 USA. [Cheng, Su-Chun] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Musoke, Philippa] Makerere Univ, Dept Paediat & Child Hlth, Kampala, Uganda. EM yqchen@fhcrc.org; nan.hu@hci.utah.edu; scheng@jimmy.harvard.edu; pmusoke@mujhu.org; lzhao@fhcrc.org FU National Institute of Allergy and Infectious Diseases (NIH/NIAID) [R01 AI089341, R01 AI78835]; National Cancer Institute (NIH/NCI) [P01 CA053996, R01 CA 119225]; University of Utah's Study Design and Biostatistics Center; National Center for Research Resources [UL1-RR025764, C06-RR11234]; National Institute of Mental Health (NIH/NIMH) [R01 MH 084621] FX Ying Qing Chen is Full Member, Program in Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 (E-mail: yqchen@fhcrc.org). Nan Hu is Assistant Professor, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT 84132 nan.hu@hci.utah.edu). Su-Chun Cheng is Senior Research Scientist, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115 (E-mail: scheng@jimmy.harvard.edu). Philippa Musoke is Associate Professor, Department of Paediatrics and Child Health, Makerere University, Kampala, Uganda (E-mail: pmusoke@mujhu.org). Lue Ping Zhao is Full Member, Program in Biostatistics and Biomathematics, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 (E-mail: Izhaa@fhcrc.org). Chen's research was partially supported by grants from the National Institute of Allergy and Infectious Diseases (NIH/NIAID R01 AI089341, R01 AI78835) and the National Cancer Institute (NIH/NCI P01 CA053996), Hu's research was partially supported by the University of Utah's Study Design and Biostatistics Center, with funding in part from the Public Health Services research grant numbers UL1-RR025764 and C06-RR11234 and from the National Center for Research Resources, and Zhao's research was partially supported by grants from the National Institute of Mental Health (NIH/NIMH R01 MH 084621) and the National Cancer Institute (NIH/NCI R01 CA 119225). The authors thank the editor, an associate editor, and two referees for their valuable comments that helped improve a previous version of the article. NR 31 TC 2 Z9 2 U1 0 U2 4 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 EI 1537-274X J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2012 VL 107 IS 497 BP 318 EP 330 DI 10.1080/01621459.2012.656021 PG 13 WC Statistics & Probability SC Mathematics GA 951QN UT WOS:000304735200026 PM 22904583 ER PT J AU Tang, CY Eaves, E Dams-O'Connor, K Ho, L Leung, E Wong, E Carpenter, D Ng, J Gordon, W Pasinetti, G AF Tang, Cheuk Ying Eaves, Emily Dams-O'Connor, Kristen Ho, Lap Leung, Eric Wong, Edmund Carpenter, David Ng, Johnny Gordon, Wayne Pasinetti, Giulio TI DIFFUSE DISCONNECTIVITY IN TBI: A RESTING STATE FMRI AND DTI STUDY SO TRANSLATIONAL NEUROSCIENCE LA English DT Article DE Traumatic Brain Injury (TBI); Functional magnetic resonance imaging (fMRI); DTI; Cognitive Function ID TRAUMATIC BRAIN-INJURY; DEFAULT-MODE NETWORK; LATE-LIFE DEPRESSION; AXONAL INJURY; WORKING-MEMORY; FUNCTIONAL CONNECTIVITY; ALZHEIMERS-DISEASE; MRI; TASK; ABNORMALITIES AB Diffuse axonal injury is a common pathological consequence of Traumatic Brain Injury (TBI). Diffusion Tensor Imaging is an ideal technique to study white matter integrity using the Fractional Anisotropy (FA) index which is a measure of axonal integrity and coherence. There have been several reports showing reduced FA in individuals with TBI, which suggest demyelination or reduced fiber density in white matter tracts secondary to injury. Individuals with TBI are usually diagnosed with cognitive deficits such as reduced attention span, memory and executive function. In this study we sought to investigate correlations between brain functional networks, white matter integrity, and TBI severity in individuals with TBI ranging from mild to severe. A resting state functional magnetic resonance imaging protocol was used to study the default mode network in subjects at rest. FA values were decreased throughout all white matter tracts in the mild to severe TBI subjects. FA values were also negatively correlated with TBI injury severity ratings. The default mode network showed several brain regions in which connectivity measures were higher among individuals with TBI relative to control subjects. These findings suggest that, subsequent to TBI, the brain may undergo adaptation responses at the cellular level to compensate for functional impairment due to axonal injury. C1 [Tang, Cheuk Ying; Eaves, Emily; Leung, Eric; Wong, Edmund; Carpenter, David; Ng, Johnny] Mt Sinai Sch Med, Dept Radiol, New York, NY 10029 USA. [Tang, Cheuk Ying; Pasinetti, Giulio] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Dams-O'Connor, Kristen; Gordon, Wayne] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. [Pasinetti, Giulio] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Pasinetti, Giulio] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Tang, CY (reprint author), Mt Sinai Sch Med, Dept Radiol, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU National Center for Research Resources (NCRR), National Institutes of Health (NIH) [UL1RR029887] FX The study was supported by discretionary funding to GMP and Grant Number #UL1RR029887, National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The authors would also like to thank the Image Analysis Core of the Mount Sinai Translational and Molecular Imaging Institute. NR 38 TC 16 Z9 18 U1 1 U2 11 PU VERSITA PI WARSAW PA SOLIPSKA 14A-1, 02-482 WARSAW, POLAND SN 2081-3856 J9 TRANSL NEUROSCI JI Transl. Neurosci. PD MAR PY 2012 VL 3 IS 1 BP 9 EP 14 DI 10.2478/s13380-012-0003-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 951CN UT WOS:000304698400002 PM 23459252 ER PT J AU Sharma, NS Jindal, R Mitra, B Lee, S Li, LL Maguire, TJ Schloss, R Yarmush, ML AF Sharma, Nripen S. Jindal, Rohit Mitra, Bhaskar Lee, Serom Li, Lulu Maguire, Tim J. Schloss, Rene Yarmush, Martin L. TI Perspectives on Non-Animal Alternatives for Assessing Sensitization Potential in Allergic Contact Dermatitis SO CELLULAR AND MOLECULAR BIOENGINEERING LA English DT Article DE Immunobiology; Skin sensitization; In silico approaches; QSAR; 2D cell based models; 3D skin tissue models; Integrated Testing Strategies; Microfabrication; Microfluidics ID LYMPH-NODE ASSAY; RECONSTRUCTED HUMAN EPIDERMIS; DENDRITIC CELL-LINE; INSULT PATCH TEST; TEST H-CLAT; IN-VITRO; SKIN SENSITIZATION; LANGERHANS CELLS; STRATUM-CORNEUM; QSAR MODELS AB Skin sensitization remains a major environmental and occupational health hazard. Animal models have been used as the gold standard method of choice for estimating chemical sensitization potential. However, a growing international drive and consensus for minimizing animal usage have prompted the development of in vitro methods to assess chemical sensitivity. In this paper, we examine existing approaches including in silico models, cell and tissue based assays for distinguishing between sensitizers and irritants. The in silico approaches that have been discussed include Quantitative Structure Activity Relationships (QSAR) and QSAR based expert models that correlate chemical molecular structure with biological activity and mechanism based read-across models that incorporate compound electrophilicity. The cell and tissue based assays rely on an assortment of mono and coculture cell systems in conjunction with 3D skin models. Given the complexity of allergen induced immune responses, and the limited ability of existing systems to capture the entire gamut of cellular and molecular events associated with these responses, we also introduce a microfabricated platform that can capture all the key steps involved in allergic contact sensitivity. Finally, we describe the development of an integrated testing strategy comprised of two or three tier systems for evaluating sensitization potential of chemicals. C1 [Sharma, Nripen S.; Jindal, Rohit; Mitra, Bhaskar; Lee, Serom; Li, Lulu; Maguire, Tim J.; Schloss, Rene; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08854 USA. [Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd,231 Piscataway, Piscataway, NJ 08854 USA. EM yarmush@rci.rutgers.edu FU NIBIB NIH HHS [P41 EB002503]; NIGMS NIH HHS [T32 GM008339] NR 170 TC 1 Z9 2 U1 0 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1865-5025 J9 CELL MOL BIOENG JI Cell. Mol. Bioeng. PD MAR PY 2012 VL 5 IS 1 BP 52 EP 72 DI 10.1007/s12195-011-0189-4 PG 21 WC Cell & Tissue Engineering; Biophysics; Cell Biology SC Cell Biology; Biophysics GA 940EJ UT WOS:000303872500005 PM 24741377 ER PT J AU Hahn, JO Reisner, AT Jaffer, FA Asada, HH AF Hahn, Jin-Oh Reisner, Andrew T. Jaffer, Farouc A. Asada, H. Harry TI Subject-Specific Estimation of Central Aortic Blood Pressure Using an Individualized Transfer Function: A Preliminary Feasibility Study SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE Cardiovascular monitoring; central aortic blood pressure; individualized transfer function (ITF) ID PERIPHERAL ARTERIAL-PRESSURE; WAVE-FORM; PULSE; VALIDATION; EXERCISE; TIME; HYPERTENSION; DERIVATION; REST AB This paper presents a new approach to the estimation of unknown central aortic blood pressure waveform from a directly measured peripheral blood pressure waveform, in which a physics-based model is employed to solve for a subject-and state-specific individualized transfer function (ITF). The ITF provides the means to estimate the unknown central aortic blood pressure from the peripheral blood pressure. Initial proof-of-principle for the ITF is demonstrated experimentally through an in vivo protocol. In swine subjects taken through wide range of physiologic conditions, the ITF was on average able to provide central aortic blood pressure waveforms more accurately than a nonindividualized transfer function. Its usefulness was most evident when the subject's pulse transit time deviated from normative values. In these circumstances, the ITF yielded statistically significant reductions over a nonindividualized transfer function in the following three parameters: 1) 30% reduction in the root-mean-squared error between estimated versus actual central aortic blood pressure waveform (p < 10(-4)), 2) >50% reduction in the error between estimated versus actual systolic and pulse pressures (p < 10(-4)), and 3) a reduction in the overall breakdown rate (i.e., the frequency of estimation errors >3 mmHg, p < 10(-4)). In conclusion, the ITF may offer an attractive alternative to existing methods that estimates the central aortic blood pressure waveform, and may be particularly useful in nonnormative physiologic conditions. C1 [Hahn, Jin-Oh] Univ Alberta, Dept Mech Engn, Edmonton, AB T6G 2G8, Canada. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02142 USA. [Reisner, Andrew T.; Jaffer, Farouc A.] Harvard Univ, Sch Med, Boston, MA 02142 USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02142 USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02142 USA. [Asada, H. Harry] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Hahn, JO (reprint author), Univ Alberta, Dept Mech Engn, Edmonton, AB T6G 2G8, Canada. EM jinoh.hahn@alum.mit.edu; areisner@partners.org; fjaffer@mgh.harvard.edu; asada@mit.edu OI Jaffer, Farouc/0000-0001-7980-384X NR 28 TC 12 Z9 12 U1 2 U2 14 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1089-7771 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD MAR PY 2012 VL 16 IS 2 SI SI BP 212 EP 220 DI 10.1109/TITB.2011.2177668 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 943WZ UT WOS:000304158600005 PM 22147332 ER PT J AU Frakt, AB Pizer, SD Feldman, R AF Frakt, Austin B. Pizer, Steven D. Feldman, Roger TI The Effects of Market Structure and Payment Rate on the Entry of Private Health Plans into the Medicare Market SO INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING LA English DT Article ID RAISING RIVALS COSTS; INSTRUMENTAL VARIABLES; HMO PARTICIPATION; INSURANCE MARKETS; MANAGED CARE; INDUSTRY; MODEL; POWER; RISK; BENEFICIARIES AB Private insurance firms participating in Medicare can offer up to three principal plan types: coordinated care plans (CCPs), prescription drug plans (PDPs), and private fee-for-service (FEES) plans. Firms can make entry and marketing decisions separately across plan types and geographic regions. In this study, we estimate firm-level models of Medicare private plan entry using data from the years 2007 to 2009. Our models include a measure of market structure and separately identify CCP, PDP, and PFFS entry. We find evidence that entry barriers associated with CCP market concentration affect three product types. We also find evidence of cross-product competition and common cost or demand factors that make entry with certain product combinations more likely. We predict that the market presence of CCPs and PFFS plans will decrease and that of PDPs will increase in response to payment reductions included in the new health reform law. C1 [Frakt, Austin B.; Pizer, Steven D.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Frakt, Austin B.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Pizer, Steven D.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Feldman, Roger] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. RP Frakt, AB (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,Mail Stop 152H, Boston, MA 02130 USA. EM frakt@bu.edu NR 83 TC 4 Z9 4 U1 2 U2 10 PU BLUE CROSS BLUE SHIELD ASSOC PI ROCHESTER PA 150 EAST MAIN ST, ROCHESTER, NY 14647 USA SN 0046-9580 EI 1945-7243 J9 INQUIRY-J HEALTH CAR JI Inquiry-J. Health Care Organ. Provis. Financ. PD SPR PY 2012 VL 49 IS 1 BP 15 EP 36 DI 10.5034/inquiryjrnl_49.01.03 PG 22 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 942UR UT WOS:000304075900003 PM 22650015 ER PT J AU Duong, TQ AF Duong, Timothy Q. TI Multimodal MRI of Experimental Stroke SO TRANSLATIONAL STROKE RESEARCH LA English DT Review DE MRI; Perfusion-diffusion mismatch; ADC; CBF; DWI; PWI; Experimental stroke model; Rodents; Oxygen challenge; Predictive mode; Magnetic resonance imaging; Rats; Hyperperfusion; fMRI ID CEREBRAL-BLOOD-FLOW; ISCHEMIC TISSUE-FATE; APPARENT DIFFUSION-COEFFICIENT; QUANTITATIVE PERFUSION; POSTISCHEMIC HYPERPERFUSION; PLASMINOGEN ACTIVATOR; ARTERY OCCLUSION; FOCAL ISCHEMIA; BRAIN-INJURY; RAT-BRAIN AB Stroke is the fourth leading cause of death and the leading cause of long-term disability in USA. Brain imaging data from experimental stroke models and stroke patients have shown that there is often a gradual progression of potentially reversible ischemic injury toward infarction. Reestablishing tissue perfusion and/or treating with neuroprotective drugs in a timely fashion are expected to salvage some ischemic tissues. Diffusion-weighted imaging based on magnetic resonance imaging (MRI) in which contrast is based on water motion can detect ischemic injury within minutes after onsets, whereas computed tomography and other imaging modalities fail to detect stroke injury for at least a few hours. Along with quantitative perfusion imaging, the perfusion-diffusion mismatch which approximates the ischemic penumbra could be imaged noninvasively. This review describes recent progresses in the development and application of multimodal MRI and image analysis techniques to study ischemic tissue at risk in experimental stroke in rats. C1 [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Dept Vet Affairs, S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Duong, Timothy Q.] SW Fdn Biomed Res, SW Natl Primate Res Ctr, San Antonio, TX 78284 USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, Dept Ophthalmol, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008 FU NINDS NIH HHS [R01 NS045879] NR 67 TC 5 Z9 5 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 J9 TRANSL STROKE RES JI Transl. Stroke Res. PD MAR PY 2012 VL 3 IS 1 SI SI BP 8 EP 15 DI 10.1007/s12975-011-0140-y PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 943YP UT WOS:000304164300003 PM 24323751 ER PT J AU Wey, HY Duong, TQ AF Wey, Hsiao-Ying Duong, Timothy Q. TI Multimodal MRI of Nonhuman Primate Stroke SO TRANSLATIONAL STROKE RESEARCH LA English DT Review DE Nonhuman primate; MRI; Perfusion; Diffusion; Functional MRI; MCAO ID FOCAL CEREBRAL-ISCHEMIA; APPARENT DIFFUSION-COEFFICIENT; TRANSORBITAL BABOON MODEL; PERFUSION MRI; REPERFUSED STROKE; ARTERY OCCLUSION; WATER DIFFUSION; RHESUS-MONKEYS; BRAIN ISCHEMIA; TISSUE SODIUM AB Stroke is the fourth leading cause of death. Despite decades of research, no neuroprotective drug has proven to be effective clinically. One widely accepted view to account for this negative outcome is that the rodent stroke model simply does not adequately reflect the complexity of human stroke. Recent failures of several high-profile neuroprotective drugs for stroke treatment in phase III clinical trials further under-score the importance of developing adequate animal models for stroke research. The brain organization and vascular circuitry of nonhuman primates (NHPs) are more homologous with humans than the widely used rodent for stroke modeling. The Stroke Therapy Academic Industry Roundtable, a national committee commissioned by the American Heart Association, recommended that clinically relevant NHP stroke models be established for developing and assessing neuroprotective drugs. The aim of this article is to review the challenges and applications of magnetic resonance imaging studies of NHP stroke models. C1 [Wey, Hsiao-Ying; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Wey, Hsiao-Ying] Harvard Univ, Sch Med, Dept Radiol,Massachussetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Wey, Hsiao-Ying; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM wey@nmr.mgh.harvard.edu; duongt@uthscsa.edu RI Duong, Timothy/B-8525-2008; Wey, Hsiao-Ying/G-3031-2012 FU American Heart Association [0940104N, 11PRE5670005]; National Institute of Health (NINDS) [R01 NS45879]; Clinical Translational Science Award [UL1RR025767]; Institute for Integration of Medicine and Science, University of Texas Health Science Center FX This work was supported by the American Heart Association Established Investigator Award 0940104N, National Institute of Health (NINDS R01 NS45879) and Clinical Translational Science Award's imaging supplement (parent grant UL1RR025767) to TQD. HYW was supported by a predoctoral fellowship (11PRE5670005) from the American Heart Association and by a Translational Science Training Grant from the Institute for Integration of Medicine and Science, University of Texas Health Science Center. NR 47 TC 1 Z9 1 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1868-4483 J9 TRANSL STROKE RES JI Transl. Stroke Res. PD MAR PY 2012 VL 3 IS 1 SI SI BP 84 EP 89 DI 10.1007/s12975-012-0145-1 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 943YP UT WOS:000304164300011 PM 24323756 ER PT J AU Lynch, J Lathan, CL AF Lynch, J. Lathan, C. L. TI DIFFUSION OF THE EGFR ASSAY IN UNITED STATES SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 10th International Symposium on Targeted Anticancer Therapies CY MAR 08-10, 2012 CL Amsterdam, NETHERLANDS C1 [Lynch, J.; Lathan, C. L.] Univ Massachusetts, Dana Farber Canc Inst, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2012 VL 23 SU 1 BP 37 EP 38 PG 2 WC Oncology SC Oncology GA 940CH UT WOS:000303867100096 ER PT J AU Wen, LS Geduld, HI Nagurney, JT Wallis, LA AF Wen, Leana S. Geduld, Heike I. Nagurney, J. Tobias Wallis, Lee A. TI Perceptions of graduates from Africa's first emergency medicine training program at the University of Cape Town/Stellenbosch University SO CANADIAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE internatonal emergency medicine; medical education; residency; South Africa ID DEPARTMENTS AB Objective: Africa's first postgraduate training program in emergency medicine (EM) was established at the University of Cape Town/Stellenbosch University (UCT/SUN) in 2004. This study of the UCT/SUN EM program investigated the backgrounds, perceptions, and experiences of its graduates. Methods: This was a cross-sectional descriptive study. The study population was the 30 graduates from the first four classes in the UCT/SUN EM program (2007-2010). We employed a scripted interview with a combination of closed and open-ended questions. Data were analyzed using the thematic method of qualitative analysis. Results: Twenty-seven (90%) graduates were interviewed. Initial career goals were primarily (78%) to practice EM in a nonacademic clinical capacity. At the time of the interview, 52% held academic positions, 15% had nonacademic clinical positions, and 33% had temporary positions and were looking for other posts. The three most commonly cited strengths of their program were diversity of clinical rotations (85%), autonomy and procedural experience (63%), and importance of being pioneers within Africa (52%). The three most commonly cited weaknesses were lack of bedside teaching in the ED (96%), lack of career options after graduation (74%), and lack of preparation for academic careers (70%). Conclusions: The lessons identified from structured interviews with graduates from Africa's first EM training include the importance of strong clinical training, difficulty of ensuring bedside teaching in a new program, the necessity of ensuring postgraduation positions, and the need for academic training. These findings may be useful for other developing countries looking to start EM training programs. C1 [Wen, Leana S.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Emergency Med, Harvard Affiliated Emergency Med Residency, Boston, MA 02115 USA. [Geduld, Heike I.; Wallis, Lee A.] Univ Cape Town, Div Emergency Med, ZA-7925 Cape Town, South Africa. [Geduld, Heike I.; Wallis, Lee A.] Univ Stellenbosch, Div Emergency Med, ZA-7600 Stellenbosch, South Africa. RP Wen, LS (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Emergency Med, Harvard Affiliated Emergency Med Residency, 75 Francis St,Neville House 236-A, Boston, MA 02115 USA. EM Wen.Leana@gmail.com FU Partners Healthcare FX Dr. Wen received a travel grant from Partners Healthcare. NR 15 TC 2 Z9 2 U1 0 U2 5 PU DECKER PUBL INC PI HAMILTON PA 69 JOHN ST S, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1481-8035 J9 CAN J EMERG MED JI Can. J. Emerg. Med. PD MAR PY 2012 VL 14 IS 2 BP 97 EP 105 DI 10.2310/8000.2012.110639 PG 9 WC Emergency Medicine SC Emergency Medicine GA 940QC UT WOS:000303907100006 PM 22554441 ER PT J AU Hoy, CL Everett, WN Yildirim, M Kobler, J Zeitels, SM Ben-Yakar, A AF Hoy, Christopher L. Everett, W. Neil Yildirim, Murat Kobler, James Zeitels, Steven M. Ben-Yakar, Adela TI Towards endoscopic ultrafast laser microsurgery of vocal folds SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE ultrafast lasers; femtosecond laser surgery; second-harmonic generation; endoscope; nonlinear optics; multiphoton process; laser-induced damage ID MULTIPHOTON MICROSCOPY; SURGERY; LARYNGOLOGY; PROBE AB Vocal fold scarring is a predominant cause of voice disorders yet lacks a reliable treatment method. The injection of soft biomaterials to improve mechanical compliance of the vocal folds has emerged as a promising treatment. Here, we study the use of precise femtosecond laser microsurgery to ablate subsurface voids, with a goal of eventually creating a plane in dense subepithelial scar tissue into which biomaterials can be injected for their improved localization. Specifically, we demonstrate the ablation of small subepithelial voids in porcine vocal fold tissue up to 120 mu m below the surface such that larger voids in the active area of vocal fold mucosa (similar to 3 x 10 mm(2)) can eventually be ablated in about 3 min. We use sub-mu J, 776-nm pulses from a compact femtosecond fiber laser system operating at a 500-kHz repetition rate. The use of relatively high repetition rates, with a small number of overlapping pulses, is critical to achieving ablation in a very short time while still avoiding significant heat deposition. Additionally, we use the same laser for nonlinear optical imaging to provide visual feedback of tissue structure and to confirm successful ablation. The ablation parameters, including pulse duration, pulse energy, spot size, and scanning speed, are comparable to the specifications in our recently developed miniaturized femtosecond laser surgery probes, illustrating the feasibility of developing an ultrafast laser surgical instrument. 2072 Society of Photooptical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.3.038002] C1 [Hoy, Christopher L.; Everett, W. Neil; Yildirim, Murat; Ben-Yakar, Adela] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Kobler, James; Zeitels, Steven M.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Ben-Yakar, A (reprint author), Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. EM ben-yakar@mail.utexas.edu RI Hoy, Christopher/H-5004-2013 OI Hoy, Christopher/0000-0002-4567-6958 FU National Science Foundation [IDR: CBET-1014953, CBET-0846868]; Texas Ignition Fund FX This work was supported by grants from the National Science Foundation (IDR: CBET-1014953 and Career Award: CBET-0846868) and a grant from the Texas Ignition Fund. The authors would like to thank Raydiance, Inc. for use of their Discovery fiber laser, as well as Dr. R. Rox Anderson and Dr. Nicholas Durr for consultation. NR 20 TC 8 Z9 8 U1 0 U2 8 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR PY 2012 VL 17 IS 3 AR 038002 DI 10.1117/1.JBO.17.3.038002 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 937XJ UT WOS:000303697000032 PM 22502583 ER PT J AU Wang, TY Mancuso, JJ Sapozhnikova, V Dwelle, J Ma, LL Willsey, B Kazmi, SMS Qiu, JZ Li, XK Asmis, R Johnston, KP Feldman, MD Milner, TE AF Wang, Tianyi Mancuso, J. Jacob Sapozhnikova, Veronika Dwelle, Jordan Ma, Li L. Willsey, Brian Kazmi, S. M. Shams Qiu, Jinze Li, Xiankai Asmis, Reto Johnston, Keith P. Feldman, Marc D. Milner, Thomas E. TI Dual-wavelength multifrequency photothermal wave imaging combined with optical coherence tomography for macrophage and lipid detection in atherosclerotic plaques using gold nanoparticles SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE atherosclerosis; macrophage; lipid; nanorose; photothermal wave imaging; optical coherence tomography; two-photon luminescence microscopy ID CENTRAL-NERVOUS-SYSTEM; IRON-OXIDE; MAGNETIC-RESONANCE; CORONARY PLAQUE; IN-VITRO; CELLS; EXPRESSION; INFLAMMATION; MICROSCOPY; RUPTURE AB The objective of this study was to assess the ability of combined photothermal wave (PTW) imaging and optical coherence tomography (OCT) to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanorose as a contrast agent) and lipid deposits in atherosclerotic plaques. Aortas with atherosclerotic plaques were harvested from nine male New Zealand white rabbits divided into nanorose- and saline-injected groups and were imaged by dual-wavelength (800 and 1210 nm) multifrequency (0.1, 1 and 4 Hz) PTW imaging in combination with OCT. Amplitude PTW images suggest that lateral and depth distribution of nanorose-loaded macrophages (confirmed by two-photon luminescence microscopy and RAM-11 macrophage stain) and lipid deposits can be identified at selected modulation frequencies. Radiometric temperature increase and modulation amplitude of superficial nanoroses in response to 4 Hz laser irradiation (800 nm) were significantly higher than native plaque (P < 0.001). Amplitude PTW images (4 Hz) were merged into a coregistered OCT image, suggesting that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques (P < 0.001) at edges of lipid deposits. Results suggest that combined PTW-OCT imaging can simultaneously reveal plaque structure and composition, permitting characterization of nanorose-loaded macrophages and lipid deposits in atherosclerotic plaques. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.3.036009] C1 [Wang, Tianyi; Dwelle, Jordan; Kazmi, S. M. Shams; Qiu, Jinze; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Ma, Li L.; Willsey, Brian; Johnston, Keith P.] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. [Mancuso, J. Jacob; Sapozhnikova, Veronika; Li, Xiankai; Asmis, Reto; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Div Cardiol, San Antonio, TX 78229 USA. [Feldman, Marc D.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Milner, TE (reprint author), Univ Texas Austin, Dept Biomed Engn, 1 Univ Stn,C0800, Austin, TX 78712 USA. EM terra.laser@gmail.com RI Qiu, Jinze /I-2272-2013 OI Qiu, Jinze /0000-0001-8466-1460 FU Veterans Administration; Welch Foundation [F-1319]; NSF [CBET-0968038]; Department of Energy Center for Frontiers of Subsurface Energy Security FX The authors would like to acknowledge the technical support from the University of Texas Health Science Center at San Antonio. This work was supported by a Veterans Administration merit grant to Feldman, a Welch Foundation grant F-1319 and NSF grant CBET-0968038 to Johnston, and the Department of Energy Center for Frontiers of Subsurface Energy Security. NR 59 TC 6 Z9 6 U1 1 U2 12 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR PY 2012 VL 17 IS 3 AR 036009 DI 10.1117/1.JBO.17.3.036009 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 937XJ UT WOS:000303697000016 PM 22502567 ER PT J AU Zettergren, E Vickers, D Runnels, J Murthy, SK Lin, CP Niedre, M AF Zettergren, Eric Vickers, Dwayne Runnels, Judith Murthy, Shashi K. Lin, Charles P. Niedre, Mark TI Instrument for fluorescence sensing of circulating cells with diffuse light in mice in vivo SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE road image; diffuse; in vivo; flow cytometry; fluorescence ID METASTATIC BREAST-CANCER; TUMOR-CELLS; PERIPHERAL-BLOOD; DISEASE PROGRESSION; MULTIPLE-MYELOMA; FLOW-CYTOMETRY; MOUSE; SURVIVAL AB Accurate quantification of circulating cell populations in mice is important in many areas of preclinical biomedical research. Normally, this is done either by extraction and analysis of small blood samples or, more recently, by using microscopy-based in vivo fluorescence flow cytometry. We describe a new technological approach to this problem using detection of diffuse fluorescent light from relatively large blood vessels in vivo. The diffuse fluorescence flow cytometer (DFFC) uses a laser to illuminate a mouse limb and an array of optical fibers coupled to a high-sensitivity photomultiplier tube array operating in photon counting mode to detect weak fluorescence signals from cells. We first demonstrate that the DFFC instrument is capable of detecting fluorescent microspheres and Vybrant-DiD-labeled cells in a custom-made optical flow phantom with similar size, optical properties, linear flow rates, and autofluorescence as a mouse limb. We also present preliminary data demonstrating that the DFFC is capable of detecting circulating cells in nude mice in vivo. In principle, this device would allow interrogation of the whole blood volume of a mouse in minutes, with sensitivity improvement by several orders of magnitude compared to current approaches. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.3.037001] C1 [Zettergren, Eric; Vickers, Dwayne; Murthy, Shashi K.; Niedre, Mark] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. [Runnels, Judith; Lin, Charles P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Runnels, Judith; Lin, Charles P.] Harvard Univ, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Runnels, Judith; Lin, Charles P.] Wellman Ctr Photomed, Boston, MA 02114 USA. RP Niedre, M (reprint author), Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. EM mniedre@ece.neu.edu RI Vickers, Dwayne/I-5819-2012 OI Vickers, Dwayne/0000-0002-9218-7348 FU National Institutes of Health [R21 HL098750-01]; Northeastern University FX This work was funded with a grant from the National Institutes of Health (R21 HL098750-01) and from a Northeastern University laboratory startup grant. The assistance of Dr. Riikka Pastila and Tushar Swamy in conducting experiments is also gratefully acknowledged. NR 26 TC 7 Z9 7 U1 0 U2 9 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR PY 2012 VL 17 IS 3 AR 037001 DI 10.1117/1.JBO.17.3.037001 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 937XJ UT WOS:000303697000022 PM 22502573 ER PT J AU Ren, XF Akiyoshi, K Grafe, MR Vandenbark, AA Hurn, PD Herson, PS Offner, H AF Ren, Xuefang Akiyoshi, Kozaburo Grafe, Marjorie R. Vandenbark, Arthur A. Hurn, Patricia D. Herson, Paco S. Offner, Halina TI Myelin specific cells infiltrate MCAO lesions and exacerbate stroke severity SO METABOLIC BRAIN DISEASE LA English DT Article DE Experimental stroke; Myelin reactive splenocytes; Inflammatory responses; Neurologic deficit ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MURINE EXPERIMENTAL STROKE; FOCAL CEREBRAL-ISCHEMIA; GROWTH-FACTOR-BETA; BASIC-PROTEIN; T-CELLS; MULTIPLE-SCLEROSIS; IMMUNE PRIVILEGE; IMMUNOLOGICAL-TOLERANCE AB Although inflammatory responses increase stroke severity, the role of immune cells specific for central nervous system (CNS) antigens remains controversial. Disruption of the blood-brain barrier (BBB) during stroke allows CNS antigens to leak into the peripheral circulation and enhances access of circulating leukocytes to the brain, including those specific for CNS antigens such as myelin oligodendrocyte glycoprotein (MOG) that can induce experimental autoimmune encephalomyelitis (EAE). We here demonstrate for the first time that myelin reactive splenocytes specific for MOG transferred into severe combined immunodeficient (SCID) mice can migrate into the infarct hemisphere of recipients subjected to 60 min middle cerebral artery occlusion (MCAO) and 96 h reperfusion; moreover these cells exacerbate infarct volume and worsen neurological deficits compared to animals transferred with naive splenocytes. These findings indicate that autoimmunity in the CNS can exert detrimental injury on brain cells and worsen the damage from ischemic stroke. C1 [Ren, Xuefang; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Grafe, Marjorie R.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Dept Vet Affairs Med Ctr, Res Serv, Portland, OR USA. [Ren, Xuefang; Akiyoshi, Kozaburo; Grafe, Marjorie R.; Herson, Paco S.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. [Hurn, Patricia D.] Univ Texas Syst, Off Hlth Affairs, Austin, TX USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIH [NR03521, NS49210]; Collins Medical Trust; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX We thank Dr. Heng Hu, Dr. Sushmita Sinha, Dr. Sheetal Bodhankar, Dr. Suzan Dziennis, Dr. Takeru Shimizu and Ms. Sandhya Subramanian for helpful discussions; Ms. Xiao Jing Nie for performing histological staining and Ms. Lisa Miller for help with experiments; and Ms. Eva Niehaus for assistance in preparing the manuscript. This work was supported by NIH Grants NR03521 (PDH), NS49210 (PDH) and the Collins Medical Trust (XR). This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 44 TC 16 Z9 16 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD MAR PY 2012 VL 27 IS 1 BP 7 EP 15 DI 10.1007/s11011-011-9267-5 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 940BM UT WOS:000303865000002 PM 21989743 ER PT J AU Xin, JP Fargo, KN Tanzer, L Sanders, VM Jones, KJ AF Xin, Junping Fargo, Keith N. Tanzer, Lisa Sanders, Virginia M. Jones, Kathryn J. TI Immune cell-mediated neuroprotection is independent of estrogen action through estrogen receptor-alpha SO METABOLIC BRAIN DISEASE LA English DT Article DE Estrogen; CD4(+) T cell; Facial motoneuron; Axotomy; Neuroprotection ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REGULATORY T-CELLS; FACIAL MOTONEURON SURVIVAL; NERVE TRANSECTION; EXPRESSION; TESTOSTERONE; AXOTOMY; MICE; LYMPHOCYTES; CNS AB It has been well documented that both estrogen and immune cells (CD4(+) T cells) mediate neuroprotection in the mouse facial nerve axotomy model. Estrogen has been shown to play an important role in regulating the immune response. However, it is unclear whether immune cell-mediated neuroprotection is dependent on estrogen signaling. In this study, using FACS staining, we confirmed that the majority of CD4(+) T cells express high levels of estrogen receptor-alpha (ER alpha), suggesting that CD4(+) T cell-mediated neuroprotection may be modulated by estrogen signaling. We previously found that immunodeficient Rag-2KO mice showed a significant increase in axotomy-induced facial motoneuron death compared to immunocompetent wild-type mice. Therefore, we investigated axotomy-induced facial motoneuron loss in immunodeficient Rag-2KO mice that received 17 beta-estradiol treatment or adoptive transfer of immune cells from mice lacking functional ER alpha. Our results indicate that while estradiol treatment failed to rescue facial motoneurons from axotomy-induced cell death in Rag-2KO mice, immune cells lacking ERa successfully restored facial motoneuron survival in Rag-2 KO mice to a wild-type level. Collectively, we concluded that CD4(+) T cell-mediated neuroprotection is independent of estrogen action through ERa. C1 [Xin, Junping; Fargo, Keith N.; Tanzer, Lisa] Loyola Univ, Med Ctr, Inst Neurosci, Maywood, IL 60153 USA. [Xin, Junping; Fargo, Keith N.; Tanzer, Lisa] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res & Dev Serv, Hines, IL 60141 USA. [Sanders, Virginia M.] Ohio State Univ, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Jones, Kathryn J.] Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. RP Xin, JP (reprint author), Loyola Univ, Med Ctr, Inst Neurosci, 2160 S 1st Ave, Maywood, IL 60153 USA. EM neuroimmune@gmail.com FU National Institutes of Health [NS40433]; VA [RRD CDA-2 B6598-W]; Muscular Dystrophy Association [MDA202906] FX K.J.J. and V.M.S. were supported by National Institutes of Health grant NS40433, and K.N.F. was supported by VA grant RR&D CDA-2 B6598-W. J.X. was supported by Muscular Dystrophy Association grant (MDA202906). We thank Tom Alexander for technical support, as well as Linda Poggensee and Dr. Nichole Mesnard for their editorial assistance. NR 40 TC 1 Z9 2 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD MAR PY 2012 VL 27 IS 1 BP 23 EP 28 DI 10.1007/s11011-011-9265-7 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 940BM UT WOS:000303865000004 PM 21975535 ER PT J AU Subramanian, S Miller, LM Grafe, MR Vandenbark, AA Offner, H AF Subramanian, Sandhya Miller, Lisa M. Grafe, Marjorie R. Vandenbark, Arthur A. Offner, Halina TI Contribution of GPR30 for 1,25 dihydroxyvitamin D-3 protection in EAE SO METABOLIC BRAIN DISEASE LA English DT Article DE GPR30; EAE; 1,25 dihydroxyvitamin D-3; Estrogen ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; RECEPTOR; ACTIVATION; MICE AB Previous studies have demonstrated that vitamin D3-mediated protection in EAE occurs only in females and is dependent on the presence of diestrus levels of 17 beta-estradiol (E2). To evaluate the role of estrogen receptors in vitamin D3 treatment of EAE, we compared disease severity, CNS histopathology and immunological responses in vehicle and calcitrol (1,25 dihydroxyvitamin D-3) treated WT C57BL/6 mice vs. GPR30 membrane estrogen receptor (MER) knockout mice with MOG-35-55 peptide-induced EAE. Our results demonstrated that vitamin D-3-mediated prevention of clinical signs, CNS cellular lesions and demyelination observed in WT mice was abrogated in GPR30-KO mice with EAE. Regulatory effects of vitamin D-3 treatment that were MER dependent included increased levels of IL-10 and IL-6 secreted by MOG peptide-reactive splenocytes and increased expression of CCL5, CCR1 & CCR3 in spleen tissue. These results demonstrate for the first time that the MER is a key contributor to the E2-dependent effects of vitamin D-3-mediated protection in EAE. C1 [Subramanian, Sandhya; Miller, Lisa M.; Vandenbark, Arthur A.; Offner, Halina] Portland VA Med Ctr, Portland, OR 97239 USA. [Miller, Lisa M.; Vandenbark, Arthur A.; Offner, Halina] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Grafe, Marjorie R.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Dept Vet Affairs Med Ctr, Res Serv, Portland, OR 97239 USA. [Vandenbark, Arthur A.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. [Offner, Halina] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU National Multiple Sclerosis Society [RG3107-D-6]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX The authors wish to thank Ms. Eva Niehaus for assistance in preparing the manuscript. This work was supported by National Multiple Sclerosis Society grant RG3107-D-6. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 22 TC 8 Z9 9 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7490 J9 METAB BRAIN DIS JI Metab. Brain Dis. PD MAR PY 2012 VL 27 IS 1 BP 29 EP 35 DI 10.1007/s11011-011-9266-6 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 940BM UT WOS:000303865000005 PM 21994003 ER PT J AU Van den Stock, J de Gelder, B AF Van den Stock, Jan de Gelder, Beatrice TI Emotional information in body and background hampers recognition memory for faces SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE Context; Face; Emotion; Memory; Body; Scene ID FACIAL EXPRESSIONS; NEURAL MECHANISMS; PERCEPTION; RETRIEVAL; CONTEXT; INTEGRATION; VOICE AB Emotional influences on memory for events have long been documented yet surprisingly little is known about how emotional signals conveyed by contextual cues influence memory for face identity. This study investigated how positively and negatively valenced contextual emotion cues conveyed by body expressions or background scenes influence face memory. The results provide evidence of emotional context influence on face recognition memory and show that faces encoded in emotional (either fearful or happy) contexts (either the body or background scene) are less well recognized than faces encoded in neutral contexts and this effect is larger for body context than for scene context. The findings are compatible with the hypothesis that emotional signals in visual scenes trigger orienting responses which may lead to a less elaborate processing of featural details like the identity of a face, in turn resulting in a decreased facial recognition memory. (C) 2012 Elsevier Inc. All rights reserved. C1 [de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [de Gelder, Beatrice] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Van den Stock, Jan; de Gelder, Beatrice] Katholieke Univ Leuven, BELL, Div Psychiat, Dept Neurosci, Louvain, Belgium. [Van den Stock, Jan; de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. RP de Gelder, B (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Room 417,Bldg 36,1st St, Charlestown, MA 02129 USA. EM jan.vandenstock@med.kuleuven.be; degelder@nmr.mgh.harvard.edu RI Van den Stock, Jan/F-1906-2014 OI Van den Stock, Jan/0000-0001-5756-3195 FU European Commission (COBOL); FWO-Vlaanderen; FET-Open, COBOL FX We are grateful to two anonymous reviewers for their helpful suggestions. J.V.d.S. and B.d.G. are partly supported by European Commission (COBOL) Grant. J.V.d.S. is a post-doctoral researcher supported by FWO-Vlaanderen. B.d.G is partly supported by FP 6 FET-Open, COBOL Grant en FP7-FET-Open Grants. NR 28 TC 24 Z9 24 U1 1 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD MAR PY 2012 VL 97 IS 3 BP 321 EP 325 DI 10.1016/j.nlm.2012.01.007 PG 5 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 937ZM UT WOS:000303702700006 PM 22406473 ER PT J AU Taneja, R Bhargava, P Cuevas, C Dighe, MK AF Taneja, Ranu Bhargava, Puneet Cuevas, Carlos Dighe, Manjiri K. TI Common and Less-Common Renal Masses and Masslike Conditions SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Renal mass; Incidental renal mass; Genitourinary imaging; Kidney disease; Renal disease ID SOLITARY FIBROUS TUMOR; LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; UPPER URINARY-TRACT; IMAGING FINDINGS; CELL CARCINOMA; AUTOIMMUNE PANCREATITIS; PATHOLOGICAL CORRELATION; LYMPHOBLASTIC-LEUKEMIA; ACUTE PYELONEPHRITIS; MEDULLARY CARCINOMA AB As an increasing number of imaging examinations are performed, a greater number of incidental renal lesions are detected. Apart from the usual cysts and solid renal cell carcinomas, a variety of unusual benign and malignant renal lesions exist. Imaging is invaluable in characterizing these lesions and is confirmatory in some benign lesions. Renal cell carcinoma remains the diagnosis of exclusion; however, assessment of the imaging pattern in the appropriate clinical context can improve diagnostic accuracy. The objective of this article is to familiarize the radiologist with the imaging appearance of unusual non-neoplastic and neoplastic lesions and correlate with histopathologic studies when available. C1 [Bhargava, Puneet] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA 98108 USA. [Taneja, Ranu] Changi Gen Hosp, Dept Radiol, Singapore 529889, Singapore. [Cuevas, Carlos; Dighe, Manjiri K.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. RP Bhargava, P (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Radiol, Mail Box 358280,S-114 Radiol,1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 57 TC 1 Z9 1 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 EI 1557-8275 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 2012 VL 50 IS 2 BP 245 EP + DI 10.1016/j.rcl.2012.02.006 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 941HW UT WOS:000303955300005 PM 22498441 ER PT J AU Bhargava, P Dighe, MK Lee, JH Wang, C AF Bhargava, Puneet Dighe, Manjiri K. Lee, Jean Hwa Wang, Carolyn TI Multimodality Imaging of Ureteric Disease SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Ureter; Imaging; Transitional cell carcinoma; Calculi; Urography ID TRANSITIONAL-CELL CARCINOMA; UNENHANCED HELICAL CT; UPPER URINARY-TRACT; URETEROPELVIC JUNCTION OBSTRUCTION; MAGNETIC-RESONANCE UROGRAPHY; SHOT INTRAVENOUS PYELOGRAM; UNSTABLE TRAUMA PATIENTS; RETROPERITONEAL FIBROSIS; VOIDING CYSTOURETHROGRAPHY; COMPUTED-TOMOGRAPHY AB The proximal ureter (upper) extends from the ureteropelvic junction to where the ureter crosses the sacroiliac joint, the middle ureter courses over the bony pelvis and iliac vessels, and the distal or pelvic (lower) ureter extends from the iliac vessels to the bladder. Benign and malignant lesions can affect the ureter and these may be caused by contiguous involvement from the kidney or bladder. The ureter can be imaged by computed tomography; magnetic resonance imaging; direct pyelography, both antegrade and retrograde; nuclear medicine diuretic scan; and voiding cystourethrography. This article discusses benign, malignant, neoplastic, nonneoplastic processes involving the ureter. C1 [Dighe, Manjiri K.; Lee, Jean Hwa; Wang, Carolyn] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA 98108 USA. RP Dighe, MK (reprint author), Univ Washington, Med Ctr, Dept Radiol, Box 357115,1959 NE Pacific St, Seattle, WA 98195 USA. EM dighe@u.washington.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 117 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 2012 VL 50 IS 2 BP 271 EP + DI 10.1016/j.rcl.2012.02.008 PG 30 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 941HW UT WOS:000303955300007 PM 22498443 ER PT J AU Mirochnik, B Bhargava, P Dighe, MK Kanth, N AF Mirochnik, Brandon Bhargava, Puneet Dighe, Manjiri K. Kanth, Nalini TI Ultrasound Evaluation of Scrotal Pathology SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Ultrasound; Testis; Scrotum imaging; Scrotal imaging; Torsion; Orchitis ID COLOR DOPPLER SONOGRAPHY; TESTICULAR EPIDERMOID CYSTS; RETE TESTIS; TUNICA ALBUGINEA; TUBULAR ECTASIA; GRAY-SCALE; DIAGNOSIS; TRAUMA; LYMPHOMA; APPEARANCE AB Palpable scrotal mass, acute scrotal pain, and enlarged scrotum are common scenarios in clinical practice. The imaging modality of choice to evaluate scrotal pathology is ultrasound (US). US is key in determining if a palpable abnormality is extratesticular or intratesticular and cystic or solid. US findings help narrow the differential to benign or malignant causes. Extratesticular lesions are more common and usually benign. Rarely, extratesticular solid lesions are malignant but US features are nonspecific. Accurately diagnosing rare benign intratesticular lesions is vital to avoid unnecessary orchiectomy. This article reviews extratesticular and intratesticular lesions presenting as a palpable mass and other conditions commonly seen. C1 [Bhargava, Puneet] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA 98108 USA. [Mirochnik, Brandon; Kanth, Nalini] Nassau Univ, Med Ctr, Dept Radiol, E Meadow, NY 11554 USA. [Dighe, Manjiri K.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. RP Bhargava, P (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Radiol, Mail Box 358280,S-114 Radiol,1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 49 TC 15 Z9 16 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 2012 VL 50 IS 2 BP 317 EP + DI 10.1016/j.rcl.2012.02.005 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 941HW UT WOS:000303955300009 PM 22498445 ER PT J AU Khor, TS Fujita, H Nagata, K Shimizu, M Lauwers, GY AF Khor, Tze S. Fujita, Hiroshi Nagata, Koji Shimizu, Michio Lauwers, Gregory Y. TI Biopsy interpretation of colonic biopsies when inflammatory bowel disease is excluded SO JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Non-idiopathic inflammatory bowel disease; Biopsy interpretation; Inflammatory bowel disease; Differential diagnosis ID SOLITARY RECTAL ULCER; FOCAL ACTIVE COLITIS; MUCOSAL MAST-CELLS; OF-THE-LITERATURE; PNEUMATOSIS CYSTOIDES INTESTINALIS; SUBEPITHELIAL COLLAGEN TABLE; SELF-LIMITED COLITIS; MICROSCOPIC COLITIS; LYMPHOCYTIC COLITIS; ISCHEMIC COLITIS AB The interpretation of colonic biopsies related to inflammatory conditions can be challenging because the colorectal mucosa has a limited repertoire of morphologic responses to various injurious agents. Only few processes have specific diagnostic features, and many of the various histological patterns reflect severity and duration of the disease. Importantly the correlation with endoscopic and clinical information is often cardinal to arrive at a specific diagnosis in many cases. C1 [Khor, Tze S.; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. [Khor, Tze S.] Queen Elizabeth II Med Ctr, PathW Lab Med, Nedlands, WA 6009, Australia. [Fujita, Hiroshi] Kagoshima Univ, Grad Sch Med & Dent Sci, Kagoshima Univ Hosp, Dept Gastroenterol, Kagoshima 890, Japan. [Nagata, Koji; Shimizu, Michio] Saitama Med Univ, Int Med Ctr, Dept Pathol, Saitama, Japan. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM tzesk@member.rcpa.edu.au; GLAUWERS@partners.org NR 195 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 1-11-11 KUDAN-KITA, CHIYODA-KU, TOKYO, 102-0073, JAPAN SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PD MAR PY 2012 VL 47 IS 3 BP 226 EP 248 DI 10.1007/s00535-012-0539-6 PG 23 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 934PF UT WOS:000303455700002 PM 22322659 ER PT J AU Calkins, H Kuck, KH Cappato, R Brugada, J Camm, AJ Chen, SA Crijns, HJG Damiano, RJ Davies, DW DiMarco, J Edgerton, J Ellenbogen, K Ezekowitz, MD Haines, DE Haissaguerre, M Hindricks, G Iesaka, Y Jackman, W Jalife, J Jais, P Kalman, J Keane, D Kim, YH Kirchhof, P Klein, G Kottkamp, H Kumagai, K Lindsay, BD Mansour, M Marchlinski, FE McCarthy, PM Mont, JL Morady, F Nademanee, K Nakagawa, H Natale, A Nattel, S Packer, DL Pappone, C Prystowsky, E Raviele, A Reddy, V Ruskin, JN Shemin, RJ Tsao, HM Wilber, D AF Calkins, Hugh Kuck, Karl Heinz Cappato, Riccardo Brugada, Josep Camm, A. John Chen, Shih-Ann Crijns, Harry J. G. Damiano, Ralph J., Jr. Davies, D. Wyn DiMarco, John Edgerton, James Ellenbogen, Kenneth Ezekowitz, Michael D. Haines, David E. Haissaguerre, Michel Hindricks, Gerhard Iesaka, Yoshito Jackman, Warren Jalife, Jose Jais, Pierre Kalman, Jonathan Keane, David Kim, Young-Hoon Kirchhof, Paulus Klein, George Kottkamp, Hans Kumagai, Koichiro Lindsay, Bruce D. Mansour, Moussa Marchlinski, Francis E. McCarthy, Patrick M. Mont, J. Lluis Morady, Fred Nademanee, Koonlawee Nakagawa, Hiroshi Natale, Andrea Nattel, Stanley Packer, Douglas L. Pappone, Carlo Prystowsky, Eric Raviele, Antonio Reddy, Vivek Ruskin, Jeremy N. Shemin, Richard J. Tsao, Hsuan-Ming Wilber, David TI 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Article DE Atrial fibrillation; Catheter ablation; Surgical ablation ID PULMONARY-VEIN ISOLATION; QUALITY-OF-LIFE; CIRCULAR MAPPING CATHETER; INTENSITY FOCUSED ULTRASOUND; OBSTRUCTIVE SLEEP-APNEA; MITRAL-VALVE SURGERY; PHRENIC-NERVE INJURY; BIPOLAR RADIOFREQUENCY ABLATION; MAGNETIC-RESONANCE ANGIOGRAPHY; ANTIARRHYTHMIC-DRUG THERAPY AB This is a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation, developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch the European Society of Cardiology and the European Cardiac Arrhythmia Society (ECAS), and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). This is endorsed by the governing bodies of the ACC Foundation, the AHA, the ECAS, the EHRA, the STS, the APHRS, and the HRS. C1 [Cappato, Riccardo] IRCCS Policlin San Donato, Arrhythmia & EP Ctr, Milan, Italy. [Calkins, Hugh] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Kuck, Karl Heinz] Allgemeines Krankenhaus St Georg, Hamburg, Germany. [Chen, Shih-Ann] Taipei Vet Gen Hosp, Taipei, Taiwan. [Prystowsky, Eric] Care Grp LLC, Indianapolis, IN USA. [Natale, Andrea] St Davids Med Ctr, Texas Cardiac Arrhythmia Inst, Austin, TX USA. [Haines, David E.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Marchlinski, Francis E.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Davies, D. Wyn] Imperial Coll Healthcare NHS Trust, St Marys Hosp, London, England. [Lindsay, Bruce D.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Damiano, Ralph J., Jr.] Washington Univ, Sch Med, St Louis, MO USA. [Packer, Douglas L.] Mayo Fdn, Rochester, MN USA. [Brugada, Josep] Univ Barcelona, Hosp Clin, Barcelona, Spain. [Camm, A. John] St Georges Univ London, London, England. [Crijns, Harry J. G.] Univ Hosp Maastricht, Maastricht, Netherlands. [DiMarco, John] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Edgerton, James] Heart Hosp Baylor Plano & Cardiopulmonary Res Sci, Plano, TX USA. [Ellenbogen, Kenneth] Virginia Commonwealth Univ, Richmond, VA USA. [Ezekowitz, Michael D.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Haissaguerre, Michel] Univ Bordeaux, Hop Cardiol, Bordeaux, France. [Hindricks, Gerhard; Jais, Pierre] Univ Leipzig, Leipzig, Germany. [Iesaka, Yoshito] Tsuchiura Kyodo Gen Hosp, Tsuchiura, Ibaraki, Japan. [Jackman, Warren; Nakagawa, Hiroshi] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Jalife, Jose] Univ Michigan, Ann Arbor, MI 48109 USA. [Kalman, Jonathan] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Keane, David] St Vincents Univ Hosp, Dublin 4, Ireland. [Kim, Young-Hoon] Korea Univ, Med Ctr, Seoul, South Korea. [Kirchhof, Paulus] Univ Birmingham, Ctr Cardiovasc Sci, Birmingham, W Midlands, England. [Kirchhof, Paulus] Univ Munster, Dept Cardiol, Munster, Germany. [Klein, George] Univ Western Ontario, Univ Hosp, London, ON N6A 5A5, Canada. [Kottkamp, Hans] Clin Hirslanden, Zurich, Switzerland. [Kumagai, Koichiro] Fukuoka Sanno Hosp, Fukuoka, Japan. [Mansour, Moussa; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McCarthy, Patrick M.] NW Mem Hosp, Chicago, IL 60611 USA. [Mont, J. Lluis] Univ Barcelona, FESC Hosp Clin, Barcelona, Spain. [Morady, Fred] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Nademanee, Koonlawee] Pacific Rim EP Res Inst Ctr, Inglewood, CA USA. [Nattel, Stanley] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Pappone, Carlo] Maria Cecilia Hosp, Cotignola, Italy. [Raviele, Antonio] Umberto I Hosp, Venice, Italy. [Reddy, Vivek] Mt Sinai Sch Med, New York, NY USA. [Shemin, Richard J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Tsao, Hsuan-Ming] Natl Yang Ming Univ Hosp, Taipei, Taiwan. [Wilber, David] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. RP Cappato, R (reprint author), IRCCS Policlin San Donato, Arrhythmia & EP Ctr, Milan, Italy. EM segreteriaelettrofisiologia.ipsd@grupposandonato.it RI Pappone, Carlo/J-9853-2016; Jalife, Jose/L-4833-2015; OI Pappone, Carlo/0000-0002-0901-6135; Kirchhof, Paulus/0000-0002-1881-0197; Jalife, Jose/0000-0003-0080-3500; BRUGADA, JOSEP/0000-0002-5662-8302 FU St. Jude Medical; Biotronik; Sorin; Boston Scientific; Medtronic; Sanofi Aventis; Daiichi Sankyo; BMS; Pfizer; Servier; Johnson Johnsonm; Biosense Webster; Sorin Group; Bard; Merck; Boehringer Ingelheim; Atricure; Toray Medical; 3M Medica/MEDA Pharma; Cardovascular Therapeutics; OMRON; BMBF; Fondation Leducq; German Research Foundation; DFG; European Union; CryoCath Technologies, Inc.; Stereotaxis; Cordis Webster - Johnson Johnson; Edwards Lifesciences; Rhythmia; MC10; Voyage Medical; Rhythmia Medical; Endosense SA; AstraZeneca; NIH; Thermedical; EpiEP; Minnesota Partnership for Biotechnology and Medical Genomic / University of Minnesota; Endosense; CardioFocus; Atritech; Phillips; SentreHeart FX Research Grant St. Jude Medical (b), Biotronik (b), Sorin (b), Boston Scientific, (b), Medtronic (b), Medtronic (d), Boston Scientific (d), St. Jude Medical (d), Sanofi Aventis (e), Daiichi Sankyo (f), BMS (e), Pfizer (e), Servier (e), Johnson & Johnsonm(e), Boston Scientific (c), Biosense Webster (c), Sorin Group (c), Bard (c), St. Jude Medical (c), St Jude Medical (e), Merck (f), Sanofi Aventis (e), Boehringer Ingelheim (f), Boston Scientific (f), None Atricure (c), Medtronic (e), None Atricure (c), Medtronic (d), Boston Scientific (d), St. Jude Medical (b), Biosense Webster (d), None St. Jude Medical (b), Medtronic (b), Toray Medical (b), None Biosense Webster (c), Biotronik (d), St. Jude Medical (f), None None None None Medtronic (e), None St. Jude Medical (d), 3M Medica/MEDA Pharma (d), Cardovascular Therapeutics (d), Medtronic (d), OMRON (d), Sanofi aventis (d), St. Jude Medical (d), BMBF (d), Fondation Leducq (d), German Research Foundation (d), DFG (d), European Union (d), None None Biosense Webster (b), CryoCath Technologies, Inc. (b), Stereotaxis (b), Medtronic (b), St. Jude Medical (b), Cordis Webster - Johnson & Johnson (b), Edwards Lifesciences (b), None None Biosense Webster (d), St Jude Medical (d), Rhythmia (d), MC10 (c), Voyage Medical (c) Biosense Webster (b), St. Jude Medical (b), None St. Jude Medical (d), Boston Scientific (d), Sanofi Aventis (d), Biosense Webster (d), Medtronic (d), None Biosense Webster (a), Biosense Webster (e), St. Jude Medical (d), Stereotaxis (d), Rhythmia Medical (d), Endosense SA (d), None AstraZeneca (f), NIH (f), Medtronic (f), Thermedical (d), EpiEP (c), St. Jude Medical (f), Minnesota Partnership for Biotechnology and Medical Genomic / University of Minnesota (f), Biosense Webster (f), Biotronik (e), None None St. Jude Medical (b), Biosense Webster (b), Endosense (b), Medtronic (b), CardioFocus (b), Atritech (b), Phillips (b), Voyage Medical (b) SentreHeart (b), None None None None NR 756 TC 106 Z9 111 U1 0 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD MAR PY 2012 VL 33 IS 2 BP 171 EP 257 DI 10.1007/s10840-012-9672-7 PG 87 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 935SL UT WOS:000303540600006 PM 22382715 ER PT J AU Vakharia, KT Henstrom, D Lindsay, R Cunnane, MB Cheney, M Hadlock, T AF Vakharia, Kalpesh T. Henstrom, Douglas Lindsay, Robin Cunnane, Mary Beth Cheney, Mack Hadlock, Tessa TI Color Doppler Ultrasound: Effective Monitoring of the Buried Free Flap in Facial Reanimation SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE facial paralysis; gracilis; ultrasound; Doppler; buried free flap ID FREE TISSUE TRANSFER; HEAD AB Objective. The gracilis muscle free flap has become a reliable means for smile reanimation for patients with facial paralysis. Because it is a buried flap, it presents a postoperative monitoring challenge. We sought to evaluate our experience with color Doppler ultrasound in the monitoring of gracilis free flap viability in the immediate postoperative setting. Study Design. Case series with planned data collection. Setting. Tertiary medical center. Methods. Patients with facial paralysis treated with gracilis muscle free flap for smile reanimation performed between March 2009 and November 2010 were evaluated by color Doppler ultrasound and included in the study. Our experience with the use of the color Doppler ultrasound to monitor the gracilis muscle flap is presented. Results. Forty-six patients were identified. In all cases, color Doppler ultrasound was used postoperatively to assess flow through the vascular pedicle. Outcomes included an early flap survival rate of 100%, with no instances of equivocal or absent flow on either the arterial or venous side. Color Doppler ultrasound provided important objective information regarding muscle perfusion postoperatively in several instances of equivocal postoperative perfusion of the flap. Conclusion. Color Doppler ultrasound is a safe, noninvasive method that can be performed serially to evaluate a buried free flap. We have had success in verifying normal arterial and venous flow through the pedicle using this method of monitoring of the gracilis muscle free flap during facial reanimation, and in 3 instances, it eliminated the need for wound exploration to verify appropriate muscle perfusion. C1 [Vakharia, Kalpesh T.; Cunnane, Mary Beth; Cheney, Mack; Hadlock, Tessa] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Vakharia, Kalpesh T.; Cunnane, Mary Beth; Cheney, Mack; Hadlock, Tessa] Harvard Univ, Sch Med, Boston, MA USA. [Henstrom, Douglas] Univ Iowa, Dept Otolaryngol, Iowa City, IA USA. [Lindsay, Robin] Natl Naval Med Ctr, Dept Otolaryngol Head & Neck Surg, Bethesda, MD USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM tessa_hadlock@meei.harvard.edu NR 11 TC 12 Z9 12 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 2012 VL 146 IS 3 BP 372 EP 376 DI 10.1177/0194599811427377 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 935TX UT WOS:000303545100006 PM 22261491 ER PT J AU Lin, HW Bhattacharyya, N AF Lin, Harrison W. Bhattacharyya, Neil TI Contemporary Assessment of Medical Morbidity and Mortality in Head and Neck Surgery SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT AAO-HNSF Annual Meeting and OTO EXPO CY SEP 10-14, 2011 CL San Francisco, CA SP AAO, HNSF DE head and neck cancer; morbidity; mortality; complications ID QUALITY-OF-LIFE; ELDERLY-PATIENTS; CANCER; COMPLICATIONS; COMORBIDITY; STAY AB Objective. To update the incidence of medical morbidity and mortality in head and neck surgery and factors that influence length of stay (LOS). Study Design. Cross-sectional analysis of a national database. Setting. Academic medical center. Methods. A specific database for head and neck surgical procedures was extracted from the National Hospital Data Survey for 2005 through 2007. Records of inpatient admissions for patients undergoing head and neck surgery as the primary procedure were examined to establish the frequency of medical complications, mortality, and LOS. The association of these medical complications with mortality and LOS was determined. Results. A total of 330,629 head and neck procedures were analyzed. The overall medical morbidity and mortality rates were 5.0% +/- 0.7% and 0.4% +/- 0.2%, respectively. The most common medical complication was hospital-acquired pneumonia (3.3% +/- 0.6%), whereas acute renal failure, stroke, acute myocardial infarction, pulmonary embolism, and deep venous thrombosis were substantially less frequent (combined incidence, 2.1%). The mean LOS for patients without a major complication was 3.3 +/- 0.2 days vs 14.0 +/- 1.9 days for those with a major complication (P < .001). Conclusions. Medical morbidity and mortality in patients undergoing head and neck surgical procedures continue to be exceedingly low. Although medical complications are associated with a longer LOS, the influence of medical complications on mortality has declined. Enhancements in perioperative medical management of head and neck surgical patients are likely responsible for these improved results. C1 [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. RP Lin, HW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM harrison_lin@meei.harvard.edu NR 17 TC 5 Z9 5 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 2012 VL 146 IS 3 BP 385 EP 389 DI 10.1177/0194599811428557 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 935TX UT WOS:000303545100009 PM 22075078 ER PT J AU Wiechers, IR Viron, M Stoklosa, J Freudenreich, O Henderson, DC Weiss, A AF Wiechers, Ilse R. Viron, Mark Stoklosa, Joseph Freudenreich, Oliver Henderson, David C. Weiss, Anthony TI Impact of a Metabolic Screening Bundle on Rates of Screening for Metabolic Syndrome in a Psychiatry Resident Outpatient Clinic SO ACADEMIC PSYCHIATRY LA English DT Article ID ANTIPSYCHOTIC MEDICATIONS; SCHIZOPHRENIA AB Objective: Although it is widely acknowledged that second-generation antipsychotics are associated with cardiometabolic side effects, rates of metabolic screening have remained low. The authors created a quality-improvement (QI) intervention in an academic medical center outpatient psychiatry resident clinic with the aim of improving rates of screening for metabolic syndrome in patients being prescribed antipsychotic medications. Methods: The core components of the QI intervention included resident education and creation of a metabolic screening bundle for the electronic medical record. Quarterly audits of individual patient electronic medical records assessed whether a patient was currently prescribed antipsychotics and whether metabolic-syndrome screening had been documented at any time in the preceding 12 months. Results: In each audit period, from 131 to 156 patients (30%-36% of total clinic sample) were prescribed antipsychotic medication. After the intervention, rates of documentation of the components of the metabolic screening bundle increased between 3.5- and 10-fold (final rates: 39% for blood pressure, 44% for BMI, and 55% for glucose and lipid panel). Rates of documenting the full bundle increased nearly 30-fold (final rate: 31%). Conclusion: Provider-education combined with introduction of a documentation bundle in the electronic medical record increased rates of documented metabolic screening in patients being prescribed antipsychotic medications by psychiatry residents. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stoklosa, Joseph] McLean Hosp, Belmont, MA USA. RP Wiechers, IR (reprint author), Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. EM ilse.wiechers@yale.edu NR 10 TC 3 Z9 3 U1 2 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD MAR-APR PY 2012 VL 36 IS 2 BP 118 EP 121 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 932GL UT WOS:000303278300009 PM 22532201 ER PT J AU Blumenthal, KG Patil, SU Long, ADA AF Blumenthal, Kimberly G. Patil, Sarita U. Long, Aidan A. TI The importance of vancomycin in drug rash with eosinophilia and systemic symptoms (dress) syndrome SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID INDUCED HYPERSENSITIVITY SYNDROME; HERPESVIRUS 6 INFECTION; REACTIVATION; ASSOCIATION; HUMAN-HERPESVIRUS-6; TEICOPLANIN; USAGE AB Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome characterized by fever, rash, eosinophilia, atypical lymphocytes, and multiorgan involvement has a significant mortality. Inpatient vancomycin use is increasing and appears to be emerging as an important etiology of DRESS syndrome. This study highlights the importance of vancomycin as a cause of DRESS syndrome. We reviewed all cases of DRESS syndrome among inpatients consulted by the Allergy & Immunology service at Massachusetts General Hospital (MGH) from July 2009 through December 2010. We also reviewed the use of inpatient parenteral vancomycin over the past 4 years at MGH. Six patients fulfilled clinical criteria for DRESS syndrome, including rash, fever, eosinophilia, and hepatitis, with five (83%) having vancomycin as the attributable cause. Onset of symptoms varied from 12 days to 4 weeks after start of vancomycin treatment. Systemic findings included atypical lymphocytes, lymphadenopathy, nephritis, hypotension, tachycardia, and pharyngitis. Treatment with corticosteroids was required in three cases. Recurrence of peripheral eosinophilia was a marker of disease relapse. In three of the five patients (60%), elevated human herpesvirus 6 (HHV6) IgG titers correlated with greater systemic involvement and prolonged time to resolution. MGH pharmacy records indicate a progressive increase in the number of patients treated with parenteral vancomycin over the last 4 years. Causative agents for DRESS syndrome in an inpatient setting is likely different from that seen in the general population. With increasing use of vancomycin, we are likely to see more cases of DRESS syndrome caused by vancomycin. Recognition of vancomycin as a common cause of inpatient DRESS syndrome is important. C1 [Blumenthal, Kimberly G.; Patil, Sarita U.; Long, Aidan A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Patil, Sarita U.; Long, Aidan A.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Blumenthal, KG (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St,GRB 740, Boston, MA 02114 USA. EM kblumenthal1@partners.org NR 34 TC 14 Z9 14 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAR-APR PY 2012 VL 33 IS 2 BP 165 EP 171 DI 10.2500/aap.2012.33.3498 PG 7 WC Allergy SC Allergy GA 932FJ UT WOS:000303275500008 PM 22525393 ER PT J AU Soler, ZM Mace, JC Litvack, JR Smith, TL AF Soler, Zachary M. Mace, Jess C. Litvack, Jamie R. Smith, Timothy L. TI Chronic rhinosinusitis, race, and ethnicity SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID ENDOSCOPIC SINUS SURGERY; ALLERGIC FUNGAL RHINOSINUSITIS; QUALITY-OF-LIFE; SOCIOECONOMIC-FACTORS; SURGICAL OUTCOMES; DISEASE BURDEN; BONE EROSION; HEALTH; PERSPECTIVE; DIAGNOSIS AB Background: Little is known regarding the epidemiology of chronic rhinosinusitis (CRS) in racial and ethnic minorities in the United States. This study was designed to comprehensively evaluate the current prevalence of CRS across various treatment settings to identify possible disparities in health care access and use between racial and ethnic populations. Methods: The National Health Interview Survey (NHIS), National Ambulatory Medical Care Survey (NAMCS), and National Hospital Ambulatory Medical Care Survey (NHAMCS) database registries were extracted to identify the national prevalence of CRS in race/ethnic populations and resource use in ambulatory care settings. Systematic literature review identified studies reporting treatment outcomes in minority patients electing endoscopic sinus surgery (ESS). Data were supplemented using a multi-institutional cohort of patients undergoing surgical treatment. Results: National survey data suggest CRS is a significant health condition for all major race/ethnic groups in the United States, accounting for a sizable portion of office, emergency, and outpatient visits. Differences in insurance status, work absenteeism, and resource use were found between race/ethnic groups. Despite its prevalence, few published studies include information regarding minority patients with CRS. Most (90%) cohort studies did not provide details of race/ethnicity for ESS outcomes. Prospective cohort analysis indicated that minority surgical patients accounted for only 18%, when compared with national census estimates (35%). Conclusion: CRS is an important health condition for all major race/ethnic groups in the United States. Significant differences may exist across racial and ethnic categories with regard to CRS health status and health care use. Given current demographic shifts in the United States, specific attention should be given to understanding CRS within the context of racial and ethnic populations. Public clinical trial registration (www.clinicaltrials.gov) I. D. No. NCT00799097. (Am J Rhinol Allergy 26, 110-116, 2012; doi: 10.2500/ajra.2012.26.3741) C1 [Mace, Jess C.; Smith, Timothy L.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Div Rhinol & Sinus Surg, Oregon Sinus Ctr, Portland, OR 97239 USA. [Soler, Zachary M.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Litvack, Jamie R.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Smith, TL (reprint author), Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Div Rhinol & Sinus Surg, Oregon Sinus Ctr, 3181 SW Sam Jackson Pk Rd PV-01, Portland, OR 97239 USA. EM smithtim@ohsu.edu FU National Institute on Deafness and Other Communication Disorders, one of the National Institutes of Health [DC005805]; National Institute on Deafness and Other Communication Disorders, one of the National Institutes of Health, Bethesda, MD [DC005805] FX Funded by a grant from the National Institute on Deafness and Other Communication Disorders, one of the National Institutes of Health (DC005805; PI: T. Smith); TL Smith is a consultant for Intersect ENT, Inc., Palo Alto, CA, which provided no financial support for this investigation. TL Smith and JC Mace also received grant funding (DC005805) from the National Institute on Deafness and Other Communication Disorders, one of the National Institutes of Health, Bethesda, MD, for data collection associated with this investigation. The remaining author had no conflicts of interest to declare pertaining to this article NR 32 TC 29 Z9 29 U1 0 U2 4 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD MAR-APR PY 2012 VL 26 IS 2 BP 110 EP 116 DI 10.2500/ajra.2012.26.3741 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 930OI UT WOS:000303148400012 PM 22487286 ER PT J AU Trippa, L Rosner, GL Muller, P AF Trippa, Lorenzo Rosner, Gary L. Mueller, Peter TI Bayesian Enrichment Strategies for Randomized Discontinuation Trials SO BIOMETRICS LA English DT Article DE Clinical trials; Enrichment designs; Randomized discontinuation design; Tumor growth models ID RENAL-CELL CARCINOMA; TUMOR-GROWTH; STOCHASTIC-MODEL; DESIGN; AGENTS; PARAMETER; POWER AB We propose optimal choice of the design parameters for random discontinuation designs (RDD) using a Bayesian decision-theoretic approach. We consider applications of RDDs to oncology phase II studies evaluating activity of cytostatic agents. The design consists of two stages. The preliminary open-label stage treats all patients with the new agent and identifies a possibly sensitive subpopulation. The subsequent second stage randomizes, treats, follows, and compares outcomes among patients in the identified subgroup, with randomization to either the new or a control treatment. Several tuning parameters characterize the design: the number of patients in the trial, the duration of the preliminary stage, and the duration of follow-up after randomization. We define a probability model for tumor growth, specify a suitable utility function, and develop a computational procedure for selecting the optimal tuning parameters. C1 [Trippa, Lorenzo] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Trippa, Lorenzo] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Rosner, Gary L.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Biostat & Bioinformat, Baltimore, MD 21205 USA. [Mueller, Peter] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. RP Trippa, L (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM lorenzo.trippa@jimmi.harvard.com; grosner@jhmi.edu; pmueller@mdanderson.org FU U.S. National Cancer Institute [CA075981] FX This research was supported in part by grant CA075981 from the U.S. National Cancer Institute. We thank the CALGB and Ms Susan Sutherland for the historical tumor growth data. NR 29 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2012 VL 68 IS 1 BP 203 EP 211 DI 10.1111/j.1541-0420.2011.01623.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 914BT UT WOS:000301924400023 PM 21714780 ER PT J AU Gray, SW Landrum, MB Lamont, EB McNeil, BJ Jaklitsch, MT Keating, NL AF Gray, Stacy W. Landrum, Mary Beth Lamont, Elizabeth B. McNeil, Barbara J. Jaklitsch, Michael T. Keating, Nancy L. TI Improved Outcomes Associated With Higher Surgery Rates for Older Patients With Early Stage Nonsmall Cell Lung Cancer SO CANCER LA English DT Article DE nonsmall cell lung cancer; surgery; survival; geriatric oncology; comorbidity ID CLINICAL-PRACTICE GUIDELINES; ACUTE MYOCARDIAL-INFARCTION; ELDERLY-PATIENTS; REGIONAL-VARIATIONS; CLAIMS DATA; RESECTION; MORTALITY; SURVIVAL; MANAGEMENT; DIAGNOSIS AB BACKGROUND: Although surgery offers the greatest chance of a cure for patients with early stage nonsmall cell lung cancer (NSCLC), older and sicker patients often fail to undergo resection. The benefits of surgery in older patients and patients with multiple comorbidities are uncertain. METHODS: The authors identified a national cohort of 17,638 Medicare beneficiaries aged >= 66 years living in Surveillance, Epidemiology, and End Results (SEER) areas who were diagnosed with stage I or II NSCLC during 2001 to 2005. Areas with high and low rates of curative surgery for early stage lung cancer were compared to estimate the effectiveness of surgery in older and sicker patients. Logistic regression models were used to assess mortality according to the quintile of area-level surgery rates, adjusting for potential confounders. RESULTS: Less than 63% of patients underwent surgery in low-surgery areas, whereas >79% underwent surgery in high-surgery areas. High-surgery areas operated on more patients of advanced age and patients with chronic obstructive pulmonary disease than low-surgery areas. The adjusted all-cause 1 year mortality was 18% in high-surgery areas versus 22.8% in low-surgery areas (adjusted odds ratio [OR], 0.89; 95% confidence interval [CI], 0.86-0.93) for each 10% increase in the surgery rate). The 1-year lung-cancer-specific mortality similarly was lower in high-surgery areas (12%) versus low-surgery areas (16.9%; adjusted OR, 0.86; 95% CI, 0.82-0.91) for each 10% increase in the surgery rate. CONCLUSIONS: Higher rates of surgery for stage I/II NSCLC were associated with improved survival, even when older patients and sicker patients underwent resection. The authors concluded that more work is needed to identify and reduce barriers to surgery for early stage NSCLC. Cancer 2012; 118: 1404-11. (C) 2011 American Cancer Society. C1 [Landrum, Mary Beth; Lamont, Elizabeth B.; McNeil, Barbara J.; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Gray, Stacy W.; Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Gray, Stacy W.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Div Adult Oncol, Boston, MA 02114 USA. [McNeil, Barbara J.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Jaklitsch, Michael T.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU Department of Veterans Affairs; National Cancer Institute [R01CA142744] FX The work was supported by the Department of Veterans Affairs as part of a larger evaluation of oncology care and by the National Cancer Institute (R01CA142744). The funders had no role in the design or conduct of the study; in the collection, management, analysis, or interpretation of the data; or in the preparation, review, or approval of the article. NR 31 TC 14 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAR 1 PY 2012 VL 118 IS 5 BP 1404 EP 1411 DI 10.1002/cncr.26363 PG 8 WC Oncology SC Oncology GA 897QD UT WOS:000300667800028 PM 21800285 ER PT J AU Perrin, JM AF Perrin, James M. TI How Can Quality Improvement Enhance the Lives of Children with Disabilities? SO FUTURE OF CHILDREN LA English DT Article ID MEDICAL HOME MODEL; HEALTH-CARE; UNITED-STATES; DISEASE; ATTENTION; DISORDER; ASTHMA; AUTISM; YOUTH; CLASSIFICATION AB Much attention has aided measurement and improvement in the quality of health care during the past two decades, with new ways to define and measure quality, recognition that doing so can identify strategies to enhance care, and systematic efforts by both government and private insurers to apply these principles. In this article, James Perrin reviews these gains. Although children have benefited; these quality measurement efforts have focused mainly on adult health care. Now, two recent federal programs promise to expand quality measurement of child health care. Enacted in 2009, the Children's Health Insurance Program Reauthorization Act provides systematic support for efforts to develop and implement a set of child health quality measures. This federal support represents the first major public investment in improving child health care quality. The Affordable Care Act, which became law in 2010, extends those activities by focusing attention on improving care for people with chronic conditions, including new ways to organize care using teams of doctors, nurses, and others focused on improving chronic care outcomes. For children especially, this team care should also focus on prevention of chronic conditions and their consequences. Despite these significant efforts to expand quality measurement among children and youth, Perrin finds that most measures and improvement activities focus on children without chronic conditions, and few measures of chronic conditions go beyond examining what kinds of monitoring children with specific conditions receive. Only limited attention is paid to how well the children are functioning. A number of networks working with children with specific chronic health conditions (such as cancer, cystic fibrosis, and sickle cell disease) have developed effective measures of functioning for children with those conditions and active programs to improve such outcomes. These networks offer the best examples of how to improve care and outcomes for young people with disabilities. Broadening their impact to larger numbers of children with disabilities will require developing measures of functioning and quality of life and targeting interventions and efforts to improve those outcomes. C1 [Perrin, James M.] MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Perrin, James M.] Harvard Univ, Med Sch, Cambridge, MA 02138 USA. RP Perrin, JM (reprint author), MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. NR 63 TC 6 Z9 6 U1 1 U2 11 PU PRINCETON UNIV PI PRINCETON PA 277 WALLACE HALL, PRINCETON, NJ 08544 USA SN 1054-8289 J9 FUTURE CHILD JI Future Child. PD SPR PY 2012 VL 22 IS 1 BP 149 EP 168 PG 20 WC Family Studies; Health Policy & Services; Social Sciences, Interdisciplinary SC Family Studies; Health Care Sciences & Services; Social Sciences - Other Topics GA 930LA UT WOS:000303139700007 PM 22550689 ER PT J AU Barroilhet, L Garrett, L Bernstein, M Esselen, K Goldstein, D Berkowitz, R AF Barroilhet, L. Garrett, L. Bernstein, M. Esselen, K. Goldstein, D. Berkowitz, R. TI Update on subsequent pregnancy outcomes in patients with molar pregnancy and persistent gestational trophoblastic neoplasia SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Barroilhet, L.; Bernstein, M.; Esselen, K.; Goldstein, D.; Berkowitz, R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Garrett, L.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 200 BP S83 EP S84 DI 10.1016/j.ygyno.2011.12.201 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600200 ER PT J AU Boruta, D Bradford, L AF Boruta, D. Bradford, L. TI Laparoendoscopic single-site extraperitoneal paraaortic lymphadenectomy for endometrial cancer staging SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Boruta, D.; Bradford, L.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 16 BP S9 EP S9 DI 10.1016/j.ygyno.2011.12.017 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600018 ER PT J AU Bradford, L Zhang, L Groeneweg, J Borger, D Engelman, J Foster, R Growdon, W Schorge, J Rueda, B AF Bradford, L. Zhang, L. Groeneweg, J. Borger, D. Engelman, J. Foster, R. Growdon, W. Schorge, J. Rueda, B. TI Inhibition of PI3K-AKT signaling precludes endometrial cancer growth in a primary human xenograft model harboring an oncogenic PIK3CA mutation SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Bradford, L.; Zhang, L.; Groeneweg, J.; Borger, D.; Engelman, J.; Foster, R.; Growdon, W.; Schorge, J.; Rueda, B.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 312 BP S128 EP S129 DI 10.1016/j.ygyno.2011.12.313 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600310 ER PT J AU Brooks, R Darcy, K Tritchler, D Gold, D Birrer, M Rader, J Kizer, N Thaker, P Mutch, D Goodfellow, P AF Brooks, R. Darcy, K. Tritchler, D. Gold, D. Birrer, M. Rader, J. Kizer, N. Thaker, P. Mutch, D. Goodfellow, P. TI Single nucleotide polymorphisms in IL8RB, EGFR, ABL1, and SPAG9 Are associated with lymph node metastasis in endometrial cancer: A Gynecologic Oncology Group and Washington University School of Medicine study SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Brooks, R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Darcy, K.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Tritchler, D.] Univ Toronto, Toronto, ON, Canada. [Gold, D.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rader, J.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Kizer, N.; Thaker, P.; Mutch, D.; Goodfellow, P.] Washington Univ, Sch Med, St Louis, MO 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 39 BP S17 EP S17 DI 10.1016/j.ygyno.2011.12.040 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600041 ER PT J AU Campos, S Berlin, S Lundquist, C Roche, M Whalen, C Horowitz, N Penson, R AF Campos, S. Berlin, S. Lundquist, C. Roche, M. Whalen, C. Horowitz, N. Penson, R. TI A phase I study AZD2171 and Temsirolimus in advanced GYN cancers SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Campos, S.] Harvard Univ, Sch Med, Boston, MA USA. [Berlin, S.; Lundquist, C.; Whalen, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Roche, M.; Penson, R.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Horowitz, N.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 188 BP S78 EP S79 DI 10.1016/j.ygyno.2011.12.189 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600188 ER PT J AU Chan, J Java, J Monk, B Alvarez-Secord, A Kapp, D Birrer, M Aghajanian, C Bookman, M Kattan, M Burger, R AF Chan, J. Java, J. Monk, B. Alvarez-Secord, A. Kapp, D. Birrer, M. Aghajanian, C. Bookman, M. Kattan, M. Burger, R. TI A practical prediction model for determining bevacizumab response and toxicity in the treatment of advanced ovarian and peritoneal cancers - An analysis of GOG 218 SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Chan, J.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Java, J.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Monk, B.] Creighton Univ, Sch Med, Phoenix, AZ USA. [Alvarez-Secord, A.] Duke Univ, Med Ctr, Durham, NC USA. [Kapp, D.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Aghajanian, C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bookman, M.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Kattan, M.] Cleveland Clin, Cleveland, OH 44106 USA. [Burger, R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 69 BP S31 EP S31 DI 10.1016/j.ygyno.2011.12.070 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600071 ER PT J AU Diver, E O'Connor, O Garrett, L Bradford, L Boruta, D Goodman, A Del Carmen, M Schorge, J Mueller, P Growdon, W AF Diver, E. O'Connor, O. Garrett, L. Bradford, L. Boruta, D. Goodman, A. Del Carmen, M. Schorge, J. Mueller, P. Growdon, W. TI Modest benefit of total parenteral nutrition and chemotherapy after venting gastrostomy tube placement SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Diver, E.] Brigham & Womens Massachusetts Gen Hosp, Boston, MA USA. [O'Connor, O.; Garrett, L.; Bradford, L.; Boruta, D.; Goodman, A.; Del Carmen, M.; Schorge, J.; Mueller, P.; Growdon, W.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 171 BP S72 EP S72 DI 10.1016/j.ygyno.2011.12.172 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600171 ER PT J AU Goodman, A Sullivan, L Lafleur, K Penson, R Schorge, J Del Carmen, M Boruta, D Growdon, W Krasner, C Birrer, M AF Goodman, A. Sullivan, L. Lafleur, K. Penson, R. Schorge, J. Del Carmen, M. Boruta, D. Growdon, W. Krasner, C. Birrer, M. TI Impact of drug shortages on cancer care: The story of pegylated liposomal doxorubicin in ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Goodman, A.; Sullivan, L.; Lafleur, K.; Penson, R.; Schorge, J.; Del Carmen, M.; Boruta, D.; Growdon, W.; Krasner, C.; Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 158 BP S66 EP S67 DI 10.1016/j.ygyno.2011.12.159 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600158 ER PT J AU Holman, L Lu, K Hernandez, M Bast, R Bodurka, D Skates, S Gershenson, D Sun, C AF Holman, L. Lu, K. Hernandez, M. Bast, R. Bodurka, D. Skates, S. Gershenson, D. Sun, C. TI Perception of risk, cancer worry, anxiety, and acceptability of screening among low-risk women undergoing ovarian cancer screening with the risk of ovarian cancer algorithm SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Holman, L.; Lu, K.; Hernandez, M.; Bast, R.; Bodurka, D.; Gershenson, D.; Sun, C.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Skates, S.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 280 BP S116 EP S117 DI 10.1016/j.ygyno.2011.12.281 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600278 ER PT J AU Kim, S Vathipadiekal, V Kikuchi, J Mohapatra, G Cho, H Nam, E Kim, S Kim, J Kim, Y Birrer, M AF Kim, S. Vathipadiekal, V. Kikuchi, J. Mohapatra, G. Cho, H. Nam, E. Kim, S. Kim, J. Kim, Y. Birrer, M. TI Role of synaptotagmin-like 2 (SYTL2) in ovarian cancer progression SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Kim, S.; Cho, H.; Nam, E.; Kim, S.; Kim, J.; Kim, Y.] Yonsei Univ, Coll Med, Seoul, South Korea. [Vathipadiekal, V.; Kikuchi, J.; Mohapatra, G.; Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 336 BP S138 EP S138 DI 10.1016/j.ygyno.2011.12.337 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600334 ER PT J AU May, T Shoni, M Vitonis, A Quick, C Growdon, W Muto, M AF May, T. Shoni, M. Vitonis, A. Quick, C. Growdon, W. Muto, M. TI Can we safely omit paraaortic lymphadenectomy from the surgical staging of high-grade endometrioid, clear cell and papillary serous endometrial adenocarcinoma? SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [May, T.; Shoni, M.; Vitonis, A.; Muto, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Quick, C.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Growdon, W.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 399 BP S162 EP S163 DI 10.1016/j.ygyno.2011.12.400 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600395 ER PT J AU May, T Yang, J Shoni, M Liu, S He, H Gali, R Berkowitz, R Ng, S AF May, T. Yang, J. Shoni, M. Liu, S. He, H. Gali, R. Berkowitz, R. Ng, S. TI BRCA1 expression is suppressed in sporadic ovarian cancer cells by overexpression of C-terminal binding protein-2 SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [May, T.; Yang, J.; Shoni, M.; Liu, S.; Berkowitz, R.; Ng, S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [He, H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gali, R.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 348 BP S142 EP S142 DI 10.1016/j.ygyno.2011.12.349 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600346 ER PT J AU May, T Virtanen, C Crum, C Xian, W Vathipadiekal, V Birrer, M Rosen, B Murphy, K Tone, A AF May, T. Virtanen, C. Crum, C. Xian, W. Vathipadiekal, V. Birrer, M. Rosen, B. Murphy, K. Tone, A. TI Multi-center gene expression analysis of Mullerian low-grade and high-grade serous carcinoma highlights genes potentially involved in chemotherapy resistance SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [May, T.; Crum, C.; Xian, W.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Virtanen, C.] Univ Hlth Network Microarray Ctr, Toronto, ON, Canada. [Vathipadiekal, V.; Birrer, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rosen, B.; Murphy, K.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Tone, A.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 256 BP S107 EP S108 DI 10.1016/j.ygyno.2011.12.257 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600255 ER PT J AU Oduyebo, T Seidman, M Rauh-Hain, A Jessel, R Del Carmen, M Horowitz, N Muto, M AF Oduyebo, T. Seidman, M. Rauh-Hain, A. Jessel, R. Del Carmen, M. Horowitz, N. Muto, M. TI The role of re-exploration in patients with morcellated leiomyosarcoma and smooth muscle tumor of uncertain malignant potential SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Oduyebo, T.; Seidman, M.; Rauh-Hain, A.; Jessel, R.; Horowitz, N.; Muto, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Del Carmen, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 375 BP S152 EP S153 DI 10.1016/j.ygyno.2011.12.376 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600371 ER PT J AU Rauh-Hain, J Winograd, D Growdon, W Schorge, J Good-man, A Boruta, D Horowitz, N Del Carmen, M AF Rauh-Hain, J. Winograd, D. Growdon, W. Schorge, J. Good-man, A. Boruta, D. Horowitz, N. Del Carmen, M. TI Prognostic determinants in patients with uterine and ovarian clear carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Winograd, D.; Growdon, W.; Schorge, J.; Good-man, A.; Boruta, D.; Del Carmen, M.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Horowitz, N.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 220 BP S91 EP S92 DI 10.1016/j.ygyno.2011.12.221 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600220 ER PT J AU Semaan, A Oliva, E Nucci, M Morris, R Al-Wahab, Z Mert, I Hussein, Y Munkarah, A Ali-Fehmi, R AF Semaan, A. Oliva, E. Nucci, M. Morris, R. Al-Wahab, Z. Mert, I. Hussein, Y. Munkarah, A. Ali-Fehmi, R. TI Clinical and pathologic characteristics of uterine serous carcinoma without myometrial invasion: A multi institutional study SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Semaan, A.; Morris, R.; Al-Wahab, Z.; Mert, I.; Hussein, Y.; Ali-Fehmi, R.] Wayne State Univ, Detroit, MI USA. [Oliva, E.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Munkarah, A.] Henry Ford Hosp, Detroit, MI 48202 USA. [Nucci, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 410 BP S167 EP S167 DI 10.1016/j.ygyno.2011.12.411 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600406 ER PT J AU Shah, N Akileswaran, C Garrett, L Bradford, L Del Carmen, M Goodman, A Schorge, J Boruta, D Growdon, W AF Shah, N. Akileswaran, C. Garrett, L. Bradford, L. Del Carmen, M. Goodman, A. Schorge, J. Boruta, D. Growdon, W. TI The effect of a paradigm shift towards minimally invasive surgery on hospitalization costs of hysterectomy for endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Akileswaran, C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Garrett, L.; Bradford, L.; Del Carmen, M.; Goodman, A.; Schorge, J.; Boruta, D.; Growdon, W.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Shah, N.] Massachusetts Gen Hosp, 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 46 BP S19 EP S20 DI 10.1016/j.ygyno.2011.12.047 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600047 ER PT J AU Taylor, S Kelley, J Rauh-Hain, J Boisen, M Sukumvanich, P Richard, S Zorn, K Christopherson, W Krivak, T Olawaiye, A AF Taylor, S. Kelley, J. Rauh-Hain, J. Boisen, M. Sukumvanich, P. Richard, S. Zorn, K. Christopherson, W. Krivak, T. Olawaiye, A. TI An assessment of risk factors for superficial surgical site infection (SSI) and superficial wound separation (SWS) in gynecologic oncology patients SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Taylor, S.; Kelley, J.; Boisen, M.; Sukumvanich, P.; Richard, S.; Zorn, K.; Christopherson, W.; Krivak, T.; Olawaiye, A.] Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Pittsburgh, PA 15213 USA. [Rauh-Hain, J.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 180 BP S75 EP S76 DI 10.1016/j.ygyno.2011.12.181 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600180 ER PT J AU Wethington, S Cibula, D Duska, L Garrett, L Kim, C Sonoda, Y Abu-Rustum, N AF Wethington, S. Cibula, D. Duska, L. Garrett, L. Kim, C. Sonoda, Y. Abu-Rustum, N. TI An international series on abdominal trachelectomy: 101 patients and 28 pregnancies SO GYNECOLOGIC ONCOLOGY LA English DT Meeting Abstract C1 [Wethington, S.; Kim, C.; Sonoda, Y.; Abu-Rustum, N.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Duska, L.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Garrett, L.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2012 VL 125 SU 1 MA 4 BP S4 EP S4 DI 10.1016/j.ygyno.2011.12.005 PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 931NW UT WOS:000303227600006 ER PT J AU Carvunis, AR Dreze, M AF Carvunis, Anne-Ruxandra Dreze, Matija TI Virulence effectors target key proteins of interactome networks of host plant cells SO M S-MEDECINE SCIENCES LA French DT News Item ID IMMUNE-SYSTEM; ARABIDOPSIS; INFECTION; VIRUS C1 [Carvunis, Anne-Ruxandra] Dana Farber Canc Inst, CCSB, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Carvunis, AR (reprint author), Dana Farber Canc Inst, CCSB, Boston, MA 02215 USA. EM anne-ruxandra_carvunis@dfci.harvard.edu OI , /0000-0001-7002-8488; Carvunis, Anne-Ruxandra/0000-0002-6474-6413 NR 10 TC 1 Z9 1 U1 0 U2 5 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD MAR PY 2012 VL 28 IS 3 BP 237 EP 239 DI 10.1051/medsci/2012283003 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 933MF UT WOS:000303365100003 PM 22480639 ER PT J AU Stathatos, N AF Stathatos, Nikolaos TI Thyroid Physiology SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Thyroid physiology; Thyroxine; Triiodothyronine; Deiodinase; Nuclear receptors ID OF-THE-LITERATURE; HORMONE-RECEPTORS; PENDRED SYNDROME; THYROXINE; HYPOTHYROIDISM; THYROTROPIN; DISEASE; PROTEIN; IODIDE; GLAND AB The thyroid gland produces thyroid hormone, which has clinically important actions practically in every system in the human body. Detailed knowledge of the physiology of the thyroid gland is critical for the proper management of thyroid disorders. The molecular biology of thyroid function is being studied in great detail. Clinically important molecules, such as the thyroid-stimulating hormone receptor and the sodium/iodide symporter, have been identified and well characterized. Such discoveries have significantly improved our understanding of thyroid physiology. As a result, new diagnostic and therapeutic approaches for the management of thyroid disorders are now available or in development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Thyroid Unit, Boston, MA 02114 USA. RP Stathatos, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Thyroid Unit, 15 Parkman St,WACC 730S, Boston, MA 02114 USA. EM nstathatos@partners.org NR 49 TC 8 Z9 8 U1 5 U2 11 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAR PY 2012 VL 96 IS 2 BP 165 EP + DI 10.1016/j.mcna.2012.01.007 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 932HT UT WOS:000303282000002 PM 22443969 ER PT J AU Shakeri, R Kamangar, F Nasrollahzadeh, D Nouraie, M Khademi, H Etemadi, A Islami, F Marjani, H Fahimi, S Sepehr, A Rahmati, A Abnet, CC Dawsey, SM Brennan, P Boffetta, P Malekzadeh, R Majdzadeh, R AF Shakeri, Ramin Kamangar, Farin Nasrollahzadeh, Dariush Nouraie, Mehdi Khademi, Hooman Etemadi, Arash Islami, Farhad Marjani, Hajiamin Fahimi, Saman Sepehr, Alireza Rahmati, Atieh Abnet, Christian C. Dawsey, Sanford M. Brennan, Paul Boffetta, Paolo Malekzadeh, Reza Majdzadeh, Reza TI Is Opium a Real Risk Factor for Esophageal Cancer or Just a Methodological Artifact? Hospital and Neighborhood Controls in Case-Control Studies SO PLOS ONE LA English DT Article ID POPULATION-CONTROLS; GOLESTAN COHORT; NORTHERN IRAN; ALCOHOL; SELECTION; QUESTION; TOBACCO; TRACT; AREA; DIET AB Background: Control selection is a major challenge in epidemiologic case-control studies. The aim of our study was to evaluate using hospital versus neighborhood control groups in studying risk factors of esophageal squamous cell carcinoma (ESCC). Methodology/Principal Findings: We compared the results of two different case-control studies of ESCC conducted in the same region by a single research group. Case definition and enrollment were the same in the two studies, but control selection differed. In the first study, we selected two age-and sex-matched controls from inpatient subjects in hospitals, while for the second we selected two age-and sex-matched controls from each subject's neighborhood of residence. We used the test of heterogeneity to compare the results of the two studies. We found no significant differences in exposure data for tobacco-related variables such as cigarette smoking, chewing Nass (a tobacco product) and hookah (water pipe) usage, but the frequency of opium usage was significantly different between hospital and neighborhood controls. Consequently, the inference drawn for the association between ESCC and tobacco use did not differ between the studies, but it did for opium use. In the study using neighborhood controls, opium use was associated with a significantly increased risk of ESCC (adjusted OR 1.77, 95% CI 1.17-2.68), while in the study using hospital controls, this was not the case (OR 1.09, 95% CI 0.63-1.87). Comparing the prevalence of opium consumption in the two control groups and a cohort enrolled from the same geographic area suggested that the neighborhood controls were more representative of the study base population for this exposure. Conclusions/Significance: Hospital and neighborhood controls did not lead us to the same conclusion for a major hypothesized risk factor for ESCC in this population. Our results show that control group selection is critical in drawing appropriate conclusions in observational studies. C1 [Shakeri, Ramin; Kamangar, Farin; Nasrollahzadeh, Dariush; Nouraie, Mehdi; Khademi, Hooman; Etemadi, Arash; Islami, Farhad; Marjani, Hajiamin; Fahimi, Saman; Sepehr, Alireza; Rahmati, Atieh; Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran. [Shakeri, Ramin; Kamangar, Farin; Etemadi, Arash; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA. [Nasrollahzadeh, Dariush] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Nouraie, Mehdi] Howard Univ, Dept Internal Med, Washington, DC 20059 USA. [Nouraie, Mehdi] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Khademi, Hooman; Islami, Farhad; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Fahimi, Saman] Univ Cambridge, Cambridge, England. [Sepehr, Alireza] Harvard Univ, Sch Med, Dept Pathol, BIDMC, Boston, MA 02115 USA. [Rahmati, Atieh] Univ Tehran Med Sci, Firoozgar Hosp, Gastrointestinal & Liver Dis Res Ctr, Tehran, Iran. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Majdzadeh, Reza] Univ Tehran Med Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Tehran, Iran. [Majdzadeh, Reza] Univ Tehran Med Sci, Knowledge Utilizat Res Ctr, Tehran, Iran. RP Shakeri, R (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran. EM rezamajd@tums.ac.ir RI Abnet, Christian/C-4111-2015; Etemadi, Arash/C-1386-2016; OI Abnet, Christian/0000-0002-3008-7843; Etemadi, Arash/0000-0002-3458-1072; , Ramin/0000-0003-0487-3629; Malekzadeh, Reza/0000-0003-1043-3814 NR 23 TC 8 Z9 8 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 1 PY 2012 VL 7 IS 3 AR e32711 DI 10.1371/journal.pone.0032711 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 928SU UT WOS:000303005000036 PM 22396792 ER PT J AU Hobai, I Buys, E Armoundas, A Siwik, D Brouckaert, P AF Hobai, Ion Buys, Emmanuel Armoundas, Antonis Siwik, Deborah Brouckaert, Peter TI Cellular mechanisms of cardiac dysfunction in endotoxemic mice SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Meeting Abstract CT 15th World-Federation-of-Societies-of-Anaesthesiologists (WFSA) World Congress of Anaesthesiologists CY MAR 25-30, 2012 CL Buenos Aires, ARGENTINA SP World Federat Soc Anaesthesiol (WFSA) C1 [Hobai, Ion; Buys, Emmanuel; Armoundas, Antonis] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Siwik, Deborah] Boston Univ, Med Ctr, Boston, MA USA. [Brouckaert, Peter] Flanders Inst Biotechnol VIB, Ghent, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD MAR PY 2012 VL 108 SU 2 BP 146 EP 146 PG 1 WC Anesthesiology SC Anesthesiology GA 919CT UT WOS:000302299100243 ER PT J AU Bugembe, R Duan, M Dubowitz, G Costello, F Ttendo, S AF Bugembe, Richard Duan, Melissa Dubowitz, Gerald Costello, Frank Ttendo, Stephen TI A pilot project of anesthesia education by video-conferencing between Uganda and the United States SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Meeting Abstract CT 15th World-Federation-of-Societies-of-Anaesthesiologists (WFSA) World Congress of Anaesthesiologists CY MAR 25-30, 2012 CL Buenos Aires, ARGENTINA SP World Federat Soc Anaesthesiol (WFSA) C1 [Bugembe, Richard; Costello, Frank] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Duan, Melissa; Ttendo, Stephen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dubowitz, Gerald] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD MAR PY 2012 VL 108 SU 2 BP 175 EP 176 PG 2 WC Anesthesiology SC Anesthesiology GA 919CT UT WOS:000302299100291 ER PT J AU Vassallo, S AF Vassallo, Susan TI Digitizing Our Past: The Wood Library-Museum of Anesthesiology and The Ether Controversy Experience SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Meeting Abstract CT 15th World-Federation-of-Societies-of-Anaesthesiologists (WFSA) World Congress of Anaesthesiologists CY MAR 25-30, 2012 CL Buenos Aires, ARGENTINA SP World Federat Soc Anaesthesiol (WFSA) C1 [Vassallo, Susan] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Management, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD MAR PY 2012 VL 108 SU 2 BP 182 EP 183 PG 2 WC Anesthesiology SC Anesthesiology GA 919CT UT WOS:000302299100302 ER PT J AU El Ouaamari, A Kawamori, D Liew, CW Dirice, E Hu, J Katsuta, H Shadrach, J Hollister-Lock, J Wagers, A Kulkarni, R AF El Ouaamari, A. Kawamori, D. Liew, C. W. Dirice, E. Hu, J. Katsuta, H. Shadrach, J. Hollister-Lock, J. Wagers, A. Kulkarni, R. TI Systemic origins of hepatic origin regulates pancreatic beta cell mass in animals resistent to insulin SO DIABETES & METABOLISM LA French DT Meeting Abstract C1 [El Ouaamari, A.; Kawamori, D.; Liew, C. W.; Dirice, E.; Hu, J.; Katsuta, H.; Shadrach, J.; Hollister-Lock, J.; Wagers, A.; Kulkarni, R.] Joslin Diabet Ctr, Boston, MA 02215 USA. RI Dirice, Ercument/B-2825-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 1262-3636 J9 DIABETES METAB JI Diabetes Metab. PD MAR PY 2012 VL 38 SI 2 BP A8 EP A8 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 926GN UT WOS:000302819400033 ER PT J AU Ruggiero, KJ Gros, K McCauley, JL Resnick, HS Morgan, M Kilpatrick, DG Muzzy, W Acierno, R AF Ruggiero, Kenneth J. Gros, Kirstin McCauley, Jenna L. Resnick, Heidi S. Morgan, Mark Kilpatrick, Dean G. Muzzy, Wendy Acierno, Ron TI Mental Health Outcomes Among Adults in Galveston and Chambers Counties After Hurricane Ike SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Article DE disaster mental health; Hurricane Ike; resilience; recovery ID POSTTRAUMATIC-STRESS-DISORDER; PREVALENCE; DISASTER; COMORBIDITY; ILLNESS; KATRINA; TEXAS; PTSD AB Objective: To examine the mental health effects of Hurricane Ike, the third costliest hurricane in US history, which devastated the upper Texas coast in September 2008. Method: Structured telephone interviews assessing immediate effects of Hurricane Ike (damage, loss, displacement) and mental health diagnoses were administered via random digit-dial methods to a household probability sample of 255 Hurricane Ike-affected adults in Galveston and Chambers counties. Results: Three-fourths of respondents evacuated the area because of Hurricane Ike and nearly 40% were displaced for at least one week. Postdisaster mental health prevalence estimates were 5.9% for posttraumatic stress disorder, 4.5% for major depressive episode, and 9.3% for generalized anxiety disorder. Bivariate analyses suggested that peritraumatic indicators of hurricane exposure severity-such as lack of adequate clean clothing, electricity, food, money, transportation, or water for at least one week-were most consistently associated with mental health problems. Conclusions: The significant contribution of factors such as loss of housing, financial means, clothing, food, and water to the development and/or maintenance of negative mental health consequences highlights the importance of systemic postdisaster intervention resources targeted to meet basic needs in the postdisaster period. (Disaster Med Public Health Preparedness. 2012;6:26-32) C1 [Ruggiero, Kenneth J.; Gros, Kirstin; McCauley, Jenna L.; Resnick, Heidi S.; Kilpatrick, Dean G.; Muzzy, Wendy; Acierno, Ron] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.; Acierno, Ron] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Morgan, Mark] Abt SRBI, New York, NY USA. RP Ruggiero, KJ (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,MSC 861, Charleston, SC 29425 USA. EM ruggierk@musc.edu FU National Institute of Mental Health (NIMH) [R34 MH77149] FX This study was supported by National Institute of Mental Health (NIMH) grant R34 MH77149 (Dr Ruggiero). NR 29 TC 11 Z9 11 U1 6 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD MAR PY 2012 VL 6 IS 1 BP 26 EP 32 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 925SO UT WOS:000302781800006 PM 22490934 ER PT J AU Valassi, E Brick, DJ Johnson, JC Biller, BMK Klibanski, A Miller, KK AF Valassi, Elena Brick, Danielle J. Johnson, Jessica C. Biller, Beverly M. K. Klibanski, Anne Miller, Karen K. TI EFFECT OF GROWTH HORMONE REPLACEMENT THERAPY ON THE QUALITY OF LIFE IN WOMEN WITH GROWTH HORMONE DEFICIENCY WHO HAVE A HISTORY OF ACROMEGALY VERSUS OTHER DISORDERS SO ENDOCRINE PRACTICE LA English DT Article ID ADULT GH DEFICIENCY; LONG-TERM CURE; MYOCARDIAL-INFARCTION; FOLLOW-UP; TRIAL; HYPOPITUITARISM; QUESTIONNAIRE; IMPAIRMENTS; DIAGNOSIS; DISEASE AB Objective: To compare the response in quality of life (QoL) to growth hormone (GH) replacement in women with GH deficiency (GHD) and a history of acromegaly with that in women with GHD of other causes. Methods: Fifty-five women with GHD were studied: 17 with prior acromegaly and 38 with other causes of GHD. We compared two 6-month, randomized, placebo-controlled studies of GM therapy in women with hypopituitarism conducted with use of the same design-one in women with a history of acromegaly and one in women with no prior acromegaly. QoL was assessed with the following questionnaires: the QoL-Assessment of Growth Hormone Deficiency in Adults (AGHDA), the Symptom Questionnaire, and the 36-Item Short-Form Health Survey (SF-36). Results: The 2 groups had comparable mean pretreatment age, body mass index, and QoL scores and comparable mean GH dose at 6 months (0.61 +/- 0.30 versus 0.67 +/- 0.27 mg daily). After 6 months of GH replacement therapy, women with GHD and prior acromegaly demonstrated a greater improvement in AGHDA score, four SF-36 subscales (Role Limitations due to Physical Health, Energy or Fatigue, Emotional Well-Being, and Social Functioning), and the Somatic Symptoms subscale of the Symptom Questionnaire than did women with GHD of other causes. Poorer pretreatment QoL was associated with a greater improvement in QoL after administration of GH. Conclusion: In this study, GM replacement therapy improved QoL in women with GHD and a history of acromegaly but not in women with GHD due to other hypothalamic and pituitary disorders. Further studies are needed to determine the long-term risks versus benefits of GH replacement in patients who develop GHD after definitive treatment for acromegaly. (Endocr Pract. 2012;18:209-218) C1 [Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM KKMiller@Partners.org FU National Institutes of Health [MO1 RR01066, ULI RR02578]; Pfizer Inc.; Guthart Family Foundation FX We thank the nurses of the Massachusetts General Hospital General Clinical Research Center and the Harvard Catalyst Clinical Translational Science Center as well as the patients who participated in this study. This work was supported in part by the following grants: National Institutes of Health grants MO1 RR01066 and ULI RR02578, an investigator-initiated grant from Pfizer Inc., and a grant from the Guthart Family Foundation. NR 29 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD MAR-APR PY 2012 VL 18 IS 2 BP 209 EP 218 DI 10.4158/EP11134.OR PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929AL UT WOS:000303033500013 PM 22440981 ER PT J AU Azim, H Kroman, N Ameye, L Rotmensz, N Gelber, S Cordoba, O Pinto, A Jensen, M de Azambuja, E Peccatori, F AF Azim, H., Jr. Kroman, N. Ameye, L. Rotmensz, N. Gelber, S. Cordoba, O. Pinto, A. Jensen, M. de Azambuja, E. Peccatori, F. TI Pregnancy Following Estrogen Receptor-Positive Breast Cancer is Safe - Results From a Large Multi-center Case-control Study SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 8th European Breast Cancer Conference (EBCC) CY MAR 21-24, 2012 CL Vienna, AUSTRIA SP European Canc Org (ECCO) C1 [Azim, H., Jr.] Inst Jules Bordet, Breast Canc Translat Res Lab, B-1000 Brussels, Belgium. [Kroman, N.; Jensen, M.] Danish Breast Canc Cooperat Grp, Copenhagen, Denmark. [Ameye, L.] Inst Jules Bordet, Ctr Data, B-1000 Brussels, Belgium. [Rotmensz, N.] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy. [Cordoba, O.] Hosp Valle De Hebron, Barcelona, Spain. [Gelber, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pinto, A.] Univ La Paz, Madrid, Spain. [Peccatori, F.] European Inst Oncol, Fertil & Procreat Unit, Milan, Italy. RI Cordoba, Octavi/C-5613-2014 OI Cordoba, Octavi/0000-0002-9591-7430 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2012 VL 48 SU 1 BP S46 EP S46 PG 1 WC Oncology SC Oncology GA 926AV UT WOS:000302804600035 ER PT J AU Baselga, J Costa, F Gomez, H Hudis, C Rapoport, B Roche, H Schwartzberg, LS Petrenciuc, O Shan, M Gradishar, WJ AF Baselga, J. Costa, F. Gomez, H. Hudis, C. Rapoport, B. Roche, H. Schwartzberg, L. S. Petrenciuc, O. Shan, M. Gradishar, W. J. TI Design of RESILIENCE: a Phase 3 TRial Comparing CapecitabinE in Combination with SorafenIb or PLacebo for Treatment of Locally Advanced or MetastatIc HER2-Negative Breast CancEr SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 8th European Breast Cancer Conference (EBCC) CY MAR 21-24, 2012 CL Vienna, AUSTRIA SP European Canc Org (ECCO) C1 [Baselga, J.] Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. [Costa, F.] Hosp Sirio Libanes, Dept Oncol, Sao Paulo, Brazil. [Gomez, H.] Inst Nacl Enfermedades Neoplas, Dept Oncol, Lima, Peru. [Hudis, C.] Mem Sloan Kettering Canc Ctr, Dept Oncol, New York, NY 10021 USA. [Rapoport, B.] Med Oncol Ctr Rosebank, Dept Oncol, Johannesburg, South Africa. [Roche, H.] Inst Claudius Regaud, Dept Oncol, Toulouse, France. [Schwartzberg, L. S.] West Clin, Dept Oncol, Memphis, TN USA. [Petrenciuc, O.] Bayer HealthCare Pharmaceut, Dept Oncol, Toronto, ON, Canada. [Shan, M.] Bayer HealthCare Pharmaceut, Dept Oncol, Montville, NJ USA. [Gradishar, W. J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RI Roche, Henri/O-9211-2014 OI Roche, Henri/0000-0001-7463-205X NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2012 VL 48 SU 1 BP S117 EP S117 PG 1 WC Oncology SC Oncology GA 926AV UT WOS:000302804600266 ER PT J AU Cardoso, F Winer, E Norton, L Gomis, R Krop, I Harbeck, N Costa, A AF Cardoso, Fatima Winer, Eric Norton, Larry Gomis, Roger Krop, Ian Harbeck, Nadia Costa, Alberto TI Can an international consensus meeting change the future of advanced breast cancer patients? Highlights from ABC1 Consensus Meeting SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 8th European Breast Cancer Conference (EBCC) CY MAR 21-24, 2012 CL Vienna, AUSTRIA SP European Canc Org (ECCO) C1 [Cardoso, Fatima] Milan & Champalimaud Canc Ctr, European Sch Oncol, Lisbon, Portugal. [Winer, Eric] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. [Norton, Larry] Mem Sloan Kettering Canc Ctr, Div Solid Tumor Oncol, New York, NY 10021 USA. [Norton, Larry] Mem Sloan Kettering Canc Ctr, Breast Canc Program, New York, NY 10021 USA. [Gomis, Roger] Inst Res Biomed, Growth Control & Canc Metastasis Programme, Barcelona, Spain. [Krop, Ian] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. [Harbeck, Nadia] Univ Munich, Klinikum Grosshadern, D-80539 Munich, Germany. [Costa, Alberto] European Sch Oncol, Milan & Maugeri Fdn Breast Unit, Pavia, Italy. NR 7 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2012 VL 48 SU 1 BP S13 EP S14 PG 2 WC Oncology SC Oncology GA 926AV UT WOS:000302804600007 ER PT J AU Gnant, M Hortobagyi, GN Rugo, H Burris, HA Noguchi, S Pritchard, KI Baselga, J Sahmoud, T Bauly, H Piccart, M AF Gnant, M. Hortobagyi, G. N. Rugo, H. Burris, H. A. Noguchi, S. Pritchard, K. I. Baselga, J. Sahmoud, T. Bauly, H. Piccart, M. TI Everolimus Added to Exemestane Reduced Bone Markers in Postmenopausal Women with Advanced Breast Cancer (ABC): the BOLERO-2 Trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 8th European Breast Cancer Conference (EBCC) CY MAR 21-24, 2012 CL Vienna, AUSTRIA SP European Canc Org (ECCO) C1 [Gnant, M.] Med Univ Vienna, Dept Surg, Vienna, Austria. [Hortobagyi, G. N.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Rugo, H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Burris, H. A.] Sarah Cannon Res Inst, Drug Dev Program, Nashville, TN USA. [Noguchi, S.] Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan. [Pritchard, K. I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Pritchard, K. I.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Baselga, J.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA. [Sahmoud, T.] Novartis Pharmaceut, Global Oncol Dept, Florham Pk, NJ USA. [Bauly, H.] Novartis Pharma AG, Biostat, Basel, Switzerland. [Piccart, M.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2012 VL 48 SU 1 BP S43 EP S43 PG 1 WC Oncology SC Oncology GA 926AV UT WOS:000302804600026 ER PT J AU Ligibel, J Cirrincione, C Citron, M Ingle, J Gradishar, W Martino, S Hudis, C Winer, E Berry, D AF Ligibel, J. Cirrincione, C. Citron, M. Ingle, J. Gradishar, W. Martino, S. Hudis, C. Winer, E. Berry, D. TI Relationship Between Body Mass Index (BMI) and Outcomes in Node-positive Breast Cancer Patients Receiving Chemotherapy - Results From CALGB/Intergroup 9741 SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 8th European Breast Cancer Conference (EBCC) CY MAR 21-24, 2012 CL Vienna, AUSTRIA SP European Canc Org (ECCO) C1 [Ligibel, J.; Winer, E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cirrincione, C.] Duke Univ, Durham, NC USA. [Citron, M.] LIJ Sch Med, Lake Success, NY USA. [Ingle, J.] Mayo Clin, Rochester, MN USA. [Gradishar, W.] Robert Lurie Comprehens Canc Ctr, Chicago, IL USA. [Martino, S.] Angels Clin, Los Angeles, CA USA. [Hudis, C.] Mem Sloane Kettering Canc Ctr, New York, NY USA. [Berry, D.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2012 VL 48 SU 1 BP S166 EP S167 PG 2 WC Oncology SC Oncology GA 926AV UT WOS:000302804600421 ER PT J AU Rugo, H Pritchard, KI Gnant, M Noguchi, S Piccart, M Hortobagyi, GN Burris, HA Bauly, H Sahmoud, T Baselga, J AF Rugo, H. Pritchard, K. I. Gnant, M. Noguchi, S. Piccart, M. Hortobagyi, G. N. Burris, H. A. Bauly, H. Sahmoud, T. Baselga, J. TI Everolimus (EVE) for Postmenopausal Women with Advanced Breast Cancer (ABC) Refractory to Letrozole or Anastrozole: Long-term Efficacy and Safety Results of the BOLERO-2 Trial SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract CT 8th European Breast Cancer Conference (EBCC) CY MAR 21-24, 2012 CL Vienna, AUSTRIA SP European Canc Org (ECCO) C1 [Rugo, H.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Pritchard, K. I.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Pritchard, K. I.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Gnant, M.] Med Univ Vienna, Dept Surg, Vienna, Austria. [Noguchi, S.] Osaka Univ, Dept Breast & Endocrine Surg, Osaka, Japan. [Piccart, M.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. [Hortobagyi, G. N.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Burris, H. A.] Sarah Cannon Res Inst, Drug Dev Program, Nashville, TN USA. [Bauly, H.] Novartis Pharma AG, Biostat, Basel, Switzerland. [Sahmoud, T.] Novartis Pharmaceut, Global Oncol Dev, Florham Pk, NJ USA. [Baselga, J.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2012 VL 48 SU 1 BP S116 EP S116 PG 1 WC Oncology SC Oncology GA 926AV UT WOS:000302804600262 ER PT J AU Freudenreich, O Kontos, N Querques, J AF Freudenreich, Oliver Kontos, Nicholas Querques, John TI Psychiatric Polypharmacy: A Clinical Approach Based on Etiology and Differential Diagnosis SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE differential diagnosis; etiology; polypharmacy; professionalism ID 1ST-EPISODE SCHIZOPHRENIA; ILLNESS BEHAVIOR; MONOTHERAPY; MEDICATION; METAANALYSIS; PHYSICIANS; OUTCOMES; THERAPY; TRIAL; CARE AB Polypharmacy is common clinical practice in the United States for many psychiatric conditions and for many reasons. In this article we encourage clinicians to use the familiar practice of differential diagnosis to systematically identify etiological factors contributing to polypharmacy. We offer a clinical approach based on (1) reviewing the four main factors responsible for polypharmacy (the disease, the patient, the physician, and society) and (2) answering two questions about optimizing medication regimens (What can I do without explicit permission from the patient or others? What can I do with permission from them?). We contend that all physicians share a professional responsibility for prescribing medications judiciously because unnecessary prescribing exposes patients to unwarranted risks and squanders valuable and scarce resources. Psychiatrists can ask themselves a Kantian question: would my way of prescribing lead to good, socially acceptable outcomes if followed by all physicians treating similar patients? (HARV REV PSYCHIATRY 2012;20:79-85.) C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Freudenreich, O (reprint author), Erich Lindemann Mental Hlth Ctr, Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM ofreudenreich@partners.org NR 39 TC 2 Z9 2 U1 2 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2012 VL 20 IS 2 BP 79 EP 85 DI 10.3109/10673229.2012.677358 PG 7 WC Psychiatry SC Psychiatry GA 927ZJ UT WOS:000302948900001 PM 22512741 ER PT J AU Judge, AM AF Judge, Abigail M. TI "Sexting" Among US Adolescents: Psychological and Legal Perspectives SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE adolescent psychology; law; sexting; sexual behavior ID PARENTAL COMMUNICATION; OBJECTIFICATION THEORY; SELF-OBJECTIFICATION; SEX; PERFORMANCE; EXPERIENCES; SWIMSUIT; CHILDREN; PEERS; BRAIN AB This article will discuss the phenomenon of "sexting" (i.e., the exchange of sexually explicit images between adolescents via cell phone) in the United States, with a particular focus on clinical and legal implications. Although sexting is frequently discussed in the popular press, there is virtually no scientific literature available on this topic. In contrast, the legal literature has discussed sexting more comprehensively due to the implications of child pornography statutes for the social response to involved youth. This article will consider sexting from a clinical and legal perspective, and recommend ways to understand and address this practice clinically with adolescent patients. (HARV REV PSYCHIATRY 2012;20:86-96.) C1 [Judge, Abigail M.] Harvard Univ, Sch Med, Boston, MA USA. [Judge, Abigail M.] Massachusetts Gen Hosp, Children & Law Program, Boston, MA 02114 USA. RP Judge, AM (reprint author), 1218 Massachusetts Ave, Cambridge, MA 02138 USA. EM abigailjudge@abigailjudge.com NR 59 TC 12 Z9 12 U1 2 U2 19 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2012 VL 20 IS 2 BP 86 EP 96 DI 10.3109/10673229.2012.677360 PG 11 WC Psychiatry SC Psychiatry GA 927ZJ UT WOS:000302948900002 PM 22512742 ER PT J AU Adler, KA Stark, M Choi-Kain, LW Marouf, F AF Adler, Karen A. Stark, Martha Choi-Kain, Lois W. Marouf, Feyza TI "Something Is Better Than Nothing": Psychotherapy with an Older Woman SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE aging; personality disorder; psychotherapy C1 [Adler, Karen A.; Choi-Kain, Lois W.] McLean Hosp, Belmont, MA 02478 USA. [Adler, Karen A.; Choi-Kain, Lois W.] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Stark, Martha] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Marouf, Feyza] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Adler, KA (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. EM kadler@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2012 VL 20 IS 2 BP 109 EP 118 DI 10.3109/10673229.2012.677356 PG 10 WC Psychiatry SC Psychiatry GA 927ZJ UT WOS:000302948900004 PM 22512744 ER PT J AU Wray, LO Szymanski, BR Kearney, LK McCarthy, JF AF Wray, Laura O. Szymanski, Benjamin R. Kearney, Lisa K. McCarthy, John F. TI Implementation of Primary Care-Mental Health Integration Services in the Veterans Health Administration: Program Activity and Associations with Engagement in Specialty Mental Health Services SO JOURNAL OF CLINICAL PSYCHOLOGY IN MEDICAL SETTINGS LA English DT Article DE Primary care; Mental health; Engagement; Veterans ID RISK ALCOHOL-USE; COLLABORATIVE CARE; RANDOMIZED-TRIAL; TERM OUTCOMES; REFERRAL CARE; OLDER-ADULTS; PRISM-E; DEPRESSION; MANAGEMENT; SYSTEM AB This paper describes the status of the Veterans Health Administration (VHA) Primary Care-Mental Health Integration (PC-MHI) services implementation and presents an assessment of associations between receipt of PC-MHI services and likelihood of receiving a second specialty mental health (SMH) appointment following an initial SMH encounter. The total PC-MHI service recipients and encounters/month rose substantially between October 2007 and April 2011. Adjusting for important covariates, the likelihood of receiving a second SMH encounter within 3 months of an index SMH appointment was 1.37 times greater among individuals who had received a PC-MHI encounter within 3 months of the initial SMH appointment. Implementation of VHA PC-MHI services has substantially increased VHA capacity to deliver mental health services in primary care and findings indicate that PC-MHI services are associated with greater engagement in SMH treatment. Implementation of VHA PC-MHI services is progressing with new technical assistance strategies being deployed. C1 [Wray, Laura O.] US Dept Vet Affairs, Ctr Integrated Healthcare, Buffalo, NY 14215 USA. [Wray, Laura O.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Med, Buffalo, NY 14260 USA. [Szymanski, Benjamin R.; McCarthy, John F.] US Dept Vet Affairs, Off Mental Hlth Operat, Serious Mental Illness Treatment Resource & Evalu, Ann Arbor, MI USA. [Kearney, Lisa K.] US Dept Vet Affairs, Off Mental Hlth Operat, Washington, DC USA. [Kearney, Lisa K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [McCarthy, John F.] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI USA. RP Wray, LO (reprint author), US Dept Vet Affairs, Ctr Integrated Healthcare, VAWNYHS 116 N,3495 Bailey Ave, Buffalo, NY 14215 USA. EM Laura.wray@va.gov NR 41 TC 36 Z9 36 U1 2 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9583 J9 J CLIN PSYCHOL MED S JI J. Clin. Psychol. Med. Settings PD MAR PY 2012 VL 19 IS 1 BP 105 EP 116 DI 10.1007/s10880-011-9285-9 PG 12 WC Psychology, Clinical SC Psychology GA 925PC UT WOS:000302772300012 PM 22383016 ER PT J AU Gruenewald, DA AF Gruenewald, David A. TI Can Health Care Rationing Ever Be Rational? SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID DECISION-MAKING; MEDICAL-CARE; END; AGE; INFORMATION; CANCER; PHYSICIANS; REFORM; OLDER AB Americans' appetite for life-prolonging therapies has led to unsustainable growth in health care costs. It is tempting to target older people for health care rationing based on their disproportionate use of health care resources and lifespan already lived, but aged-based rationing is unacceptable to many. Systems reforms can improve the efficiency of health care and may lessen pressure to ration services, but difficult choices still must be made to limit expensive, marginally beneficial interventions. In the absence of agreement on principles to govern health care resource allocation, a fair, open priority-setting process should be created to allow for reasonable disagreement on principles while being seen as legitimate by all stakeholders. At the patient-care level, careful discussions about the benefits and burdens of medical intervention and support for slow medicine a gentle, family-centered care approach for frail elders can do much to avoid harming these patients with aggressive yet unwanted medical care while reducing wasteful spending. C1 [Gruenewald, David A.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Gruenewald, David A.] VA Puget Sound Hlth Care Syst, Palliat Care & Hosp Serv, Seattle, WA USA. RP Gruenewald, DA (reprint author), Univ Washington, Sch Med, Seattle, WA 98195 USA. RI Embrett, Mark/H-4466-2014 OI Embrett, Mark/0000-0002-3969-0219 NR 42 TC 8 Z9 8 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 2012 VL 40 IS 1 BP 17 EP 25 DI 10.1111/j.1748-720X.2012.00641.x PG 9 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 915ZB UT WOS:000302065100003 PM 22458458 ER PT J AU Rasetshwane, DM Neely, ST Allen, JB Shera, CA AF Rasetshwane, Daniel M. Neely, Stephen T. Allen, Jont B. Shera, Christopher A. TI Reflectance of acoustic horns and solution of the inverse problem SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID VOCAL-TRACT SHAPE; IMPEDANCE; PROPAGATION; COEFFICIENT; EQUATION; LINES AB A method is described for solving the inverse problem of determining the profile of an acoustic horn when time-domain reflectance (TDR) is known only at the entrance. The method involves recasting Webster's horn equation in terms of forward and backward propagating wave variables. An essential feature of this method is a requirement that the backward propagating wave be continuous at the wave-front at all locations beyond the entrance. Derivation of the inverse solution raises questions about the meaning of causality in the context of wave propagation in non-uniform tubes. Exact reflectance expressions are presented for infinite exponential, conical and parabolic horns based on exact solutions of the horn equation. Diameter functions obtained with the inverse solution are a good match to all three horn profiles. (C) 2012 Acoustical Society of America. [DOI: 10.1121/1.3681923] C1 [Rasetshwane, Daniel M.; Neely, Stephen T.] Boys Town Natl Res Hosp, Omaha, NE 68131 USA. [Allen, Jont B.] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. RP Rasetshwane, DM (reprint author), Boys Town Natl Res Hosp, 555 N 30th St, Omaha, NE 68131 USA. EM daniel.rasetshwane@boystown.org OI Neely, Stephen/0000-0002-1349-5386 FU NIH [R01 DC08318, R01 DC03687] FX Research was supported by grants from NIH [R01 DC08318 (S.T.N.) and R01 DC03687 (C.A.S.)] We would like to thank Roger D. Serwy for stimulating discussions regarding the inverse solution of Caflisch (1981). NR 25 TC 5 Z9 5 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAR PY 2012 VL 131 IS 3 BP 1863 EP 1873 DI 10.1121/1.3681923 PN 1 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 911LV UT WOS:000301719200017 PM 22423684 ER PT J AU Chambliss, WG Carroll, WA Kennedy, D Levine, D Mone, MA Ried, LD Shepherd, M Yelvigi, M AF Chambliss, Walter G. Carroll, Wesley A. Kennedy, Daniel Levine, Donald Mone, Michael A. Ried, L. Douglas Shepherd, Marv Yelvigi, Mukund TI Role of the pharmacist in preventing distribution of counterfeit medications SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Editorial Material DE Counterfeiting (drug); drug products; technology; pedigree AB Objective: To provide an overview of the counterfeit medication problem and recommendations of a joint American Pharmacists Association (APhA) Academy of Pharmaceutical Research and Science and APhA Academy of Pharmacy Practice and Management taskforce. Date sources: SciFinder and PubMed were searched from 1980 to March 2011 using the following keywords: counterfeit drug product, counterfeit medications, drug product authentication, drug product verification, and track-and-trace. Publications, presentations, and websites of organizations that research the counterfeit medication problem in the United States and other countries were reviewed. A representative from the security division of a pharmaceutical manufacturer and a representative from a supplier of anticounterfeiting technologies gave presentations to the taskforce. Summary: The taskforce recommends that pharmacists (1) purchase medications from known, reliable sources; (2) warn patients of the dangers of purchasing medications over the Internet; (3) confirm with distributors that products were purchased from manufacturers or other reliable sources; (4) monitor counterfeit product alerts; (5) examine products for suspicious appearance; (6) work with the pharmaceutical industry, distributors, and the Food and Drug Administration (FDA) to close gaps in the supply chain, especially for drugs in short supply; (7) use scanning technology in the pharmacy as part of a prescription verification process; (8) educate themselves, coworkers, and patients about the risks of counterfeit medications; and (9) report suspicious medications to FDA, the distributor, and the manufacturer. Conclusion: The consequence of a patient receiving a counterfeit medication in the United States could be catastrophic, and pharmacists must play an active role in preventing such an event from occurring. C1 [Chambliss, Walter G.] Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, University, MS 38677 USA. [Carroll, Wesley A.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Kennedy, Daniel] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Levine, Donald] Merck Consumer Care, World Wide Clin Supply, Memphis, TN USA. [Mone, Michael A.] Cardinal Hlth, Supply Chain Integr & Senior Regulatory Counsel, Qual & Regulatory Affairs, Dublin, OH USA. [Ried, L. Douglas] Univ S Florida, Coll Pharm, Tampa, FL USA. [Shepherd, Marv] Univ Texas Austin, Coll Pharm, Ctr Pharmacoecon Studies, Austin, TX 78712 USA. [Yelvigi, Mukund] Pfizer Inc, Clin Supply Chain Management, New York, NY USA. RP Chambliss, WG (reprint author), Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, 100 Barr Hall, University, MS 38677 USA. EM wchambli@olemiss.edu NR 24 TC 3 Z9 3 U1 0 U2 14 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD MAR-APR PY 2012 VL 52 IS 2 BP 195 EP 199 DI 10.1331/JAPhA.2012.11085 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 927AS UT WOS:000302877900011 PM 22370383 ER PT J AU Eshghi, A Pinne, M Haake, DA Zuerner, RL Frank, A Cameron, CE AF Eshghi, Azad Pinne, Marija Haake, David A. Zuerner, Richard L. Frank, Ami Cameron, Caroline E. TI Methylation and in vivo expression of the surface-exposed Leptospira interrogans outer-membrane protein OmpL32 SO MICROBIOLOGY-SGM LA English DT Article ID SECONDARY STRUCTURE PREDICTION; HEPARIN-BINDING HEMAGGLUTININ; ESCHERICHIA-COLI; PATHOGENIC LEPTOSPIRA; RICKETTSIA-PROWAZEKII; BACTERIAL CHEMOTAXIS; PROTEOMIC ANALYSIS; RELEASE FACTORS; VIRULENCE; IDENTIFICATION AB Recent studies have revealed that bacterial protein methylation is a widespread post-translational modification that is required for virulence in selected pathogenic bacteria. In particular, altered methylation of outer-membrane proteins has been shown to modulate the effectiveness of the host immune response. In this study, 2D gel electrophoresis combined with MALDI-TOF MS identified a Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 protein, corresponding to ORF LIC11848, which undergoes extensive and differential methylation of glutamic acid residues. Immunofluorescence microscopy implicated LIC11848 as a surface-exposed outer-membrane protein, prompting the designation OmpL32. Indirect immunofluorescence microscopy of golden Syrian hamster liver and kidney sections revealed expression of OmpL32 during colonization of these organs. Identification of methylated surface-exposed outer-membrane proteins, such as OmpL32, provides a foundation for delineating the role of this post-translational modification in leptospiral virulence. C1 [Eshghi, Azad; Cameron, Caroline E.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. [Pinne, Marija] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Pinne, Marija; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Zuerner, Richard L.; Frank, Ami] ARS, Infect Bacterial Dis Res Unit, NADC, USDA, Ames, IA USA. RP Cameron, CE (reprint author), Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada. EM caroc@uvic.ca FU University of Victoria; Pacific Century Graduate Scholarship; Natural Sciences and Engineering Research Council of Canada [327186]; British Columbia Proteomics Network; Canada Foundation for Innovation; British Columbia Knowledge Development Fund; VA; Public Health Service from the National Institute of Allergy and Infectious Diseases [AI-034431] FX The authors would like to thank Dr Martin Boulanger, University of Victoria, Victoria, BC, Canada, for his gift of the pET28a vector and assistance with construct design, Anna von Rossum and Marcus Barron for assistance with recombinant protein production, and Dr Christoph Borchers, Derek Smith, Jen Proc, Leanne Ohlund, Darryl Hardie and the members of the University of Victoria-Genome BC Proteomics Centre for their support and guidance with the proteomic analyses. This work was supported by a University of Victoria Fellowship, Graduate Scholarship and the Pacific Century Graduate Scholarship (A. E.), a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (327186; C. E. C.), the British Columbia Proteomics Network (C. E. C.), the Canada Foundation for Innovation (C. E. C.), the British Columbia Knowledge Development Fund (C. E. C.), VA Medical Research Funds (D. A. H.), and Public Health Service grant AI-034431 (D. A. H.) from the National Institute of Allergy and Infectious Diseases. C. E. C. is a Canada Research Chair in Molecular Pathogenesis and a Michael Smith Foundation for Health Research Scholar. NR 71 TC 11 Z9 11 U1 2 U2 17 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD MAR PY 2012 VL 158 BP 622 EP 635 DI 10.1099/mic.0.054767-0 PN 3 PG 14 WC Microbiology SC Microbiology GA 926II UT WOS:000302824100004 PM 22174381 ER PT J AU Reiner, T Lacy, J Keliher, EJ Yang, KS Ullal, A Kohler, RH Vinegoni, C Weissleder, R AF Reiner, Thomas Lacy, Jessica Keliher, Edmund J. Yang, Katherine S. Ullal, Adeeti Kohler, Rainer H. Vinegoni, Claudio Weissleder, Ralph TI Imaging Therapeutic PARP Inhibition In Vivo through Bioorthogonally Developed Companion Imaging Agents SO NEOPLASIA LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE; BREAST-CANCER; SKIN-FOLD; CHAMBER; OPTIMIZATION; MICROSCOPY; INVASION; TUMORS; MICE AB A number of small-molecule poly (ADP-ribose) polymerase (PARP) inhibitors are currently undergoing advanced clinical trials. Determining the distribution and target inhibitory activity of these drugs in individual subjects, however, has proven problematic. Here, we used a PARP agent for positron emission tomography-computed tomography (PET-CT) imaging (F-18-BO), which we developed based on the Olaparib scaffold using rapid bioorthogonal conjugation chemistries. We show that the bioorthogonal F-18 modification of the parent molecule is simple, highly efficient, and well tolerated, resulting in a half maximal inhibitory concentration (IC50) of 17.9 +/- 1.1 nM. Intravital imaging showed ubiquitous distribution of the drug and uptake into cancer cells, with ultimate localization within the nucleus, all of which were inhibitable. Whole-body PET-CT imaging showed tumoral uptake of the drug, which decreased significantly, after a daily dose of Olaparib. Standard F-18-fludeoxyglucose imaging, however, failed to detect such therapy-induced changes. This research represents a step toward developing a more generic approach for the rapid codevelopment of companion imaging agents based on small-molecule therapeutic inhibitors. C1 [Reiner, Thomas; Lacy, Jessica; Keliher, Edmund J.; Yang, Katherine S.; Ullal, Adeeti; Kohler, Rainer H.; Vinegoni, Claudio; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU National Institutes of Health [R01EB010011, P50CA86355, T32-CA79443]; German Academy of Sciences Leopoldina [LPDS 2009-24] FX This study was funded in part by National Institutes of Health grants R01EB010011 and P50CA86355 (R. W.). K. S. Yang was supported by a National Institutes of Health grant T32-CA79443, and T. Reiner was supported by a grant from the German Academy of Sciences Leopoldina (LPDS 2009-24). The authors have no conflicts of interest to declare. The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must therefore be hereby-marked advertisement in accordance with 18 U. S. C. Section 1734 solely to indicate this fact. NR 25 TC 34 Z9 34 U1 2 U2 14 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAR PY 2012 VL 14 IS 3 BP 169 EP + DI 10.1593/neo.12414 PG 12 WC Oncology SC Oncology GA 922HW UT WOS:000302539000001 PM 22496617 ER PT J AU Bishehsari, F Sharma, A Stello, K Toth, C O'Connell, MR Evans, AC LaRusch, J Muddana, V Papachristou, GI Whitcomb, DC AF Bishehsari, Faraz Sharma, Arun Stello, Kimberly Toth, Chad O'Connell, Michael Richard Evans, Anna C. LaRusch, Jessica Muddana, Venkata Papachristou, Georgios I. Whitcomb, David C. TI TNF-alpha gene (TNFA) variants increase risk for multi-organ dysfunction syndrome (MODS) in acute pancreatitis SO PANCREATOLOGY LA English DT Article DE Ystemic inflammatory response syndrome (SIRS); Genetic epidemiology; Shock; Modeling; Pancreas ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY RESPONSE SYNDROME; CYTOKINE CASCADE PROGRESSION; SMALL-MOLECULE INHIBITION; PROMOTER POLYMORPHISM; 5'-FLANKING REGION; CYSTIC-FIBROSIS; UNITED-STATES; SEVERITY; ASSOCIATION AB Background/Objectives: Acute pancreatitis (AP) is a complex inflammatory syndrome with unpredictable progression to systemic inflammation and multi-organ dysfunction syndrome (MODS). Tumor necrosis factor alpha (TNF-alpha) is a cytokine that may link inflammation to the systemic inflammatory response syndrome (SIRS), which usually precedes MODS. Small genetic cohort studies of the TNFA promoter in AP produced ambiguous results. We performed a comprehensive evaluation of TNFA promoter variants to assess both susceptibility to AP and risk of progression to MODS. Methods: We prospectively ascertained 401 controls and 211 patients with AP that were assessed for persistent SIRS (>48 h) and MODS. MODS was defined as failure of >= 2 organ systems (cardiovascular, pulmonary, and/or renal) persisting more than 48 h. Subjects were genotyped by DNA sequencing and analyzed for SNPs at -1031 C/T (rs1799964), -863 A/C (rs1800630), -857 C/T (rs1799724), -308 A/C (rs1800629), and -238 A/C (r5361525). Results: Twenty-three of 211 AP patients (11%) developed MODS. TNFA promoter variants were not associated with susceptibility to AP. but progression to MODS was associated with the minor allele at -1031C (56.5% vs. 32.4% P = 0.022, OR: 2.7: 95%CI: 1.12-6.51) and -863A (43.5% vs. 21.8% P = 0.022, OR: 2.76: 95%CI: 1.12-6.74). Conclusion: TNFA promoter variants do not alter susceptibility to AP, but rather the TNF-alpha expression-enhancing -1031C and -863A alleles significantly increased the risk of AP progression to MODS. These data, within the context of previous studies, clarify the risk of specific genetic variants in TNFA and therefore the role of TNF-alpha in the overall AP syndrome. Copyright (C) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. C1 [Bishehsari, Faraz; Stello, Kimberly; Toth, Chad; O'Connell, Michael Richard; LaRusch, Jessica; Muddana, Venkata; Papachristou, Georgios I.; Whitcomb, David C.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. [Whitcomb, David C.] Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA 15213 USA. [Whitcomb, David C.] Univ Pittsburgh, Dept Physiol, Pittsburgh, PA 15213 USA. [Bishehsari, Faraz; Stello, Kimberly; Toth, Chad; O'Connell, Michael Richard; LaRusch, Jessica; Muddana, Venkata; Papachristou, Georgios I.; Whitcomb, David C.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Sharma, Arun; Evans, Anna C.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Papachristou, Georgios I.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Whitcomb, DC (reprint author), UPMC Gastroenterol Hepatol & Nutr Adm, Room 401-4,3708 5th Ave, Pittsburgh, PA 15213 USA. EM whitcomb@pitt.edu FU Medical Student Research Training (MSRT [T32DK063922]; [R01 DK061451] FX The authors gratefully acknowledge the critical review of M Michael Barmada PhD and the editorial assistance of Michelle Kienholz. Arun Sharma was supported by Medical Student Research Training (MSRT) supplement to T32DK063922 (DCW). Jessica LaRusch PhD was supported by T32DK063922 (DCW). Genotyping was supported by R01 DK061451 (DCW). This project used the University of Pittsburgh Genomics and Proteomics Core Laboratory (UL1 RR024153) and the UPCI Clinical Genomics Immunoproteomics and Sequencing Facility (NIH P30CA047904). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or NIH. NR 41 TC 12 Z9 15 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PD MAR-APR PY 2012 VL 12 IS 2 BP 113 EP 118 DI 10.1016/j.pan.2012.02.014 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 929NY UT WOS:000303073800006 PM 22487520 ER PT J AU Gaal, EI Salo, P Kristiansson, K Rehnstrom, K Kettunen, J Sarin, AP Niemela, M Jula, A Raitakari, OT Lehtimaki, T Eriksson, JG Widen, E Gunel, M Kurki, M Fraunberg, MVZ Jaaskelainen, JE Hernesniemi, J Jarvelin, MR Pouta, A Newton-Cheh, C Salomaa, V Palotie, A Perola, M AF Gaal, Emilia Ilona Salo, Perttu Kristiansson, Kati Rehnstrom, Karola Kettunen, Johannes Sarin, Antti-Pekka Niemela, Mika Jula, Antti Raitakari, Olli T. Lehtimaki, Terho Eriksson, Johan G. Widen, Elisabeth Guenel, Murat Kurki, Mitja Fraunberg, Mikael von Und Zu Jaaskelainen, Juha E. Hernesniemi, Juha Jarvelin, Marjo-Riitta Pouta, Anneli Newton-Cheh, Christopher Salomaa, Veikko Palotie, Aarno Perola, Markus CA ICBP-GWAS TI Intracranial Aneurysm Risk Locus 5q23.2 Is Associated with Elevated Systolic Blood Pressure SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUBARACHNOID HEMORRHAGE; GENETIC-VARIANTS; CASE-FATALITY; DISEASE RISK; METAANALYSIS; IMPUTATION; PROLIFERATION; HYPERTENSION; AGE AB Although genome-wide association studies (GWAS) have identified hundreds of complex trait loci, the pathomechanisms of most remain elusive. Studying the genetics of risk factors predisposing to disease is an attractive approach to identify targets for functional studies. Intracranial aneurysms (IA) are rupture-prone pouches at cerebral artery branching sites. IA is a complex disease for which GWAS have identified five loci with strong association and a further 14 loci with suggestive association. To decipher potential underlying disease mechanisms, we tested whether there are IA loci that convey their effect through elevating blood pressure (BP), a strong risk factor of IA. We performed a meta-analysis of four population-based Finnish cohorts (n(FIN) = 11 266) not selected for IA, to assess the association of previously identified IA candidate loci (n = 19) with BP. We defined systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure as quantitative outcome variables. The most significant result was further tested for association in the ICBP-GWAS cohort of 200 000 individuals. We found that the suggestive IA locus at 5q23.2 in PRDM6 was significantly associated with SBP in individuals of European descent (p(FIN) = 3.01E-05, p(ICBP-GWAS) = 0.0007, p(ALL) = 8.13E-07). The risk allele of IA was associated with higher SBP. PRDM6 encodes a protein predominantly expressed in vascular smooth muscle cells. Our study connects a complex disease (IA) locus with a common risk factor for the disease (SBP). We hypothesize that common variants in PRDM6 can contribute to altered vascular wall structure, hence increasing SBP and predisposing to IA. True positive associations often fail to reach genome-wide significance in GWAS. Our findings show that analysis of traditional risk factors as intermediate phenotypes is an effective tool for deciphering hidden heritability. Further, we demonstrate that common disease loci identified in a population isolate may bear wider significance. C1 [Gaal, Emilia Ilona; Salo, Perttu; Kristiansson, Kati; Kettunen, Johannes; Sarin, Antti-Pekka; Jula, Antti; Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Publ Hlth Genom Unit, Helsinki, Finland. [Gaal, Emilia Ilona; Kristiansson, Kati; Rehnstrom, Karola; Kettunen, Johannes; Sarin, Antti-Pekka; Widen, Elisabeth; Palotie, Aarno; Perola, Markus] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Gaal, Emilia Ilona; Niemela, Mika; Hernesniemi, Juha] Univ Helsinki, Cent Hosp, Dept Neurosurg, Helsinki, Finland. [Rehnstrom, Karola; Palotie, Aarno] Wellcome Trust Sanger Inst, Hinxton, England. [Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli T.] Univ Turku, Dept Clin Physiol, Turku, Finland. [Raitakari, Olli T.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland. [Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland. [Eriksson, Johan G.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Diabet Unit, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Inst Clin Med, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. [Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland. [Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland. [Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland. [Guenel, Murat] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT USA. [Kurki, Mitja; Fraunberg, Mikael von Und Zu; Jaaskelainen, Juha E.] Kuopio Univ Hosp, Neurosurg NeuroCtr, SF-70210 Kuopio, Finland. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Biostat & Epidemiol, Sch Publ Hlth, Fac Med, London, England. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Jarvelin, Marjo-Riitta; Pouta, Anneli] Natl Inst Hlth & Welf, Dept Children Young People & Families, Oulu, Finland. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland. [Palotie, Aarno] Broad Inst Harvard & MIT, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA USA. [Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland. [Palotie, Aarno] Univ Cent Hosp, Helsinki, Finland. [Perola, Markus] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. RP Gaal, EI (reprint author), Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Publ Hlth Genom Unit, Helsinki, Finland. EM emilia.gaal@helsinki.fi RI EHRET, Georg/A-9532-2009; Niemela, Mika/F-2539-2015; OI EHRET, Georg/0000-0002-5730-0675; Niemela, Mika/0000-0003-1526-0684; Kristiansson, Kati/0000-0003-4688-107X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Eriksson, Johan/0000-0002-2516-2060 FU Orion-Farmos Research Foundation; Academy of Finland [250207, 129494, 129322, 129287, 134839, 120315, 129255, 129907, 135072, 114382, 126775, 127437, 129306, 130326, 209072, 210595, 213225, 216374, 126925, 121584, 124282, 129378, 117797, 41071, 104781, 1114194]; Finnish Foundation for Cardiovascular Research; Sigrid Juselius Foundation; Finnish Diabetes Research Society; Samfundet Folkhalsan; Juho Vainio Foundation; Novo Nordisk Foundation; Finska Lakaresallskapet; Paivikki and Sakari Sohlberg Foundation; Signe and Ane Gyllenberg Foundation; Yrjo Jahnsson Foundation; Social Insurance Institution of Finland; Kuopio, Tampere, and Turku University; Paavo Nurmi Foundation; Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; University Hospital Oulu, Biocenter [5R01HL087679-02]; University of Oulu, Finland, NHLBI [HEALTH-F4-2007-201413]; Medical Research Council [G0500539, G0600705]; Wellcome Trust, UK [GR069224] FX K Kristiansson was supported by the Orion-Farmos Research Foundation and the Academy of Finland (grant number 250207). V Salomaa and M Perola were supported by the Academy of Finland (grant numbers 129494 and 129322, respectively), the Finnish Foundation for Cardiovascular Research, and the Sigrid Juselius Foundation. E Widen was supported by the Academy of Finland (grants 129287, 134839 and 120315). JG Eriksson was supported by the Academy of Finland (grants 126775, 129255, 129907, and 135072). Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland (project numbers: 114382, 126775, 127437, 129255, 129306, 130326, 209072, 210595, 213225, and 216374), the Finnish Diabetes Research Society, the Finnish Foundation for Cardiovascular Research, the Samfundet Folkhalsan, the Juho Vainio Foundation, the Novo Nordisk Foundation, the Finska Lakaresallskapet, the Paivikki and Sakari Sohlberg Foundation, the Signe and Ane Gyllenberg Foundation, and the Yrjo Jahnsson Foundation. The Young Finns Study has been financially supported by the Academy of Finland (project numbers: 126925, 121584, 124282, 129378, 117797, and 41071), the Social Insurance Institution of Finland, Kuopio, Tampere, and Turku University Hospital Medical Funds, the Juho Vainio Foundation, the Paavo Nurmi Foundation, Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation, the Sigrid Juselius Foundation, Tampere Tuberculosis Foundation, and the Emil Aaltonen Foundation. The Northern Finland Birth Cohort 1966 received financial support from the Academy of Finland (project numbers: 104781, 120315, 1114194, and Center of Excellence in Complex Disease Genetics), University Hospital Oulu, Biocenter, University of Oulu, Finland, NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01), ENGAGE project and grant agreement HEALTH-F4-2007-201413, the Medical Research Council (studentship grant G0500539, centre grant G0600705), and the Wellcome Trust (project grant GR069224), UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 13 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 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAR PY 2012 VL 8 IS 3 AR e1002563 DI 10.1371/journal.pgen.1002563 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 918MV UT WOS:000302254800039 PM 22438818 ER PT J AU Lill, CM Roehr, JT McQueen, MB Kavvoura, FK Bagade, S Schjeide, BMM Schjeide, LM Meissner, E Zauft, U Allen, NC Liu, T Schilling, M Anderson, KJ Beecham, G Berg, D Biernacka, JM Brice, A DeStefano, AL Do, CB Eriksson, N Factor, SA Farrer, MJ Foroud, T Gasser, T Hamza, T Hardy, JA Heutink, P Hill-Burns, EM Klein, C Latourelle, JC Maraganore, DM Martin, ER Martinez, M Myers, RH Nalls, MA Pankratz, N Payami, H Satake, W Scott, WK Sharma, M Singleton, AB Stefansson, K Toda, T Tung, JY Vance, J Wood, NW Zabetian, CP Young, P Tanzi, RE Khoury, MJ Zipp, F Lehrach, H Ioannidis, JPA Bertram, L AF Lill, Christina M. Roehr, Johannes T. McQueen, Matthew B. Kavvoura, Fotini K. Bagade, Sachin Schjeide, Brit-Maren M. Schjeide, Leif M. Meissner, Esther Zauft, Ute Allen, Nicole C. Liu, Tian Schilling, Marcel Anderson, Kari J. Beecham, Gary Berg, Daniela Biernacka, Joanna M. Brice, Alexis DeStefano, Anita L. Do, Chuong B. Eriksson, Nicholas Factor, Stewart A. Farrer, Matthew J. Foroud, Tatiana Gasser, Thomas Hamza, Taye Hardy, John A. Heutink, Peter Hill-Burns, Erin M. Klein, Christine Latourelle, Jeanne C. Maraganore, Demetrius M. Martin, Eden R. Martinez, Maria Myers, Richard H. Nalls, Michael A. Pankratz, Nathan Payami, Haydeh Satake, Wataru Scott, William K. Sharma, Manu Singleton, Andrew B. Stefansson, Kari Toda, Tatsushi Tung, Joyce Y. Vance, Jeffery Wood, Nick W. Zabetian, Cyrus P. Young, Peter Tanzi, Rudolph E. Khoury, Muin J. Zipp, Frauke Lehrach, Hans Ioannidis, John P. A. Bertram, Lars CA Genetic Epidemiology Parkinson's IPDGC Parkinson's Dis GWAS Consortium WTCCC2 TI Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN; RISK-FACTORS; MUTATIONS; VARIANTS; SUSCEPTIBILITY; DATASETS; TRIALS; REGION; VPS35 C1 [Lill, Christina M.; Roehr, Johannes T.; Schjeide, Brit-Maren M.; Schjeide, Leif M.; Meissner, Esther; Zauft, Ute; Liu, Tian; Schilling, Marcel; Lehrach, Hans; Bertram, Lars] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, D-14195 Berlin, Germany. [Lill, Christina M.; Bagade, Sachin; Allen, Nicole C.; Tanzi, Rudolph E.; Bertram, Lars] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Lill, Christina M.; Zipp, Frauke] Johannes Gutenberg Univ Mainz, Dept Neurol, Med Ctr, Mainz, Germany. [Lill, Christina M.; Young, Peter] Univ Hosp, Dept Neurol, Munster, Germany. [Roehr, Johannes T.; Schilling, Marcel] Free Univ Berlin, Dept Math & Comp Sci, Berlin, Germany. [McQueen, Matthew B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Kavvoura, Fotini K.; Ioannidis, John P. A.] Univ Ioannina, Sch Med, Clin & Mol Epidemiol Unit, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Kavvoura, Fotini K.] Royal Berkshire Hosp, Ctr Diabet & Endocrinol, Reading RG1 5AN, Berks, England. [Kavvoura, Fotini K.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Churchill Hosp, Oxford, England. [Liu, Tian] Max Planck Inst Human Dev, Berlin, Germany. [Anderson, Kari J.; Biernacka, Joanna M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Beecham, Gary; Martin, Eden R.; Scott, William K.; Vance, Jeffery] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA. [Berg, Daniela; Gasser, Thomas; Sharma, Manu] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany. [Berg, Daniela; Gasser, Thomas; Sharma, Manu] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany. [Brice, Alexis] INSERM, UMR S975, Paris, France. [Brice, Alexis] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, UMR S975, Paris, France. [Brice, Alexis] CNRS, UMR 7225, Paris, France. [Brice, Alexis] Hop La Pitie Salpetriere, AP HP, Dept Genet & Cytogenet, Paris, France. [DeStefano, Anita L.; Latourelle, Jeanne C.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Do, Chuong B.; Eriksson, Nicholas; Tung, Joyce Y.] 23andMe, Mountain View, CA USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. [Farrer, Matthew J.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Foroud, Tatiana; Pankratz, Nathan] Indiana Univ Sch Med, Indianapolis, IN USA. [Hamza, Taye; Hill-Burns, Erin M.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Hardy, John A.; Wood, Nick W.] UCL, Dept Mol Neurosci, UCL Inst Neurol, London, England. [Heutink, Peter] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Sect Med Genom, Amsterdam, Netherlands. [Klein, Christine] Univ Lubeck, Sect Clin & Mol Neurogenet, Dept Neurol, Lubeck, Germany. [Maraganore, Demetrius M.] NorthShore Univ Hlth Syst, Dept Neurol, Evanston, IL USA. [Martinez, Maria] Fac Med Toulouse, INSERM, UMR 1043, CPTP, F-31073 Toulouse, France. [Martinez, Maria] Univ Toulouse 3, F-31062 Toulouse, France. [Nalls, Michael A.; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Satake, Wataru; Toda, Tatsushi] Kobe Univ, Grad Sch Med, Div Neurol Mol Brain Sci, Kobe, Hyogo 657, Japan. [Wood, Nick W.] UCL, UCL Genet Inst, London, England. [Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Zabetian, Cyrus P.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Ioannidis, John P. A.] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modeling, Boston, MA 02111 USA. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Med, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Lill, CM (reprint author), Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, Ihnestr 73, D-14195 Berlin, Germany. EM lbertram@molgen.mpg.de RI Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; Traynor, Bryan/G-5690-2010; Schilling, Marcel/O-3169-2013; Zipp, Frauke/C-9968-2015; Lill, Christina/J-9449-2015; Bertram, Lars/K-3889-2015; Martinez, Maria/B-3111-2013; Wood, Nicholas/C-2505-2009; OI Zabetian, Cyrus/0000-0002-7739-4306; Schilling, Marcel/0000-0002-3453-7792; Zipp, Frauke/0000-0002-1231-1928; Lill, Christina/0000-0002-2805-1307; Bertram, Lars/0000-0002-0108-124X; Martinez, Maria/0000-0003-2180-4537; Wood, Nicholas/0000-0002-9500-3348; Latourelle, Jeanne/0000-0002-4218-9572; Myers, Richard/0000-0002-8365-2674; Burns, Gully/0000-0003-1493-865X FU Michael J. Fox Foundation for Parkinson's Disease (MJFF); Cure Alzheimer's Fund (CAF); National Alliance for Research on Schizophrenia and Depression (NARSAD); Prize4Life; EMD Serono; Deutscher Akademischer Austauschdienst (DAAD); Fidelity Biosciences Research Initiative (FBRI); German Ministry for Education and Research (BMBF); Tufts Clinical and Translational Science Institute (Tufts CTSI); National Institute of Health/National Center for Research Resources [UL1 RR025752]; Michael J. Fox Foundation; Edmond J. Safra Michael J. Fox Foundation Global Genetics Consortium Initiative; NIH [R01 NS 036960, R01CA141668, R01NS37167, 2R01 ES10751]; National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services [Z01 AG000949-02, Z01-ES101986]; U.S. Department of Defense [W81XWH-09-2-0128]; Volkswagen Foundation; Hermann and Lilly Schilling Foundation; Alnylam Pharmaceuticals; Medtronic; NorthShore University Health System; Cephalon; Merck-Serono; Novartis; Eisai; Mayo Clinic; deCODE FX The main funding for this study was provided by the Michael J. Fox Foundation for Parkinson's Disease (MJFF) with additional financial support by the Cure Alzheimer's Fund (CAF), the National Alliance for Research on Schizophrenia and Depression (NARSAD), Prize4Life, and EMD Serono (all to L Bertram). CM Lill was supported by a fellowship from the Deutscher Akademischer Austauschdienst (DAAD) and Fidelity Biosciences Research Initiative (FBRI). L Bertram is also supported by the German Ministry for Education and Research (BMBF). JPA Ioannidis was supported through the Tufts Clinical and Translational Science Institute (Tufts CTSI) under funding from the National Institute of Health/National Center for Research Resources (UL1 RR025752). Points of view or opinions in this paper are those of the authors and do not necessarily represent the official position or policies of the Tufts CTSI. M Sharma was supported by the Michael J. Fox Foundation. The NeuroGenetics Research Consortium GWAS [15] was funded by the Edmond J. Safra Michael J. Fox Foundation Global Genetics Consortium Initiative and NIH R01 NS 036960. The work of the International Parkinson's Disease Genomics Consortium (IPDGC) was supported in part by the Intramural Research Programs of the National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services: project numbers Z01 AG000949-02 and Z01-ES101986. In addition the work of the IPDGC was supported by the U.S. Department of Defense, award number W81XWH-09-2-0128. Portions of the work of the IPDGC utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, Md. (http://biowulf.nih.gov). T Foroud received funds from the National Institutes of Health (R01CA141668 and R01NS37167). C Klein is the recipient of a career development award from the Volkswagen Foundation and from the Hermann and Lilly Schilling Foundation. DM Maraganore acknowledges active funding support from the National Institutes of Health (2R01 ES10751), Alnylam Pharmaceuticals, Medtronic, and NorthShore University Health System. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; CB Do, N Eriksson, and JY Tung are employed by 23andMe and own stock options in the company. MJ Farrer and Mayo Foundation received royalties from H. Lundbeck A/S and Isis Pharmaceuticals. In addition, MJ Farrer has received an honorarium for a seminar at Genzyme. T Gasser has received consultancy fees from Cephalon and Merck-Serono, grants from Novartis, payments for lectures including service on speakers' bureaus from Boehringer Ingelheim, Merck-Serono, UCB, and Valean, and holds patents NGFN2 and KASPP. JA Hardy has received consulting fees or honoraria from Eisai and his institute has received consulting fees or honoraria from Merck-Serono. DM Maraganore has received extramural research funding support from the National Institutes of Health (2R01 ES10751), the Michael J. Fox Foundation (Linked Efforts to Accelerate Parkinson Solutions Award, Edmond J. Safra Global Genetics Consortia Award), and from Alnylam Pharmaceuticals and Medtronic (observational studies of Parkinson's disease). DM Maraganore has also received intramural research funding support from the Mayo Clinic and from NorthShore University Health System. DM Maraganore filed a provisional patent for a method to predict Parkinson's disease. This provisional patent is unlicensed. He also filed a provisional patent for a method to treat neurodegenerative disorders. That provisional patent has been licensed to Alnylam Pharmaceuticals and DM Maraganore has received royalty payments in total of less than $20,000. K Stefansson has received grants from deCODE. NR 34 TC 224 Z9 226 U1 7 U2 36 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAR PY 2012 VL 8 IS 3 AR e1002548 DI 10.1371/journal.pgen.1002548 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 918MV UT WOS:000302254800024 PM 22438815 ER PT J AU Wu, XY Shi, Z Cui, MX Han, M Ruvkun, G AF Wu, Xiaoyun Shi, Zhen Cui, Mingxue Han, Min Ruvkun, Gary TI Repression of Germline RNAi Pathways in Somatic Cells by Retinoblastoma Pathway Chromatin Complexes SO PLOS GENETICS LA English DT Article ID ELEGANS VULVAL DEVELOPMENT; C-ELEGANS; CAENORHABDITIS-ELEGANS; TRANSCRIPTIONAL REPRESSION; P GRANULES; LIN-35 RB; GENES ANTAGONIZE; PROTEIN; INTERFERENCE; EXPRESSION AB The retinoblastoma (Rb) tumor suppressor acts with a number of chromatin cofactors in a wide range of species to suppress cell proliferation. The Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called synMuv B genes, were identified in genetic screens for cell lineage defects caused by growth factor misexpression. Mutations in many synMuv B genes, including lin-35/Rb, also cause somatic misexpression of the germline RNA processing P granules and enhanced RNAi. We show here that multiple small RNA components, including a set of germline-specific Argonaute genes, are misexpressed in the soma of many synMuv B mutant animals, revealing one node for enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular architecture of their misexpressed P granules, their profile of misexpressed small RNA and P granule genes, as well as their enhancement of RNAi and the related silencing of transgenes. These differences define three classes of synMuv B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex, suggesting that intersecting chromatin pathways regulate the repression of small RNA and P granule genes in the soma and the potency of RNAi. Consistent with this, the DRM complex and the synMuv B heterochromatin complex were genetically additive and displayed distinct antagonistic interactions with the MES-4 histone methyltransferase and the MRG-1 chromodomain protein, two germline chromatin regulators required for the synMuv phenotype and the somatic misexpression of P granule components. Thus intersecting synMuv B chromatin pathways conspire with synMuv B suppressor chromatin factors to regulate the expression of small RNA pathway genes, which enables heightened RNAi response. Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene. C1 [Wu, Xiaoyun; Shi, Zhen; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Wu, Xiaoyun; Shi, Zhen; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Cui, Mingxue; Han, Min] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. [Cui, Mingxue; Han, Min] Univ Colorado, Howard Hughes Med Inst, Boulder, CO 80309 USA. RP Wu, XY (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu FU National Institutes of Health [AG16636, GM47869]; MGH FX This work was supported by the MGH Fund for Medical Discovery postdoctoral fellowship to XW and by grants from the National Institutes of Health (www.nih.gov) to GR (AG16636) and to MH (GM47869). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 76 TC 18 Z9 21 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD MAR PY 2012 VL 8 IS 3 AR e1002542 DI 10.1371/journal.pgen.1002542 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA 918MV UT WOS:000302254800019 PM 22412383 ER PT J AU Morabia, A Zhang, FF Kappil, MA Flory, J Mirer, FE Santella, RM Wolff, M Markowitz, SB AF Morabia, Alfredo Zhang, Fang Fang Kappil, Maya A. Flory, Janine Mirer, Frank E. Santella, Regina M. Wolff, Mary Markowitz, Steven B. TI Biologic and epigenetic impact of commuting to work by car or using public transportation: A case-control study SO PREVENTIVE MEDICINE LA English DT Article DE Transportation; Physical activity; Inflammation; Epigenetic ID C-REACTIVE PROTEIN; PARTICULATE AIR-POLLUTION; GENOMIC DNA METHYLATION; CANCER-FREE POPULATION; PHYSICAL-ACTIVITY; INFLAMMATORY MARKERS; ELDERLY SUBJECTS; BLOOD MARKERS; TRANSIT; OBESITY AB Background and aims. Commuting by public transportation (PT) entails more physical activity and energy expenditure than by cars, but its biologic consequences are unknown. Methods. In 2009-2010, we randomly sampled New York adults, usually commuting either by car (n =79) or PT (n = 101). Measures comprised diet and physical activity questionnaires, weight and height, white blood cell (WBC) count, C reactive protein, (CRP) gene-specific methylation (IL-6), and global genomic DNA methylation (LINE-1 methylation). Results. Compared to the 101 PT commuters, the 79 car drivers were about 9 years older, 2 kg/m(2) heavier, more often non-Hispanic whites, and ate more fruits and more meats. The 2005 guidelines for physical activity were met by more car drivers than PT users (78.5% vs. 65.0%). There were no differences in median levels of CRP (car vs. PT: 0.6 vs. 0.5 mg/dl), mean levels of WBC (car vs. PT: 6.7 vs. 6.5 cells/mm(3)), LINE-1 methylation (car vs. PT: 78.0% vs. 78.3%), and promoter methylation of IL-6 (car vs. PT: 56.1% vs. 58.0%). Conclusions. PT users were younger and lighter than car drivers, but their commute mode did not translate into a lower inflammatory response or a higher DNA methylation, maybe because, overall, car drivers were more physically active. (C) 2012 Elsevier Inc. All rights reserved. C1 [Morabia, Alfredo; Markowitz, Steven B.] CUNY, Queens Coll, Ctr Biol Nat Syst, Flushing, NY 11367 USA. [Morabia, Alfredo; Kappil, Maya A.; Santella, Regina M.] Columbia Univ, New York, NY USA. [Zhang, Fang Fang] Tufts Univ, Boston, MA 02111 USA. [Flory, Janine] James J Peters VA Med Ctr, Bronx, NY USA. [Mirer, Frank E.] CUNY, Hunter Coll, Flushing, NY 11367 USA. [Flory, Janine; Wolff, Mary] Mt Sinai Sch Med, New York, NY USA. RP Morabia, A (reprint author), CUNY, Queens Coll, Ctr Biol Nat Syst, 65-30 Kissena Blvd, Flushing, NY 11367 USA. EM alfredo.morabia@qc.cuny.edu OI , Maya/0000-0003-2913-2392 FU CUNY; NIEHS Center at Columbia University [1606]; University of North Texas Health Science Center School of Public Health FX This COMIR (Commuting Mode and Inflammatory Response) project received financial support from the CUNY Collaborative Incentive Research Grant (CIRG) program, round 16, number 1606, from the NIEHS Center ES009089 at Columbia University, and from the University of North Texas Health Science Center School of Public Health Seed Program. Results have been presented orally at the Meeting of the International Society for Environmental Epidemiology (ISEE, Barcelona, September 14, 2011). The authors thank Tashia Amstislavski and Steves Vanderpool for their help in the recruitment and data collection. NR 36 TC 7 Z9 7 U1 3 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR-APR PY 2012 VL 54 IS 3-4 BP 229 EP 233 DI 10.1016/j.ypmed.2012.01.019 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 923BL UT WOS:000302593000009 PM 22313796 ER PT J AU Weylandt, KH Chiu, CY Gomolka, B Waechter, SF Wiedenmann, B AF Weylandt, Karsten H. Chiu, Cheng-Ying Gomolka, Beate Waechter, Simon F. Wiedenmann, Bertram TI Omega-3 fatty acids and their lipid mediators: Towards an understanding of resolvin and protectin formation Omega-3 fatty acids and their resolvin/protectin mediators SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Review DE Omega-3; n-3 PUFA; Resolvins; Protectins; 17-HDHA; 18-HEPE ID N-3 FATTY-ACIDS; EPITHELIAL-CELL SURVIVAL; DAMPENS AIRWAY INFLAMMATION; CORONARY-HEART-DISEASE; FAT-1 TRANSGENIC MICE; DOCOSAHEXAENOIC ACID; NEUROPROTECTIN D1; ANTIINFLAMMATORY ACTIONS; OXIDATIVE STRESS; ELEVATED OMEGA-3-FATTY-ACIDS AB Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have long been associated with decreased inflammation and are also implicated in the prevention of tumorigenesis. Conventional thinking attributed this mainly to a suppressive effect of these fatty acids on the formation of arachidonic acid-derived prostaglandins and leukotrienes. Recent years have seen the discovery of a new class of inflammation-dampening and resolution-promoting n-3 PUFA-derived lipid mediators called resolvins and protectins. Chemically, these compounds are hydroxylated derivatives of the parent n-3 PUFA eicosapentaenoic acid (EPA) for the E-resolvins, and docosahexaenoic acid (DHA) for the D-resolvins and protectin D1. While a relatively large number of these compounds have been identified and characterized until now, with differences in the positions of the hydroxyl-groups as well as in the chirality at the different carbon atoms, all compounds share common precursor metabolites. 17-hydroperoxydocosahexaenoic acid (17-H(p)DHA) for the DNA-derived compounds and 18-hydroperoxyeicosapentaenoic acid (18-H(p)EPE) for the EPA-derived compounds. In this review we summarize the current knowledge about EPA- and DHA-derived resolvins and protectins and explore the potential use of the pro-resolvins 17-hydroxydocosahexaenoic acid (17-HDHA) and 18-hydroxyeicosapentaenoic acid (18-HEPE) as indicators of anti-inflammatory n-3 PUFA mediator formation. (C) 2012 Elsevier Inc. All rights reserved. C1 [Weylandt, Karsten H.; Chiu, Cheng-Ying; Gomolka, Beate; Waechter, Simon F.; Wiedenmann, Bertram] Charite, Rudolf Virchow Hosp, Dept Gastroenterol Hepatol & Endocrinol, D-13353 Berlin, Germany. [Weylandt, Karsten H.; Chiu, Cheng-Ying; Waechter, Simon F.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Weylandt, Karsten H.; Chiu, Cheng-Ying; Waechter, Simon F.] Harvard Univ, Sch Med, Boston, MA USA. RP Weylandt, KH (reprint author), Charite, Rudolf Virchow Hosp, Dept Gastroenterol Hepatol & Endocrinol, Augustenburger Pl 1, D-13353 Berlin, Germany. EM karsten.weylandt@charite.de FU German Research Council (DFG); German Society for Digestive and Metabolic Disease (DGVS) FX Ongoing work in KHW's lab is supported by the German Research Council (DFG), and KHW has also been the recipient of a Werner-Creutzfeldt Scholarship from the German Society for Digestive and Metabolic Disease (DGVS). The fat-1 mice were generously provided by Dr. Jing X. Kang at the Massachusetts General Hospital, Boston, and lipid mediator analysis was performed by Dr. Michael Rothe at Lipidomix, Berlin. NR 115 TC 94 Z9 99 U1 2 U2 37 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD MAR PY 2012 VL 97 IS 3-4 BP 73 EP 82 DI 10.1016/j.prostaglandins.2012.01.005 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 926SL UT WOS:000302851300001 PM 22326554 ER PT J AU Nath, SB Wong, YLI Marcus, SC Solomon, P AF Nath, Sara Bressi Wong, Yin-Ling Irene Marcus, Steven C. Solomon, Phyllis TI Predictors of Health Services Utilization among Persons with Psychiatric Disabilities Engaged in Supported Independent Housing SO PSYCHIATRIC REHABILITATION JOURNAL LA English DT Article DE health services utilization; psychiatric rehabilitation; case management; supported housing ID SERIOUS MENTAL-ILLNESS; MEDICAL-CARE; DISORDERS; SCHIZOPHRENIA; PEOPLE; ACCESS AB Objective: Persons with psychiatric disabilities are at greater risk for medical comorbidity, and prior research suggests these persons may underutilize health services. In response, this study examined the impact of engagement in psychiatric rehabilitation services, including case management, on utilization of general health services among persons with psychiatric disabilities engaged in supported housing, while controlling for demographic and clinical characteristics. Methods: Poisson regression analyses were used to examine the impact of socio-demographic, clinical, and service characteristics on reported utilization of general health services in the past year. Results: Findings indicated supported housing residents receiving case management coupled with weekly contact with residential support services visited a general health practitioner more frequently than those with less support services. Conclusions and Implications: Study results suggest psychiatric rehabilitation services provided to persons in the context of safe and affordable housing may represent an important mechanism for enabling persons with psychiatric disorders to access needed medical care. C1 [Wong, Yin-Ling Irene; Marcus, Steven C.; Solomon, Phyllis] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. [Marcus, Steven C.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Nath, SB (reprint author), Bryn Mawr Coll, Grad Sch Social Work & Social Res, 300 Airdale Rd, Bryn Mawr, PA 19010 USA. EM snath@brynmawr.edu FU NIMH NIH HHS [5-F31-MH67349] NR 46 TC 1 Z9 1 U1 5 U2 8 PU CENTER PSYCHIATRIC REHABILITATION PI BOSTON PA BOSTON UNIV, 930 COMMONWEALTH AVE, BOSTON, MA 02215 USA SN 1095-158X J9 PSYCHIATR REHABIL J JI Psychiatr. Rehabil. J. PD SPR PY 2012 VL 35 IS 4 BP 315 EP 323 DI 10.2975/35.4.2012.315.323 PG 9 WC Psychiatry; Rehabilitation SC Psychiatry; Rehabilitation GA 928GN UT WOS:000302971300005 PM 22491371 ER PT J AU Ch, AS Perez, C Silva, JR Ruiz-Tagle, A Mayol, R Munoz-Neira, C Nunez-Huasaf, J AF Slachevsky Ch, Andrea Perez J, Carolina Silva A, Jaime R. Ruiz-Tagle, Amparo Mayol, Rocio Munoz-Neira, Carlos Nunez-Huasaf, Javier TI Prognostic heterogeneity of attention deficit/hyperactivity disorder in adults SO REVISTA MEDICA DE CHILE LA Spanish DT Review DE Achievement; Adult; Deficit Disorder with Hyperactivity; Executive Function ID DEFICIT HYPERACTIVITY DISORDER; MENTAL TIME-TRAVEL; DUAL PATHWAY MODEL; EXECUTIVE FUNCTION; DELAY AVERSION; STRATEGY APPLICATION; LANGUAGE IMPAIRMENT; ADHD; GRATIFICATION; DYSFUNCTION AB Attention Deficit/Hyperactivity Disorder (ADHD) is a clinical syndrome characterized by an onset in early life. More than 65% of patients persist with manifestations of ADHD in adulthood. These symptoms may interfere in activities of daily-living, interpersonal relationships and professional and academic achievement. Nevertheless, the observation of an important group of adults with ADHD who do not show significant difficulties in the areas mentioned before puts into evidence the prognostic heterogeneity of this disorder. One of the current, most accepted explanations is the Double-Pathway Model: two double-dissociated deficits (Executive Disorders and Delayed-Reward Processing impairments) are involved in the genesis of ADHD, which explains the existence of different behavioral phenotypes. Moreover, personality traits like tenacity or perseverance are associated with higher levels of achievement in adults. On these grounds, we propose the hypothesis that the neurobiological correlate of tenacity/perseverance is a preserved Delayed-Reward Processing capacity, although further studies are needed to verify this idea. (Rev Med Chile 2012; 140: 379-385). C1 [Slachevsky Ch, Andrea] Univ Chile, Ctr Invest Avanzada Educ, Fac Med, Dept Farmacol,Inst Ciencias Biomed, Santiago, Chile. [Slachevsky Ch, Andrea] Univ Chile, Fac Med, Dept Ciencias Neurol, Santiago, Chile. [Slachevsky Ch, Andrea; Munoz-Neira, Carlos] Hosp Salvador, Serv Neurol, Unidad Neurol Cognit & Demencias, Santiago, Chile. [Slachevsky Ch, Andrea] Clin Alemana, Unidad Neurol, Alemana, Chile. [Nunez-Huasaf, Javier] Univ Chile, Fac Med, Hosp San Juan Dios, Santiago, Chile. [Nunez-Huasaf, Javier] Harvard Univ, Massachusetts Gen Hosp, Comp Sci Lab, Cambridge, MA 02138 USA. RP Ch, AS (reprint author), Univ Chile, Ctr Invest Avanzada Educ, Fac Med, Dept Farmacol,Inst Ciencias Biomed, Periodista Jose Carrasco Tapia N 75, Santiago, Chile. EM aslachevsky@me.com NR 55 TC 0 Z9 0 U1 1 U2 9 PU SOC MEDICA SANTIAGO PI SANTIAGO 9 PA BERNARDA MORIN 488 PROVIDENCIA, CASILLA 168 CORREO 55, SANTIAGO 9, 00000, CHILE SN 0034-9887 J9 REV MED CHILE JI Rev. Medica Chile PD MAR PY 2012 VL 140 IS 3 BP 379 EP 385 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 927RF UT WOS:000302927100016 ER PT J AU Fishman, JA Scobie, L Takeuchi, Y AF Fishman, Jay A. Scobie, Linda Takeuchi, Yasuhiro TI Xenotransplantation-associated infectious risk: a WHO consultation SO XENOTRANSPLANTATION LA English DT Article DE Clinical assays; clinical trials; donor; derived infection; infectious disease; porcine endogenous retrovirus; safety; xenotransplantation ID PORCINE ENDOGENOUS RETROVIRUS; PATHOGEN-FREE HERD; MINIATURE SWINE; TRANSMISSION CHARACTERISTICS; REPLICATION-COMPETENT; REVERSE-TRANSCRIPTASE; NEW-ZEALAND; NO EVIDENCE; PIG; IDENTIFICATION AB Xenotransplantation carries the potential risk of the transmission of infection with the cells or tissues of the graft. The degree of risk is unknown in the absence of clinical trials. The clinical application of xenotransplantation has important implications for infectious disease surveillance, both at the national and international levels. Preclinical data indicate that infectious disease events associated with clinical xenotransplantation from swine, should they occur, will be rare; data in human trials are limited but have demonstrated no transmission of porcine microorganisms including porcine endogenous retrovirus. Xenotransplantation will necessitate the development of surveillance programs to detect known infectious agents and, potentially, previously unknown or unexpected pathogens. The development of surveillance and safety programs for clinical trials in xenotransplantation is guided by a "Precautionary Principle," with the deployment of appropriate screening procedures and assays for source animals and xenograft recipients even in the absence of data suggesting infectious risk. All assays require training, standardization and validation, and sharing of laboratory methods and expertise to optimize the quality of the surveillance and diagnostic testing. Investigation of suspected xenogeneic infection events (xenosis, xenozoonosis) should be performed in collaboration with an expert data safety review panel and the appropriate public health and competent authorities. It should be considered an obligation of performance of xenotransplantation trials to report outcomes, including any infectious disease transmissions, in the scientific literature. Repositories of samples from source animals and from recipients prior to, and following xenograft transplantation are essential to the investigation of possible infectious disease events. Concerns over any potential hazards associated with xenotransplantation may overshadow potential benefits. Careful microbiological screening of source animals used as xenotransplant donors may enhance the safety of transplantation beyond that of allotransplant procedures. Xenogeneic tissues may be relatively resistant to infection by some human pathogens. Moreover, xenotransplantation may be made available at the time when patients require organ replacement on a clinical basis. Insights gained in studies of the microbiology and immunology of xenotransplantation will benefit transplant recipients in the future. This document summarizes approaches to disease surveillance in individual recipients of nonhuman tissues. C1 [Fishman, Jay A.] Massachusetts Gen Hosp, Transplantat Infect Dis & Compromised Host Progr, Boston, MA 02114 USA. [Fishman, Jay A.] Harvard Univ, Sch Med, Boston, MA USA. [Scobie, Linda] Glasgow Caledonian Univ, Sch Hlth & Life Sci, Glasgow G4 0BA, Lanark, Scotland. [Takeuchi, Yasuhiro] UCL, Wohl Virion Ctr, Div Infect & Immun, London, England. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplantat Infect Dis & Compromised Host Progr, Boston, MA 02114 USA. EM jfishman@partners.org FU NIAID [2010A056237, P01AI45897]; European Sixth Framework Programme (Life Science, Genomics and Biotechnology for Health) [LSHB-CT-2006-037377] FX This document was prepared to support discussions at the World Health Organization Second Global Consultation of Regulatory Requirements for Xenotransplantation Clinical Trials, Geneva, October 17-19, 2010. The authors are grateful for the expert editorial assistance of Luc Noel, Ralf Toenjes, Joachim Denner, Yannick Blanchard, Emanuele Cozzi, and Takaaki Kobayashi. JAF's research has been supported by NIAID 2010A056237 and P01AI45897. LS's and YT's research has been funded by the European Sixth Framework Programme (Life Science, Genomics and Biotechnology for Health) funded project XENOME, LSHB-CT-2006-037377. NR 51 TC 47 Z9 47 U1 2 U2 30 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAR-APR PY 2012 VL 19 IS 2 BP 72 EP 81 DI 10.1111/j.1399-3089.2012.00693.x PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 925XT UT WOS:000302796400002 PM 22497509 ER PT J AU Robinson, EB Koenen, KC McCormick, MC Munir, K Hallett, V Happe, F Plomin, R Ronald, A AF Robinson, Elise B. Koenen, Karestan C. McCormick, Marie C. Munir, Kerim Hallett, Victoria Happe, Francesca Plomin, Robert Ronald, Angelica TI A Multivariate Twin Study of Autistic Traits in 12-Year-Olds: Testing the Fractionable Autism Triad Hypothesis SO BEHAVIOR GENETICS LA English DT Article DE Autistic traits; Autism; Twins; Genetics; Genetic overlap ID PERVASIVE DEVELOPMENTAL DISORDERS; MULTIPLE-REGRESSION ANALYSIS; CAST CHILDHOOD ASPERGER; RARE DE-NOVO; GENERAL-POPULATION; SPECTRUM DISORDERS; ENVIRONMENTAL ETIOLOGIES; INDIVIDUAL-DIFFERENCES; GENETIC ETIOLOGY; SYMPTOM DOMAINS AB Autistic traits-social impairment, communication impairment, and restricted and repetitive behaviors and interests-are heritable in the general population. Previous analyses have consistently reported limited genetic and environmental overlap between autistic trait domains in samples assessed in middle childhood. Here we extend this research to parent-report data for 12-year-olds. Data from 5,944 pairs in the Twins Early Development Study were analyzed to explore the domain-specific heritability and degree of shared genetic and environmental influences across different autistic traits in the general population and among individuals scoring in the top 5% of each domain. Sex differences in the etiological estimates were also tested in these analyses. Autistic traits were moderately to highly heritable (0.58-0.88) at age 12. Bivariate genetic correlations in the full sample (0.18-0.40) and the extremes (0.24-0.67), as well as even lower unique environmental correlations, all suggested considerable fractionation of genetic and environmental influences across autistic trait domains, in line with previous findings. C1 [Robinson, Elise B.; Koenen, Karestan C.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02114 USA. [Robinson, Elise B.; Munir, Kerim] Harvard Univ, Sch Med, Mental Hlth & Dev Disabil MH DD Program, Div Dev Med,Childrens Hosp, Boston, MA 02114 USA. [Robinson, Elise B.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02115 USA. [Koenen, Karestan C.; McCormick, Marie C.] Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, Boston, MA 02114 USA. [Koenen, Karestan C.] Harvard Univ, Harvard Ctr Developing Child, Cambridge, MA 02138 USA. [Munir, Kerim] Harvard Univ, Sch Med, Dept Psychiat, Childrens Hosp, Boston, MA 02114 USA. [Hallett, Victoria; Happe, Francesca; Plomin, Robert; Ronald, Angelica] Kings Coll London, MRC Social Genet & Dev Psychiat Ctr, Inst Psychiat, London SE5 8AF, England. [Hallett, Victoria] Yale Univ, Yale Child Study Ctr, New Haven, CT 06520 USA. [Ronald, Angelica] Univ London, Ctr Brain & Cognit Dev, Dept Psychol Sci, London WC1E 7HX, England. RP Robinson, EB (reprint author), Harvard Univ, Dept Epidemiol, Sch Publ Hlth, 185 Cambridge St,6-236, Boston, MA 02114 USA. EM erobinso@hsph.harvard.edu RI Happe, Francesca/D-5544-2012; Ronald, Angelica/C-7812-2009; Koenen, Karestan/K-5402-2014; OI Ronald, Angelica/0000-0002-9576-2176; Robinson, Elise/0000-0003-2314-2792; McCormmick, Marie/0000-0002-3938-1707; Koenen, Karestan/0000-0003-3293-4281; Plomin, Robert/0000-0002-0756-3629; Happe, Francesca/0000-0001-9226-4000 FU MRC [G0500079]; National Institute of Mental Health/NIH at The Children's Hospital Boston, Harvard Medical School [MH71286]; Harvard School of Public Health [T32MH017119] FX The TEDS is funded by MRC grant G0500079 and has IRB approval. The research was specifically funded by a National Institute of Mental Health/NIH Research Fellowship in Mental Health and Developmental Disabilities (MH/DD) at The Children's Hospital Boston, Harvard Medical School (MH71286) and the Training Program in Psychiatric Genetics and Translational Research at the Harvard School of Public Health (T32MH017119). NR 51 TC 35 Z9 35 U1 5 U2 29 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD MAR PY 2012 VL 42 IS 2 BP 245 EP 255 DI 10.1007/s10519-011-9500-3 PG 11 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 924MX UT WOS:000302697100006 PM 21927971 ER PT J AU Srinivasan, VJ Radhakrishnan, H Lo, EH Mandeville, ET Jiang, JY Barry, S Cable, AE AF Srinivasan, Vivek J. Radhakrishnan, Harsha Lo, Eng H. Mandeville, Emiri T. Jiang, James Y. Barry, Scott Cable, Alex E. TI OCT methods for capillary velocimetry SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; DOPPLER TOMOGRAPHY; VELOCITY; MICROVASCULATURE; ANGIOGRAPHY; MICROSCOPY; SPECKLE; MODEL; BANDWIDTH AB To date, two main categories of OCT techniques have been described for imaging hemodynamics: Doppler OCT and OCT angiography. Doppler OCT can measure axial velocity profiles and flow in arteries and veins, while OCT angiography can determine vascular morphology, tone, and presence or absence of red blood cell (RBC) perfusion. However, neither method can quantify RBC velocity in capillaries, where RBC flow is typically transverse to the probe beam and single-file. Here, we describe new methods that potentially address these limitations. Firstly, we describe a complex-valued OCT signal in terms of a static scattering component, dynamic scattering component, and noise. Secondly, we propose that the time scale of random fluctuations in the dynamic scattering component are related to red blood cell velocity. Analysis was performed along the slow axis of repeated B-scans to parallelize measurements. We correlate our purported velocity measurements against two-photon microscopy measurements of RBC velocity, and investigate changes during hypercapnia. Finally, we image the ischemic stroke penumbra during distal middle cerebral artery occlusion (dMCAO), where OCT velocimetry methods provide additional insight that is not afforded by either Doppler OCT or OCT angiography. (c) 2012 Optical Society of America C1 [Srinivasan, Vivek J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Radhakrishnan, Harsha] Penn State Univ, Ctr Neural Engn, University Pk, PA 16802 USA. [Lo, Eng H.; Mandeville, Emiri T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol & Neurol, Charlestown, MA 02129 USA. [Jiang, James Y.; Barry, Scott; Cable, Alex E.] Thorlabs Inc, Adv Imaging Grp, Newton, NJ 07860 USA. RP Srinivasan, VJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, MGH MIT HMS Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM vjsriniv@nmr.mgh.harvard.edu RI Radhakrishnan, Harsha/K-5557-2012 FU National Institutes of Health [R00NS067050, NS055104, EB001954 R01]; American Heart Association [11IRG5440002]; Glaucoma Research Foundation Catalyst for a Cure 2 FX We acknowledge support from the National Institutes of Health (R00NS067050, NS055104, EB001954 R01), the American Heart Association (11IRG5440002), and the Glaucoma Research Foundation Catalyst for a Cure 2. We thank Maria Angela Franceschini for permission to use the OCT system. NR 41 TC 47 Z9 48 U1 0 U2 17 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD MAR 1 PY 2012 VL 3 IS 3 BP 612 EP 629 PG 18 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 925UK UT WOS:000302787000020 PM 22435106 ER PT J AU Auksorius, E Bromberg, Y Motiejunaite, R Pieretti, A Liu, L Coron, E Aranda, J Goldstein, AM Bouma, BE Kazlauskas, A Tearney, GJ AF Auksorius, Egidijus Bromberg, Yaron Motiejuenaite, Rueta Pieretti, Alberto Liu, Linbo Coron, Emmanuel Aranda, Jorge Goldstein, Allan M. Bouma, Brett E. Kazlauskas, Andrius Tearney, Guillermo J. TI Dual-modality fluorescence and full-field optical coherence microscopy for biomedical imaging applications SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID STRUCTURED ILLUMINATION; IN-VIVO; TOMOGRAPHY; LIGHT; ANGIOGENESIS; MOUSE; MODEL AB Full-field optical coherence microscopy (FFOCM) is a high-resolution interferometric technique that is particularly attractive for biomedical imaging. Here we show that combining it with structured illumination fluorescence microscopy on one platform can increase its versatility since it enables co-localized registration of optically sectioned reflectance and fluorescence images. To demonstrate the potential of this dual modality, a fixed and labeled mouse retina was imaged. Results showed that both techniques can provide complementary information and therefore the system could potentially be useful for biomedical imaging applications. (c) 2012 Optical Society of America C1 [Auksorius, Egidijus; Bromberg, Yaron; Liu, Linbo; Coron, Emmanuel; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Auksorius, Egidijus; Bromberg, Yaron; Liu, Linbo; Coron, Emmanuel; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Motiejuenaite, Rueta; Aranda, Jorge; Kazlauskas, Andrius] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Motiejuenaite, Rueta; Aranda, Jorge; Kazlauskas, Andrius] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Motiejuenaite, Rueta] Vilnius Univ, Dept Biochem & Biophys, Vilnius, Lithuania. [Pieretti, Alberto; Goldstein, Allan M.] Harvard Univ, Sch Med, Dept Pediat Surg, Boston, MA 02114 USA. [Pieretti, Alberto; Goldstein, Allan M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bouma, Brett E.; Tearney, Guillermo J.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Auksorius, E (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM auksorius.egidijus@mgh.harvard.edu RI Bromberg, Yaron/F-6570-2010; Coron, Emmanuel/K-2415-2015 OI Bromberg, Yaron/0000-0003-2565-7394; FU Air Force Office of Scientific Research [FA9550-10-1-0537]; NIH [R01HL076398, R01HL093717, R01CA103769, R01DK091923] FX We acknowledge financial support from the Air Force Office of Scientific Research under grant FA9550-10-1-0537 and the NIH under grants R01HL076398, R01HL093717, R01CA103769, R01DK091923. NR 23 TC 15 Z9 15 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD MAR 1 PY 2012 VL 3 IS 3 BP 661 EP 666 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 925UK UT WOS:000302787000024 PM 22435110 ER PT J AU Ballen, K AF Ballen, K. TI How to manage the transplant question in myelofibrosis SO BLOOD CANCER JOURNAL LA English DT Article DE transplantation; myelofibrosis; cord blood ID STEM-CELL TRANSPLANTATION; AGNOGENIC MYELOID METAPLASIA; CORD BLOOD TRANSPLANTATION; WORLD-HEALTH-ORGANIZATION; MARROW-TRANSPLANTATION; ESSENTIAL THROMBOCYTHEMIA; POLYCYTHEMIA-VERA; GRUPPO-ITALIANO; SCORING SYSTEM; MIDOLLO-OSSEO AB Allogeneic stem cell transplantation remains the only curative therapy for myelofibrosis. Despite advances in transplant, the morbidity and the mortality of the procedure necessitate careful patient selection. In this manuscript, we describe the new prognostic scoring system to help select appropriate patients for transplant and less aggressive therapies. We explore the advances in non-transplant therapy, such as with investigational agents. We review the blossoming literature on results of myeloablative, reduced intensity and alternative donor transplantation. Finally, we make recommendations for which patients are most likely to benefit from transplantation. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Ballen, K (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 0 Emerson,Suite 118, Boston, MA 02114 USA. EM kballen@partners.org NR 46 TC 12 Z9 12 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD MAR PY 2012 VL 2 AR e59 DI 10.1038/bcj.2012.3 PG 5 WC Oncology SC Oncology GA 925NT UT WOS:000302768700002 PM 22829254 ER PT J AU Ehrlich, S Walton, E Roffman, JL Weiss, D Puls, I Doehler, N Burghardt, R Lehmkuhl, U Hillemacher, T Muschler, M Frieling, H AF Ehrlich, Stefan Walton, Esther Roffman, Joshua L. Weiss, Deike Puls, Imke Doehler, Nico Burghardt, Roland Lehmkuhl, Ulrike Hillemacher, Thomas Muschler, Marc Frieling, Helge TI Smoking, But Not Malnutrition, Influences Promoter-Specific DNA Methylation of the Proopiomelanocortin Gene in Patients With and Without Anorexia Nervosa SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE proopiomelanocortin; DNA methylation; CpG island; smoking; malnutrition; anorexia nervosa ID MESSENGER-RNA EXPRESSION; CPG ISLAND METHYLATION; EATING-DISORDERS; MELANOCORTIN-4 RECEPTOR; EPIGENETIC REGULATION; ALCOHOL DEPENDENCE; BIPOLAR DISORDER; TOBACCO-SMOKING; DOWN-REGULATION; DIETARY-FOLATE AB Objective: Our pilot study evaluates the impact of environmental factors, such as nutrition and smoking status, on epigenetic patterns in a disease-associated gene. Method: We measured the effects of malnutrition and cigarette smoking on proopiomelanocortin (POMC) promoter-specific DNA methylation in female patients with and without anorexia nervosa (AN). POMC and its derived peptides (alpha melanocyte stimulating hormone and adrenocorticotropic hormone) are implicated in stress and feeding response. Promoter-specific DNA methylation of the POMC gene was determined in peripheral blood mononuclear cells of 54 healthy female control subjects, 40 underweight patients with AN, and 21 weight-restored patients with AN using bisulfite sequencing. Malnutrition was characterized by plasma leptin. Results: POMC promoter-specific DNA methylation was not affected by diagnosis or nutritional status but significantly negatively associated with cigarette smoking. Conclusions: Although malnutrition may be expected to reduce DNA methylation through its effects on one-carbon metabolism, our negative results are in line with several in vitro and clinical studies that did not show a direct relation between gene-specific DNA methylation and folate levels. In contrast, smoking has been repeatedly reported to alter DNA methylation of specific genes and should be controlled for in future epigenetic studies. C1 [Ehrlich, Stefan; Walton, Esther] Tech Univ Dresden, Dept Child & Adolescent Psychiat, Translat Dev Neurosci Sect, D-01307 Dresden, Germany. [Ehrlich, Stefan; Weiss, Deike; Doehler, Nico; Burghardt, Roland; Lehmkuhl, Ulrike] Charite, Dept Child & Adolescent Psychiat, D-13353 Berlin, Germany. [Ehrlich, Stefan; Roffman, Joshua L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Athinoula A Martinos Ctr Biomed Ima, Charlestown, MA USA. [Puls, Imke] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany. [Hillemacher, Thomas] Hannover Med Sch, Dept Psychiat Social Psychiat & Psychotherapy, Addict Res Ctr, Hannover, Germany. [Muschler, Marc; Frieling, Helge] Hannover Med Sch, Dept Psychiat Social Psychiat & Psychotherapy, Mol Neurosci Lab, Hannover, Germany. [Frieling, Helge] Univ Hosp Erlangen, Dept Psychiat & Psychotherapy, Erlangen, Germany. RP Ehrlich, S (reprint author), Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Child & Adolescent Psychiat, Fetscherstr 74, D-01307 Dresden, Germany. EM stefan@nmr.mgh.harvard.edu RI Hillemacher, Thomas/E-4596-2012; Frieling, Helge/C-5299-2015 OI Hillemacher, Thomas/0000-0002-3362-7868; Frieling, Helge/0000-0001-5146-9720 FU Charite-Universitatsmedizin Research Fund; German Research Fund (Deutsche Forschungsgemeinschaft) [EH 367/2-1]; Beyer Vital AG; Astra Zeneca Germany FX Funding for our study was provided by the Charite-Universitatsmedizin Research Fund and the German Research Fund (Deutsche Forschungsgemeinschaft; grant number EH 367/2-1). Dr Frieling holds grants from Beyer Vital AG and previously from Astra Zeneca Germany. Dr Frieling has consulted for Astra Zeneca, Merz, Otsuka, and Servier Germany. All authors have no conflict of interest. NR 74 TC 13 Z9 13 U1 0 U2 5 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD MAR PY 2012 VL 57 IS 3 BP 168 EP 176 PG 9 WC Psychiatry SC Psychiatry GA 925LC UT WOS:000302761700006 PM 22398003 ER PT J AU Larson, AM Pfeifer, HH Thiele, EA AF Larson, Anna M. Pfeifer, Heidi H. Thiele, Elizabeth A. TI Low glycemic index treatment for epilepsy in tuberous sclerosis complex SO EPILEPSY RESEARCH LA English DT Article DE Tuberous sclerosis complex; Epilepsy; Low glycemic index treatment; Ketogenic diet; mTOR pathway ID NATURAL-HISTORY; KETOGENIC DIET; EFFICACY AB Retrospective chart review of 15 patients with tuberous sclerosis complex (TSC) who initiated the low glycemic index treatment (LGIT) for epilepsy management at Massachusetts General Hospital over a five-year period. Prior to dietary therapy, this cohort (average age: 8.5 years) had tried an average of 5.8 anti-epileptic drugs with incomplete seizure control. At 6 months on the LGIT, 7/15 (47%) patients experienced >50% reduction in seizure frequency. (C) 2011 Elsevier B.V. All rights reserved. C1 [Larson, Anna M.; Pfeifer, Heidi H.; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Carol & James Herscot Ctr, Dept Neurol, Boston, MA 02114 USA. RP Thiele, EA (reprint author), Massachusetts Gen Hosp, Carol & James Herscot Ctr, Dept Neurol, Tuberous Sclerosis Complex,175 Cambridge St,Suite, Boston, MA 02114 USA. EM ethiele@partners.org FU Herscot Center for Tuberous Sclerosis Complex; Tuberous Sclerosis Alliance; NIH/NINDS [P01 NS024279] FX This study was supported by the Herscot Center for Tuberous Sclerosis Complex, the Tuberous Sclerosis Alliance, and NIH/NINDS P01 NS024279. NR 9 TC 13 Z9 16 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAR PY 2012 VL 99 IS 1-2 BP 180 EP 182 DI 10.1016/j.eplepsyres.2011.10.021 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 920TV UT WOS:000302431700024 PM 22119636 ER PT J AU Chen, CH Li, JS Hosseini, A Gadikota, HR Gill, TJ Li, GA AF Chen, Chih-Hui Li, Jing-Sheng Hosseini, Ali Gadikota, Hemanth R. Gill, Thomas J. Li, Guoan TI Anteroposterior stability of the knee during the stance phase of gait after anterior cruciate ligament deficiency SO GAIT & POSTURE LA English DT Article DE Anterior cruciate ligament; Gait; Kinematics ID FLUOROSCOPIC IMAGING TECHNIQUE; IN-SITU FORCES; ELECTROMYOGRAPHIC ANALYSIS; TIBIOFEMORAL KINEMATICS; MOTION ANALYSIS; JOINT MOTION; WALKING; VIVO; RECONSTRUCTION; OSTEOARTHRITIS AB Quadriceps avoidance and higher flexion strategies have been assumed as effects of ACL deficiency on knee joint function during gait. However, the effect of ACL deficiency on anteroposterior stability of the knee during gait is not well defined. In this study, 10 patients with unilateral acute ACL ruptures and the contralateral side intact performed gait on a treadmill. Flexion angles and anteroposterior translation of the ACL injured and the intact controlateral knees were measured at every 10% of the stance phase of the gait (from heel strike to toe-off) using a combined MRI and dual fluoroscopic imaging system (DFIS). The data indicated that during the stance phase of the gait, the ACL-deficient knees showed higher flexion angles compared to the intact contralateral side, consistent with the assumption of a higher flexion gait strategy. However, the data also :revealed that the ACL-deficient knees had higher anterior tibial translation compared to the intact contralateral side during the stance phase of the gait. The higher flexion gait strategy was not shown to correlate to a reduction of the anterior tibial translation in ACL deficient knees. These data may provide indications for conservative treatment or surgical reconstruction of the ACL injured knees in restoration of the knee kinematics during daily walking activities. (C) 2011 Elsevier B.V. All rights reserved. C1 [Chen, Chih-Hui; Li, Jing-Sheng; Hosseini, Ali; Gadikota, Hemanth R.; Gill, Thomas J.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Chen, Chih-Hui; Li, Jing-Sheng; Hosseini, Ali; Gadikota, Hemanth R.; Gill, Thomas J.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chen, Chih-Hui] Taichung Vet Gen Hosp, Dept Orthopaed Surg, Taichung, Taiwan. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU National Institute of Health [R01 AR055612]; Department of Orthopaedic Surgery at Massachusetts General Hospital FX The authors would like to gratefully acknowledge the financial support of the National Institute of Health (R01 AR055612) and the Department of Orthopaedic Surgery at Massachusetts General Hospital. NR 31 TC 24 Z9 25 U1 0 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD MAR PY 2012 VL 35 IS 3 BP 467 EP 471 DI 10.1016/j.gaitpost.2011.11.009 PG 5 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 921BO UT WOS:000302453200020 PM 22169387 ER PT J AU Cashman, EC Woo, SB AF Cashman, E. C. Woo, S. B. TI Clear cell carcinoma of the major salivary gland: time for a different approach to management? SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Letter C1 [Cashman, E. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Woo, S. B.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Cashman, EC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM emma_cashman@dfci.harvard.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD MAR PY 2012 VL 41 IS 3 BP 408 EP 409 DI 10.1016/j.ijom.2011.07.735 PG 2 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 921VL UT WOS:000302506100025 PM 21856122 ER PT J AU Hajrasouliha, AR Funaki, T Sadrai, Z Hattori, T Chauhan, SK Dana, R AF Hajrasouliha, Amir R. Funaki, Toshinari Sadrai, Zahra Hattori, Takaaki Chauhan, Sunil K. Dana, Reza TI Vascular Endothelial Growth Factor-C Promotes Alloimmunity by Amplifying Antigen-Presenting Cell Maturation and Lymphangiogenesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RISK CORNEAL TRANSPLANTATION; DRAINING LYMPH-NODES; FACTOR RECEPTOR-3; DENDRITIC CELLS; GRAFT-SURVIVAL; ANGIOGENESIS; VEGF; MICROENVIRONMENT; INFLAMMATION; BEVACIZUMAB AB PURPOSE. To investigate the role of anti-vascular endothelial growth factor (VEGF)-C therapy in corneal graft survival and concomitant suppression of hem-and lymph-angiogenesis. METHODS. Corneal suture model in BALB/c mice was placed and immunohistochemical staining was performed with CD31/PECAM-1 and LYVE-1 to quantify the level of blood and lymphatic vessels. Corneal transplants were done in BALB/c mice from C57BL/6 mice donors; grafts were subsequently scored for opacity. VEGF-C was blocked in the angiogenesis and transplant model using neutralizing monoclonal anti-VEGF-C (VGX-100) by intraperitoneal injection. To determine the function of VEGF-C in maturation of antigen-presenting cells (APCs), bone marrow-derived dendritic cells were generated and matured in the presence or absence of VEGF-C. RESULTS. VEGF-C expression was demonstrated to be markedly upregulated in corneal graft rejection. VEGF-C blockade, through administration of a VEGF-C blocking monoclonal antibody, suppresses corneal angiogenic responses, inhibits trafficking and maturation of APCs, and significantly improves allotransplant survival. CONCLUSIONS. These data suggest VEGF-C as a potentially important target in corneal transplant pharmacotherapy and immunobiology. (Invest Ophthalmol Vis Sci. 2012;53:1244-1250) DOI:10.1167/iovs.11-8668 C1 [Hajrasouliha, Amir R.; Funaki, Toshinari; Sadrai, Zahra; Hattori, Takaaki; Chauhan, Sunil K.; Dana, Reza] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. EM reza.dana@schepens.harvard.edu FU National Institutes of Health/National Eye Institute [EY-R01-12963]; Vegenics, Circadian Technologies Ltd. (Melbourne, Australia) FX Supported in part by National Institutes of Health/National Eye Institute Grant EY-R01-12963 (RD) and Vegenics, Circadian Technologies Ltd. (Melbourne, Australia). NR 39 TC 20 Z9 22 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2012 VL 53 IS 3 BP 1244 EP 1250 DI 10.1167/iovs.11-8668 PG 7 WC Ophthalmology SC Ophthalmology GA 925VT UT WOS:000302790700023 PM 22281820 ER PT J AU Yu, Y Reynolds, R Rosner, B Daly, MJ Seddon, JM AF Yu, Yi Reynolds, Robyn Rosner, Bernard Daly, Mark J. Seddon, Johanna M. TI Prospective Assessment of Genetic Effects on Progression to Different Stages of Age-Related Macular Degeneration Using Multistate Markov Models SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID COMPLEMENT FACTOR-H; RISK; VARIANT; SUSCEPTIBILITY; ASSOCIATION; DRUSEN; POLYMORPHISM; MACULOPATHY; LIPC; AMD AB PURPOSE. Understanding the effect of genes on progression to different stages of age-related macular degeneration (AMD) may suggest stage-specific therapeutic targets and more precise prediction of the development of this disease. METHODS. Progression events and time to each stage of AMD were derived from the longitudinal data of 2560 subjects without advanced AMD. SNPs in 12 AMD risk loci were genotyped. A multistate Markov model for progression from normal to intermediate drusen, then to large drusen, and eventually to neovascular disease (NV) or geographic atrophy (GA) was applied to estimate stage-specific hazard ratios for each SNP. The effects of these genetic factors were also estimated by a multivariate multistate Markov model adjusted for baseline age, sex, smoking, body mass index (BMI), education, antioxidant treatment, and the status of AMD in the fellow eye. RESULTS. Controlling for demographic and behavioral factors and other SNPs, the TT genotype of rs10468017 in LIPC was associated with decreased risk of progression from large drusen to NV (HR = 0.57, P = 0.04) and tended to reduce the risk of progression from normal to intermediate drusen (HR = 0.72, P = 0.07). The SNP rs1883025 (T allele) in ABCA1 was associated with decreased risk of progression from normal to intermediate drusen (HR per allele = 0.82 per allele, P = 9.7 x 10(-3)) and from intermediate drusen to large drusen (HR per allele = 0.77, P = 5.2 x 10(-3)). The genes CFH, C3, CFB, and ARMS2/HTRA1 were associated with progression from intermediate drusen to large drusen and from large drusen to GA or NV. CONCLUSIONS. Genes in different pathways influence progression to different stages of AMD. (Invest Ophthalmol Vis Sci. 2012;53:1548-1556) DOI:10.1167/iovs.11-8657 C1 [Yu, Yi; Reynolds, Robyn; Seddon, Johanna M.] Tufts Med Ctr, Dept Ophthalmol, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, Boston, MA 02111 USA. [Rosner, Bernard] Channing Labs, Boston, MA USA. [Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Daly, Mark J.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP Seddon, JM (reprint author), Tufts Med Ctr, Dept Ophthalmol, New England Eye Ctr, Ophthalm Epidemiol & Genet Serv, 800 Washington St,450, Boston, MA 02111 USA. EM jseddon@tuftsmedicalcenter.org FU National Institutes of Health, Bethesda, MD [R01-EY11309]; Massachusetts Lions Eye Research Fund, Inc.; Research to Prevent Blindness, Inc., New York, NY; American Macular Degeneration Foundation, Northampton, MA; Elizabeth O'Brien Trust; Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, MA; Virginia B. Smith Trust FX Supported by an anonymous donor (JMS) and in part by Grants R01-EY11309 from the National Institutes of Health, Bethesda, MD; Massachusetts Lions Eye Research Fund, Inc.; Unrestricted grant from Research to Prevent Blindness, Inc., New York, NY; the American Macular Degeneration Foundation, Northampton, MA; Elizabeth O'Brien Trust; Virginia B. Smith Trust; and the Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, MA. NR 35 TC 54 Z9 54 U1 3 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2012 VL 53 IS 3 BP 1548 EP 1556 DI 10.1167/iovs.11-8657 PG 9 WC Ophthalmology SC Ophthalmology GA 925VT UT WOS:000302790700063 PM 22247473 ER PT J AU Iyer, V Heller, V Armoundas, AA AF Iyer, Vivek Heller, Victoria Armoundas, Antonis A. TI Altered spatial calcium regulation enhances electrical heterogeneity in the failing canine left ventricle: implications for electrical instability SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE electrophysiological; molecular; EC coupling; calcium; remodeling; heart failure; arrhythmias ID INDUCED HEART-FAILURE; TRANSIENT OUTWARD CURRENT; ACTION-POTENTIAL CHARACTERISTICS; GUINEA-PIG HEARTS; TRANSMURAL HETEROGENEITY; REGIONAL DIFFERENCES; DILATED CARDIOMYOPATHY; ENDOCARDIAL MYOCYTES; RYANODINE RECEPTORS; NA+-CA2+ EXCHANGE AB Iyer V, Heller V, Armoundas AA. Altered spatial calcium regulation enhances electrical heterogeneity in the failing canine left ventricle: implications for electrical instability. J Appl Physiol 112: 944-955, 2012. First published December 22, 2011; doi: 10.1152/japplphysiol.00609.2011.-Myocytes across the left ventricular (LV) wall of the mammalian heart are known to exhibit heterogeneity of electrophysiological properties; however, the transmural variation of cellular electrophysiology and Ca2+ homeostasis in the failing LV is incompletely understood. We studied action potentials (APs), the L-type calcium (Ca2+) current (I-Ca,I-L), and intracellular Ca2+ transients ([Ca2+](i)) of subendocardial (Endo), midmyocardial (Mid), and subepicardial (Epi) tissue layers in the canine normal and tachycardia pacing-induced failing left ventricles. Heart failure (HF) was associated with significant prolongation of the AP duration in Mid myocytes. There were no differences in I-Ca,I-L density in normal Endo, Mid, and Epi myocytes, whereas in the failing heart, I-Ca,I-L density was downregulated by 45% and 26% (at +10 mV) in Endo and Mid myocytes, respectively. The rates of sarcoplasmic reticulum (SR) Ca2+ release and decay of the [Ca2+](i) were slowed, and the amplitude of the [Ca2+](i) was depressed in Endo and Epi myocytes isolated from failing, compared with normal, hearts. Experiments in sodium (Na+)-free solutions showed that Epi and Mid myocytes of the failing ventricle exhibit a greater reliance on the Na+-Ca2+ exchanger to remove cytosolic Ca2+ than myocytes isolated from normal hearts. Simulation studies in Endo, Mid, and Epi canine myocytes demonstrate the importance of L-type current density and SR Ca2+ uptake in modulating the potentially arrhythmogenic repolarization in HF. In conclusion, these results demonstrate that spatially heterogeneous decreases in I-Ca,I-L and defective cytosolic Ca2+ removal contribute to the altered [Ca2+](i) and AP profiles across the canine failing LV. These distinct electrophysiological features in myocytes from a failing heart contribute to a characteristic electrogram arising from increased dispersion of refractoriness across the LV, which may result in significant arrhythmogenic sequellae. C1 [Heller, Victoria; Armoundas, Antonis A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. [Iyer, Vivek] Columbia Univ, Dept Med, Div Cardiol, Med Ctr, New York, NY USA. [Heller, Victoria] Charite, Dept Cardiol & Pulmonol, D-13353 Berlin, Germany. RP Armoundas, AA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Boston, MA 02129 USA. EM aarmoundas@partners.org OI Stary, Victoria/0000-0002-3854-9934 FU American Heart Association [0365304U] FX Support for this work was provided by an American Heart Association Beginning Grant-in-Aid (#0365304U) to A. A. Armoundas. NR 60 TC 7 Z9 8 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2012 VL 112 IS 6 BP 944 EP 955 DI 10.1152/japplphysiol.00609.2011 PG 12 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 922GS UT WOS:000302535900003 PM 22194323 ER PT J AU Stuart-Andrews, CR Kelly, VJ Sands, SA Lewis, AJ Ellis, MJ Thompson, BR AF Stuart-Andrews, Christopher R. Kelly, Vanessa J. Sands, Scott A. Lewis, Angela J. Ellis, Matthew J. Thompson, Bruce R. TI Automated detection of the phase III slope during inert gas washout testing SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE inert gas washout; computer algorithm; alveolar slope ID VENTILATION HETEROGENEITY; SUSTAINED MICROGRAVITY; SULFUR-HEXAFLUORIDE; CYSTIC-FIBROSIS; SMALL AIRWAYS; LUNG-DISEASE; ASTHMA; INHOMOGENEITY; HELIUM; INFLAMMATION AB Stuart-Andrews CR, Kelly VJ, Sands SA, Lewis AJ, Ellis MJ, Thompson BR. Automated detection of the phase III slope during inert gas washout testing. J Appl Physiol 112: 1073-1081, 2012. First published December 15, 2011; doi:10.1152/japplphysiol.00372.2011.-We describe a method to determine the phase III slope for the purpose of calculating indexes of ventilation heterogeneity, S-acin and S-cond, from the multiple breath nitrogen washout test (MBNW). Our automated method applies a recursive, segmented linear regression technique to each breath of the MBNW test and determines the best point of transition, or breakpoint, between each phase of the washout. A sample set of 50 MBNW tests (controls, asthma, and COPD) was used to establish the conditions in which the phase III slope obtained from the automated technique best matched that obtained by two manual interpreters. We then applied our technique to a test set of 30 subjects (with an even number of subjects in each of the above groups) and compared these results against the manual analysis of a third independent manual interpreter. Indexes of ventilation heterogeneity were determined using both methods and compared. The phase III slopes determined by the automatic technique best matched the manual interpreter when the phase III slope was calculated from the phase II-III transition point plus the addition of 50% of the phase II volume to the end of the expiration. Calculation of the indexes S-acin and S-cond showed no overall difference between analysis methods in either S-acin (P = 0.14) or S-cond (P = 0.59) when the set threshold was applied to our automated analysis. Our analysis method provides an alternate means for rapid quantification of the MBNW test, removing operator dependence without alteration in either S-acin or S-cond. C1 [Stuart-Andrews, Christopher R.; Kelly, Vanessa J.; Lewis, Angela J.; Ellis, Matthew J.; Thompson, Bruce R.] Alfred Hosp, Dept Allergy Immunol & Resp Med, Serv Physiol, Melbourne, Vic, Australia. [Kelly, Vanessa J.; Thompson, Bruce R.] Monash Univ, Dept Med Nursing & Hlth Sci, Clayton, Vic, Australia. [Kelly, Vanessa J.; Thompson, Bruce R.] Cooperat Res Council Asthma & Airways, Glebe, NSW, Australia. [Kelly, Vanessa J.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Kelly, Vanessa J.; Sands, Scott A.] Harvard Univ, Sch Med, Boston, MA USA. [Sands, Scott A.] Monash Univ, Ritchie Ctr Baby Hlth Res, Monash Inst Med Res, Clayton, Vic, Australia. [Sands, Scott A.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. RP Stuart-Andrews, CR (reprint author), Alfred Hosp, Dept Allergy Immunol & Resp Med, Serv Physiol, Melbourne, Vic, Australia. EM C.Stuart-Andrews@alfred.org.au OI Thompson, Bruce/0000-0002-5885-0652 FU National Health and Medical Research Council of Australia [521808, 486101, 491103]; Cooperative Research Centre for Asthma and Airways (CRCAA); American Australian Association; American Heart Association FX Financial support was provided to V. J. Kelly by research grants from the National Health and Medical Research Council of Australia (Grant 521808), the Cooperative Research Centre for Asthma and Airways (CRCAA), and the American Australian Association. S. A. Sands received support from an American Heart Association Post-Doctoral Fellowship. B. R. Thompson also received financial support through the National Health and Medical Research Council of Australia (Grants 486101 and 491103). NR 31 TC 16 Z9 16 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2012 VL 112 IS 6 BP 1073 EP 1081 DI 10.1152/japplphysiol.00372.2011 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 922GS UT WOS:000302535900019 PM 22174406 ER PT J AU Zwemer, EK Mahler, HIM Werchniak, AE Recklitis, CJ AF Zwemer, Eric K. Mahler, Heike I. M. Werchniak, Andrew E. Recklitis, Christopher J. TI Sun exposure in young adult cancer survivors on and off the beach: results from Project REACH SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Cancer survivors; Sun protection behaviors; Incidental exposure; Radiation therapy ID HEMATOPOIETIC-CELL TRANSPLANTATION; APPEARANCE-BASED INTERVENTIONS; BEHAVIORAL RISK-FACTORS; SKIN-CANCER; CHILDHOOD-CANCER; PROTECTION BEHAVIORS; BASAL-CELL; UNIVERSITY-STUDENTS; IONIZING-RADIATION; ADOLESCENT CANCER AB Background Although cancer survivors are at risk for future skin cancers, many do not practice recommended sun protection. Studies have demonstrated poor adherence to specific behaviors (e.g., sunscreen, artificial tanning) during sunbathing, but less is known about survivors' typical amount of sun exposure during activities other than sunbathing. Methods We conducted a mailed survey of 153 adults (median age=26.1) diagnosed with a non-skin cancer before age 30. Information on recent sunbathing and incidental sun exposures, protective behaviors, and perceived vulnerability was collected. Analyses focused on characterizing survivors with the lowest levels of recommended sun protection. Results Twenty-nine percent of participants exhibited low sun protection adherence during sunbathing and 31% during incidental exposure. Younger age was associated with low adherence, but this difference was significant only for sunbathing (OR=0.4; 95% CI, 0.2-0.9). Women were more likely than men to have low adherence during sunbathing (34.0% vs. 20.3%; OR=2.44; 95% CI, 1.1-5.5). Survivors treated with radiation did not differ on exposures, adherence, or perceived vulnerability to the sun, despite feeling more susceptible to skin cancers (p=0.03). Conclusions Despite known skin cancer risks, many young cancer survivors receive significant sun exposure. Assessment of sunbathing alone fails to capture sun exposure behaviors, particularly in men. Survivors treated with radiation may recognize their increased risk of skin cancer, but not the role of sun protection in modifying that risk. C1 [Zwemer, Eric K.; Recklitis, Christopher J.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Perini Family Survivors Ctr, Boston, MA 02215 USA. [Werchniak, Andrew E.] Harvard Univ, Dana Farber Canc Inst, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. [Mahler, Heike I. M.] Univ Calif, Dept Psychol, La Jolla, CA USA. RP Recklitis, CJ (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Perini Family Survivors Ctr, 450 Brookline Ave,DFCI D321, Boston, MA 02215 USA. EM Christopher_Recklitis@dfci.harvard.edu NR 50 TC 5 Z9 5 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD MAR PY 2012 VL 6 IS 1 BP 63 EP 71 DI 10.1007/s11764-011-0201-y PG 9 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA 920PS UT WOS:000302419400008 PM 22002547 ER PT J AU Burstein, HJ Griggs, JJ AF Burstein, Harold J. Griggs, Jennifer J. TI Deep Time: The Long and the Short of Adjuvant Endocrine Therapy for Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; LETROZOLE; TRIAL; RECURRENCE; SEQUENCE; RELAPSE C1 [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Griggs, Jennifer J.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 18 TC 9 Z9 9 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2012 VL 30 IS 7 BP 684 EP 686 DI 10.1200/JCO.2011.40.1455 PG 4 WC Oncology SC Oncology GA 923NG UT WOS:000302625400006 PM 22271478 ER PT J AU Meropol, NJ Kris, MG Winer, EP AF Meropol, Neal J. Kris, Mark G. Winer, Eric P. TI The American Society of Clinical Oncology's Blueprint for Transforming Clinical and Translational Cancer Research SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 [Meropol, Neal J.] Case Western Reserve Univ, Case Comprehens Canc Ctr, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Kris, Mark G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Meropol, NJ (reprint author), Case Western Reserve Univ, Case Comprehens Canc Ctr, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. OI Kris, Mark/0000-0002-7317-5341 NR 1 TC 9 Z9 10 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2012 VL 30 IS 7 BP 690 EP 691 DI 10.1200/JCO.2011.40.1125 PG 2 WC Oncology SC Oncology GA 923NG UT WOS:000302625400008 PM 22215747 ER PT J AU Jin, H Tu, DS Zhao, NQ Shepherd, LE Goss, PE AF Jin, Huan Tu, Dongsheng Zhao, Naiqing Shepherd, Lois E. Goss, Paul E. TI Longer-Term Outcomes of Letrozole Versus Placebo After 5 Years of Tamoxifen in the NCIC CTG MA.17 Trial: Analyses Adjusting for Treatment Crossover SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EXTENDED ADJUVANT THERAPY; STAGE BREAST-CANCER; RANDOMIZED-TRIAL; CLINICAL-TRIAL; WOMEN; INFERENCE AB Purpose The interim analysis of the National Cancer Institute of Canada Clinical Trials Group MA. 17 trial showed that letrozole was significantly better than placebo in disease-free survival (DFS) for postmenopausal women with hormone receptor-positive breast cancer following about 5 years of tamoxifen therapy. When patients were unblinded, those on placebo were offered letrozole. Longer-term efficacy of letrozole, especially survival, was of particular interest because the median follow-up of the first interim analysis was only 2.5 years. Efficacy was difficult to assess because more than 60% of placebo patients crossed over to letrozole after being unblinded. Patients and Methods Two statistical approaches were used to adjust for the potential effects of treatment crossover: one was based on the inverse probability of censoring weighted (IPCW) Cox model and the other on a Cox model with time-dependent covariates. Results With a median follow-up of 64 months, the hazard ratios (HRs) of letrozole and placebo from the IPCW analyses were HR of 0.52 (95% CI, 0.45 to 0.61; P < .001) for DFS, HR of 0.51 (95% CI, 0.42 to 0.61; P < .001) for distant disease-free survival (DDFS), and HR of 0.61 (95% CI, 0.52 to 0.71; P , .001) for overall survival (OS). The results from the analyses based on the Cox model with time-dependent covariates were similar for letrozole and placebo: HR of 0.58 (95% CI, 0.47 to 0.72; P < .001) for DFS, HR of 0.68 (95% CI, 0.52 to 0.88; P = .004) for DDFS, and HR of 0.76 (95% CI, 0.60 to 0.96; P = .02) for OS. Conclusion Exploratory analyses based on longer follow-up and adjusting for treatment crossover suggest that extended adjuvant letrozole was superior to placebo in DFS, DDFS, and OS. J Clin Oncol 30:718-721. (C) 2011 by American Society of Clinical Oncology C1 [Tu, Dongsheng] Queens Univ, Canc Res Inst, NCIC Clin Trials Grp, Kingston, ON K7L 3N6, Canada. [Jin, Huan; Zhao, Naiqing] Fudan Univ, Sch Publ Hlth, Shanghai 200433, Peoples R China. [Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Tu, DS (reprint author), Queens Univ, Canc Res Inst, NCIC Clin Trials Grp, 10 Stuart St, Kingston, ON K7L 3N6, Canada. EM dtu@ctg.queensu.ca FU Naiqing Zhao; Bayer Pharmaceuticals; Novartis FX Naiqing Zhao, Bayer Pharmaceuticals, Novartis NR 13 TC 60 Z9 63 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2012 VL 30 IS 7 BP 718 EP 721 DI 10.1200/JCO.2010.34.4010 PG 4 WC Oncology SC Oncology GA 923NG UT WOS:000302625400013 PM 22042967 ER PT J AU Gildengers, A Tatsuoka, C Bialko, C Cassidy, KA Al Jurdi, RK Gyulai, L Mulsant, BH Young, RC Sajatovic, M AF Gildengers, Ariel Tatsuoka, Curtis Bialko, Christopher Cassidy, Kristin A. Al Jurdi, Rayan K. Gyulai, Laszlo Mulsant, Benoit H. Young, Robert C. Sajatovic, Martha TI Correlates of Treatment Response in Depressed Older Adults With Bipolar Disorder SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE bipolar disorder; elderly; geriatric; lamotrigine; mood stabilizer; anticonvulsant; depression ID WEEKLY SYMPTOMATIC STATUS; RATING-SCALE; II DISORDER; ANTIDEPRESSANT-TREATMENT; SUICIDAL-BEHAVIOR; NATURAL-HISTORY; TRIAL; LIFE; PREVENTION; PLASTICITY AB Aims: To identify baseline clinical factors associated with acute treatment response in depressed older adults with bipolar disorder (BD) receiving lamotrigine. Methods: Secondary analysis of a multisite, 12-week, open-label, uncontrolled study of add-on lamotrigine in 57 adults 60 years and older with BD I or II depression. Measures included the Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). Cardiometabolic risk was measured with total serum cholesterol and the Cumulative Illness Rating Scale-Geriatric (CIRS-G) item # 13 (endocrine/metabolic burden). Neurocognitive (executive) function was evaluated using the Trail Making Test. Results: Greater reduction in MADRS from baseline was associated with higher baseline cardiometabolic burden at 6 and 9 weeks and lower YMRS scores at 9 weeks. At 12 weeks, improvement in the MADRS from baseline was no longer significantly related to baseline cardiometabolic burden or YMRS scores. A longitudinal mixed model of MADRS scores corroborated these findings with a significant finding of time-by-baseline cholesterol level interaction. In a subset of participants, better baseline executive function was related to greater improvement in the MADRS at 9 weeks but not at 6 or 12 weeks. Among all participants, higher baseline YMRS scores were related to greater likelihood of dropout. Conclusions: Lamotrigine appears to work best in depressed elderly patients with BD who have high cardiometabolic risk and low level of mania. Agents like lamotrigine that act primarily on neuroprogressive pathways involving oxidative stress, neurotrophins, and inflammation may be particularly effective in individuals with BD who have significant cardiometabolic burden because of their effects on shared vulnerability factors in BD and medical illness. C1 [Gildengers, Ariel] Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Tatsuoka, Curtis] Case Western Reserve Univ, Sch Med, Dept Neurol, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Bialko, Christopher; Cassidy, Kristin A.; Sajatovic, Martha] Case Western Reserve Univ, Sch Med, Dept Psychiat, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Al Jurdi, Rayan K.] Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. [Gyulai, Laszlo] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Gyulai, Laszlo] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Mulsant, Benoit H.] Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Young, Robert C.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. RP Gildengers, A (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM gildengersag@upmc.edu RI Sajatovic, Martha/I-8001-2014; OI Young, Robert/0000-0002-6380-6314 FU GlaxoSmithKline, Research Triangle Park, North Carolina, USA; Case Western Reserve University [UL1RR024989]; GlaxoSmithKline; Canadian Institutes of Health Research; NIH; Bristol-Myers Squibb; Wyeth; AstraZeneca; Janssen; Pfizer; Merck; Ortho-McNeil Janssen FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by an investigator-initiated research grant from GlaxoSmithKline, Research Triangle Park, North Carolina, USA, and grant UL1RR024989 from Case Western Reserve University Clinical and Translational Science Awards (CTSA). The CTSA is a component of the National Institute of Health (NIH) and NIH Roadmap for Medical Research. The contents are solely the responsibility of the authors and do not necessarily represent the official view of the National Center for Research Resources or the NIH. Ariel Gildengers, Rayan K. Al-Jurdi, Laszlo Gyulai, and Robert C. Young received funding for research from GlaxoSmithKline to conduct this investigator-initiated study. Benoit H. Mulsant has received funding for research from GlaxoSmithKline, the Canadian Institutes of Health Research, NIH, Bristol-Myers Squibb, and Wyeth. Robert C. Young has received funding for research from NIH, GlaxoSmithKline, AstraZeneca, and Janssen. Martha Sajatovic received research grants from AstraZeneca, Pfizer, Merck, and Ortho-McNeil Janssen; is a consultant for Cognition Group and United BioSource Corporation (Bracket); and receives royalties from Springer Press, Johns Hopkins University Press, and Oxford Press. All other authors have no conflicts to report. NR 42 TC 3 Z9 3 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD MAR PY 2012 VL 25 IS 1 SI SI BP 37 EP 42 DI 10.1177/0891988712436685 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 923NM UT WOS:000302626000007 PM 22467845 ER PT J AU Fox, E Patel, S Wathen, JK Schuetze, S Chawla, S Harmon, D Reinke, D Chugh, R Benjamin, RS Helman, LJ AF Fox, Elizabeth Patel, Shreyaskumar Wathen, J. Kyle Schuetze, Scott Chawla, Sant Harmon, David Reinke, Denise Chugh, Rashmi Benjamin, Robert S. Helman, Lee J. TI Phase II Study of Sequential Gemcitabine Followed by Docetaxel for Recurrent Ewing Sarcoma, Osteosarcoma, or Unresectable or Locally Recurrent Chondrosarcoma: Results of Sarcoma Alliance for Research Through Collaboration Study 003 SO ONCOLOGIST LA English DT Article C1 [Fox, Elizabeth] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Patel, Shreyaskumar; Wathen, J. Kyle; Benjamin, Robert S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Schuetze, Scott; Reinke, Denise; Chugh, Rashmi] Univ Michigan, Ann Arbor, MI 48109 USA. [Chawla, Sant] Sarcoma Oncol Ctr, Los Angeles, CA USA. [Harmon, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fox, Elizabeth; Helman, Lee J.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Fox, E (reprint author), Childrens Hosp Philadelphia, Div Oncol, Civ Ctr Blvd,CTRB 4016, Philadelphia, PA 19104 USA. EM foxe@email.chop.edu NR 0 TC 31 Z9 34 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAR PY 2012 VL 17 IS 3 BP 321 EP 321 DI 10.1634/theoncologist.2010-0265 PG 1 WC Oncology SC Oncology GA 919YQ UT WOS:000302368500004 PM 22363068 ER PT J AU Delate, T Witt, DM Ritzwoller, D Weeks, JC Kushi, L Hornbrook, MC Bowles, EJA Schrag, D AF Delate, Thomas Witt, Daniel M. Ritzwoller, Debra Weeks, Jane C. Kushi, Lawrence Hornbrook, Mark C. Bowles, Erin J. Aiello Schrag, Deborah TI Outpatient Use of Low Molecular Weight Heparin Monotherapy for First-Line Treatment of Venous Thromboembolism in Advanced Cancer SO ONCOLOGIST LA English DT Article DE Venous thromboembolism; Anticoagulants; Neoplasms; Ambulatory care ID ANTITHROMBOTIC THERAPY; PALLIATIVE CARE; THROMBOSIS; PROPHYLAXIS; DISEASE; RISK AB Background. Evidence-based treatment guidelines recommend low molecular weight heparin (LMWH) mono-therapy for cancer-associated venous thromboembolism (VTE). This analysis assessed the first-line treatment strategies for VTE in patients with advanced solid tumors. Methods. Using administrative data from advanced lung, prostate, colon, or breast cancer patients diagnosed between January 2000 and December 2007 at four HMOs with integrated delivery systems, patients with an inpatient or outpatient VTE diagnosed within 2 years after cancer diagnosis and an outpatient purchase of warfarin, LMWH, and/or fondaparinux anticoagulant within 7 days of the VTE diagnosis were identified. First-line outpatient VTE pharmacological treatment and factors independently associated with receipt/non-receipt of LMWH monotherapy were assessed. Results. Overall, 25% of the 1,089 eligible patients received LMWH monotherapy as primary VTE treatment. The percentage increased steadily over time from 18% among patients diagnosed in 2000 to 31% among those diagnosed in 2007. Factors associated with LMWH monotherapy included VTE diagnosis year, chemotherapy within 60 days prior to VTE diagnosis, history of VTE prior to cancer diagnosis, and invasive surgery in the 90 days following VTE diagnosis. Colorectal and prostate cancer patients versus lung cancer patients and stage III versus stage IV patients were less likely to be treated with LMWH monotherapy. Conclusions. Adoption of LMWH monotherapy as initial treatment for cancer-associated VTE was low but increased steadily over the study period. Future studies should explore reasons underlying the underutilization of this preferred evidence-based treatment as well as the comparative effectiveness of LMWH versus warfarin-based anticoagulation in real-world cancer patients with VTE. The Oncologist 2012; 17: 419-427 C1 [Delate, Thomas] Kaiser Permanente Colorado, Dept Pharm, Clin Pharm Res, Aurora, CO 80011 USA. [Ritzwoller, Debra] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Weeks, Jane C.; Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kushi, Lawrence] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Hornbrook, Mark C.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Bowles, Erin J. Aiello] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. RP Delate, T (reprint author), Kaiser Permanente Colorado, Dept Pharm, Clin Pharm Res, 16601 E Centretech Pkwy, Aurora, CO 80011 USA. EM tom.delate@kp.org RI Inov Farmaceutica, Inct/K-2313-2013; OI Kushi, Lawrence/0000-0001-9136-1175 FU National Cancer Institute [NCI 5U19CA079689, U19CA79689] FX This study was supported by National Cancer Institute grants NCI 5U19CA079689 (D. R. and J.C.W., MPIs) and U19CA79689 (Wagner, PI). We acknowledge the contributions of Stephanie Latimer and Addie Clark in developing the SAS code to extract the necessary data elements from each site's VDW. NR 28 TC 14 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 J9 ONCOLOGIST JI Oncologist PD MAR PY 2012 VL 17 IS 3 BP 419 EP 427 DI 10.1634/theoncologist.2011-0323 PG 9 WC Oncology SC Oncology GA 919YQ UT WOS:000302368500016 PM 22334451 ER PT J AU Price, EL Bereknyei, S Kuby, A Levinson, W Braddock, CH AF Price, Erika Leemann Bereknyei, Sylvia Kuby, Alma Levinson, Wendy Braddock, Clarence Henry, III TI New elements for informed decision making: A qualitative study of older adults' views SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Informed decision making; Shared decision making; New elements for informed decision making; Qualitative analysis; Focus groups; Older adults ID HEALTH-CARE; PATIENTS PREFERENCES; PATIENT INVOLVEMENT; CLINICAL DECISIONS; MEDICAL ENCOUNTER; PARTICIPATION; PHYSICIANS; TIME; COMMUNICATION; PERCEPTIONS AB Objective: To explore older adults' views of existing informed decision making (IDM) elements and investigate the need for additional elements. Methods: We recruited persons 65 and older to participate in six focus groups. Participants completed questionnaires about IDM preferences, and discussed videotapes of idealized patient-physician interactions in light of seven IDM elements: (1) discussion of the patient's role in decision making; (2) discussion of the clinical issue; (3) discussion of alternatives; (4) discussion of benefits/risks; (5) discussion of uncertainties; (6) assessment of patient understanding; and (7) exploration of patient preference. We used a modified grounded theory approach to assess agreement with existing IDM elements and identify new elements. Results: In questionnaires, 97-100% of 59 participants rated each IDM element as "somewhat" or "very" important. Qualitative analysis supported existing elements and suggested two more: opportunity for input from trusted others, and discussion of decisions' impacts on patients' daily lives. Elements overlapped with global communication themes. Conclusion: Focus groups affirmed existing IDM elements and suggested two more with particular relevance for older patients. Practice implications: Incorporation of additional IDM elements into clinical practice can enhance informed participation of older adults in decision making. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Price, Erika Leemann] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Price, Erika Leemann] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Bereknyei, Sylvia; Braddock, Clarence Henry, III] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Kuby, Alma] Univ Chicago, Natl Opin Res Ctr, Chicago, IL 60637 USA. [Levinson, Wendy] Univ Toronto, Dept Med, Toronto, ON, Canada. RP Price, EL (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box VAMC-111, San Francisco, CA 94121 USA. EM erika.price@ucsf.edu OI Bereknyei Merrell, Sylvia /0000-0002-5525-0379 FU National Institute on Aging, National Institutes of Health [R01 AG18781-02] FX This study was supported by grant no. R01 AG18781-02 from the National Institute on Aging, National Institutes of Health. We would like to thank the National Opinion Research Center and focus group participants for their contributions. NR 37 TC 18 Z9 18 U1 0 U2 4 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 MAR PY 2012 VL 86 IS 3 BP 335 EP 341 DI 10.1016/j.pec.2011.06.006 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 924EA UT WOS:000302672700010 PM 21757315 ER PT J AU Peters, JM Madhavan, VL Kazacos, KR Husson, RN Dangoudoubiyam, S Soul, JS AF Peters, Jurriaan M. Madhavan, Vandana L. Kazacos, Kevin R. Husson, Robert N. Dangoudoubiyam, Sriveny Soul, Janet S. TI Good Outcome With Early Empiric Treatment of Neural Larva Migrans Due to Baylisascaris procyonis SO PEDIATRICS LA English DT Article DE raccoon; Baylisascaris; larva migrans; meningoencephalitis; encephalomyelitis ID EOSINOPHILIC MENINGITIS; ENCEPHALITIS; DISEASE; MENINGOENCEPHALITIS; TOXOCARIASIS; NEMATODIASIS; CHILDREN; MRI AB We report a remarkably good outcome in a 14-month-old boy with early clinical diagnosis and aggressive empirical treatment of neural larva migrans caused by the raccoon roundworm Baylisascaris procyonis. He presented with fever, meningismus, lethargy, irritability and asymmetric spastic extremity weakness. Early findings of marked blood and cerebrospinal fluid eosinophilia and of diffuse white matter signal abnormality in the brain and spinal cord on MRI suggested a parasitic encephalomyelitis. Rapid presumptive treatment with albendazole and high-dose steroids halted progression of clinical signs. The diagnosis was confirmed by 2 sequential enzyme-linked immunosorbent assay studies positive for B procyonis serum immunoglobulin G and by Western blot. Field examination with soil sampling yielded infective Baylisascaris eggs. Repeat MRI 3 months later showed atrophy and diffuse, chronic white matter abnormalities, discordant with the marked clinical improvement in this interval. At 10 months, residual neurologic deficits included subtle paraparesis and moderate language delay. This case is the first in which spinal involvement in human Baylisascaris infection was clinically suspected and confirmed by neuroimaging. Importantly, early diagnosis and aggressive treatment of Baylisascaris meningo-encephalitis and myelitis with albendazole and high-dose steroids likely contributed to the good outcome in this patient, in contrast with previous reports. Pediatrics 2012; 129:e806-e811 C1 [Peters, Jurriaan M.; Soul, Janet S.] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Husson, Robert N.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Madhavan, Vandana L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Infect Dis Unit, Boston, MA USA. [Kazacos, Kevin R.; Dangoudoubiyam, Sriveny] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. RP Soul, JS (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. EM janet.soul@childrens.harvard.edu OI Peters, Jurriaan/0000-0002-6725-2814 NR 30 TC 4 Z9 6 U1 1 U2 12 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 2012 VL 129 IS 3 BP E806 EP E811 DI 10.1542/peds.2011-2078 PG 6 WC Pediatrics SC Pediatrics GA 922IQ UT WOS:000302541000029 PM 22311989 ER PT J AU Essig, M Dinkel, J Zamecnik, C AF Essig, M. Dinkel, J. Zamecnik, C. TI Visualization of radiation effects on the central nervous system SO RADIOLOGE LA German DT Article DE Morbidity; Tumor patients; Magnetic resonance imaging (MRI); Morphological imaging correlates; Survival time extension ID INDUCED CAVERNOUS HEMANGIOMAS; CHEMOTHERAPY; THERAPY; BRAIN; METHOTREXATE; LEUKOENCEPHALOPATHY; ENCEPHALOPATHY; SPECTROSCOPY; IRRADIATION; LYMPHOMA AB Therapy-related side effects, which are detectable with magnetic resonance imaging (MRI) at high sensitivity, are one of the most frequent causes of morbidity in cancer patients. They can be observed in the treatment of central nervous system (CNS) diseases as well as in systemic therapy, including whole brain irradiation and chemotherapy and are more often seen due to the better overall survival. This review describes the most frequent acute and chronic therapy-related changes in the CNS and the imaging findings. Acute changes are often reversible while chronic changes can be observed up to several years after treatment. The differentiation of treatment-related from tumor-related changes might be very difficult, although modern imaging modalities such as MR spectroscopy or MR perfusion measurements supply helpful differential diagnostic information. C1 [Essig, M.] Univ Klinikum Erlangen, Abt Neuroradiol, D-91054 Erlangen, Germany. [Dinkel, J.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Zamecnik, C.] Deutsch Krebsforschungszentrum, Abt Radiol, Heidelberg, Germany. RP Essig, M (reprint author), Univ Klinikum Erlangen, Abt Neuroradiol, Schwabachanlage 6, D-91054 Erlangen, Germany. EM mediag@me.com NR 30 TC 0 Z9 0 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-832X J9 RADIOLOGE JI Radiologe PD MAR PY 2012 VL 52 IS 3 BP 229 EP 234 DI 10.1007/s00117-011-2197-8 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 919YU UT WOS:000302368900005 PM 22476705 ER PT J AU Long, M Kalish, LA Neufeld, EJ Grace, RF AF Long, Michelle Kalish, Leslie A. Neufeld, Ellis J. Grace, Rachael F. TI Trends in anti-D immune globulin for childhood immune thrombocytopenia: Usage, response rates, and adverse effects SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID PURPURA; CHILDREN C1 [Long, Michelle; Neufeld, Ellis J.; Grace, Rachael F.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Kalish, Leslie A.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Kalish, Leslie A.; Neufeld, Ellis J.; Grace, Rachael F.] Harvard Univ, Sch Med, Boston, MA USA. [Neufeld, Ellis J.; Grace, Rachael F.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Grace, RF (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave,Karp 8, Boston, MA 02115 USA. EM rachael.grace@childrens.harvard.edu OI Grace, Fergal/0000-0002-3144-5999 FU NCRR NIH HHS [UL1 RR025758, UL1 RR 025758]; NHLBI NIH HHS [K24 HL004184] NR 12 TC 8 Z9 8 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2012 VL 87 IS 3 BP 315 EP 317 DI 10.1002/ajh.22261 PG 3 WC Hematology SC Hematology GA 894TF UT WOS:000300449100016 PM 22190130 ER PT J AU Kamalian, S Kamalian, S Konstas, AA Maas, MB Payabvash, S Pomerantz, SR Schaefer, PW Furie, KL Gonzalez, RG Lev, MH AF Kamalian, Shervin Kamalian, Shahmir Konstas, A. A. Maas, M. B. Payabvash, S. Pomerantz, S. R. Schaefer, P. W. Furie, K. L. Gonzalez, R. G. Lev, M. H. TI CT Perfusion Mean Transit Time Maps Optimally Distinguish Benign Oligemia from True "At-Risk" Ischemic Penumbra, but Thresholds Vary by Postprocessing Technique SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ACUTE STROKE PATIENTS; CEREBRAL-BLOOD-FLOW; SINGULAR-VALUE DECOMPOSITION; INFARCT CORE; COMPUTED-TOMOGRAPHY; LESION VOLUMES; DIFFUSION; MR; DELAY; VALIDATION AB BACKGROUND AND PURPOSE: Various CTP parameters have been used to identify ischemic penumbra. The purpose of this study was to determine the optimal CTP parameter and threshold to distinguish true "at-risk" penumbra from benign oligemia in acute stroke patients without reperfusion. MATERIALS AND METHODS: Consecutive stroke patients were screened and 23 met the following criteria: 1) admission scanning within 9 hours of onset, 2) CTA confirmation of large vessel occlusion, 3) no late clinical or radiographic evidence of reperfusion, 4) no thrombolytic therapy, 5) DWI imaging within 3 hours of CTP, and 6) either CT or MR follow-up imaging. CTP was postprocessed with commercial software packages, using standard and delay-corrected deconvolution algorithms. Relative cerebral blood flow, volume, and mean transit time (rCBF, rCBV and rMTT) values were obtained by normalization to the uninvolved hemisphere. The admission DWI and final infarct were transposed onto the CTP maps and receiver operating characteristic curve analysis was performed to determine optimal thresholds for each perfusion parameter in defining penumbra destined to infarct. RESULTS: Relative and absolute MTT identified penumbra destined to infarct more accurately than CBF or CBV*CBF (P < .01). Absolute and relative MTT thresholds for defining penumbra were 12s and 249% for the standard and 13.5s and 150% for the delay-corrected algorithms, respectively. CONCLUSIONS: Appropriately thresholded absolute and relative MTT-CTP maps optimally distinguish "at-risk" penumbra from benign oligemia in acute stroke patients with large-vessel occlusion and no reperfusion. The precise threshold values may vary, however, depending on the postprocessing technique used for CTP map construction. C1 [Kamalian, Shervin; Kamalian, Shahmir; Konstas, A. A.; Payabvash, S.; Pomerantz, S. R.; Schaefer, P. W.; Gonzalez, R. G.; Lev, M. H.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Maas, M. B.; Furie, K. L.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol GRB285, POB 9657, Boston, MA 02114 USA. EM mlev@partners.org RI Kamalian, Shervin/D-7667-2013; OI Kamalian, Shervin/0000-0001-8962-4773; Kamalian, Shahmir/0000-0002-9640-8144 FU Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) Network; NIH [1 P50 NS051343-01A2, R01NS050041]; Agency for Healthcare Research and Quality (AHRQ) [R01 HS11392-01A1]; Massachusetts General Hospital Clinical Research Center [1 UL1 RR025758-01]; Harvard Clinical and Translational Science Center, from the National Center for Research Resources; SPOTRIAS; National Institutes of Health (NIH/National Institute of Neurological Disorders and Stroke) [one P50 NS051343-01A2]; GE Healthcare; NIH; Penumbra; NIH SPOTRIAS Network [P50 NS051343]; Agency for Healthcare Research and Quality [R01 HS11392]; MGH Clinical Research Center [one UL1 RR025758-01] FX This work was supported by the Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) Network grant funded by the NIH (1 P50 NS051343-01A2 and R01NS050041), Agency for Healthcare Research and Quality grant (AHRQ) R01 HS11392-01A1, and Massachusetts General Hospital Clinical Research Center (No. 1 UL1 RR025758-01), Harvard Clinical and Translational Science Center, from the National Center for Research Resources.; Shahmir Kamalian-RELATED: Grant: SPOTRIAS, Comments: My salary was from Specialized Programs of Translational Research in Acute Stroke (SPOTRIAS) Network grant funded by the National Institutes of Health (NIH/National Institute of Neurological Disorders and Stroke; one P50 NS051343-01A2). Stuart Pornerantz-discloses research support from GE Healthcare not related to CT perfusion. Ramon Gonzalez-RELATED: Grant: NIH,* Penumbra;* UNRELATED: Grants/Grants Pending: NIH,* Penumbra.* Michael Lev-RELATED: Grant: NIH,* GE Healthcare,* Comments: Research funding from GE Healthcare for relevant CT scanning hardware, software, and research assistant support; NIH SPOTRIAS Network grant (P50 NS051343); Agency for Healthcare Research and Quality grant (R01 HS11392); MGH Clinical Research Center (No. one UL1 RR025758-01) Harvard Clinical and Translational Science Center (National Center for Research Resources); UNRELATED.. Consultancy: GE Healthcare, CoAxia, Millennium Pharmaceuticals; Grants/Grants Pending: DOD, NBIB Other: Common stock in GE Healthcare < $10K, Honoraria for various academic Grand Rounds, National Medical/Imaging meetings, << $10K. NR 24 TC 38 Z9 40 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2012 VL 33 IS 3 BP 545 EP 549 DI 10.3174/ajnr.A2809 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 913II UT WOS:000301870300030 PM 22194372 ER PT J AU Dominguez, I Fernandez-del Castillo, C AF Dominguez, Ismael Fernandez-del Castillo, Carlos TI Preoperative platelet-lymphocyte ratio in resected pancreatic ductal carcinoma: is it meaningful? SO AMERICAN JOURNAL OF SURGERY LA English DT Letter ID ADENOCARCINOMA C1 [Dominguez, Ismael] Inst Nacl Ciencias Med Nutr Salvador Zubiran, Dept Surg, Mexico City, DF, Mexico. [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Dominguez, I (reprint author), Inst Nacl Ciencias Med Nutr Salvador Zubiran, Dept Surg, Mexico City, DF, Mexico. NR 4 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAR PY 2012 VL 203 IS 3 BP 412 EP 412 DI 10.1016/j.amjsurg.2009.05.022 PG 1 WC Surgery SC Surgery GA 911GD UT WOS:000301704400060 PM 20579970 ER PT J AU Mengel, M Sis, B Haas, M Colvin, RB Halloran, PF Racusen, LC Solez, K Cendales, L Demetris, AJ Drachenberg, CB Farver, CF Rodriguez, ER Wallace, WD Glotz, D AF Mengel, M. Sis, B. Haas, M. Colvin, R. B. Halloran, P. F. Racusen, L. C. Solez, K. Cendales, L. Demetris, A. J. Drachenberg, C. B. Farver, C. F. Rodriguez, E. R. Wallace, W. D. Glotz, D. CA Banff Meeting Report Writing Comm TI Banff 2011 Meeting Report: New Concepts in Antibody-Mediated Rejection SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Allograft rejection; allograft transplantation; antibody-mediated rejection; Banff classification ID DONOR-SPECIFIC ANTIBODIES; KIDNEY-TRANSPLANT RECIPIENTS; PROTOCOL BIOPSIES; RENAL-ALLOGRAFTS; HLA ANTIBODIES; INJURY; GLOMERULOPATHY; DESENSITIZATION; ALLOANTIBODY; INFLAMMATION AB The 11th Banff meeting was held in Paris, France, from June 5 to 10, 2011, with a focus on refining diagnostic criteria for antibody-mediated rejection (ABMR). The major outcome was the acknowledgment of C4d-negative ABMR in kidney transplants. Diagnostic criteria for ABMR have also been revisited in other types of transplants. It was recognized that ABMR is associated with heterogeneous phenotypes even within the same type of transplant. This highlights the necessity of further refining the respective diagnostic criteria, and is of particular significance for the design of randomized clinical trials. A reliable phenotyping will allow for definition of robust end-points. To address this unmet need and to allow for an evidence-based refinement of the Banff classification, Banff Working Groups presented multicenter data regarding the reproducibility of features relevant to the diagnosis of ABMR. However, the consensus was that more data are necessary and further Banff Working Group activities were initiated. A new Banff working group was created to define diagnostic criteria for ABMR in kidneys independent of C4d. Results are expected to be presented at the 12th Banff meeting to be held in 2013 in Brazil. No change to the Banff classification occurred in 2011. C1 [Mengel, M.; Sis, B.; Solez, K.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Mengel, M.; Sis, B.; Halloran, P. F.] Univ Alberta, Div Nephrol & Immunol, Alberta Transplant Appl Genom Ctr, Dept Med, Edmonton, AB, Canada. [Haas, M.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Colvin, R. B.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Colvin, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Racusen, L. C.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Cendales, L.] Emory Univ, Sch Med, Emory Transplant Ctr, Atlanta, GA USA. [Cendales, L.] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. [Demetris, A. J.] Univ Pittsburgh, Dept Pathol, Div Transplantat Pathol, Pittsburgh, PA USA. [Drachenberg, C. B.] Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. [Farver, C. F.; Rodriguez, E. R.] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44106 USA. [Wallace, W. D.] Univ Calif Los Angeles, Dept Lab Med & Pathol, Los Angeles, CA USA. [Glotz, D.] Hosp St Louis, Dept Nephrol, Paris, France. RP Mengel, M (reprint author), Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. EM mmengel@ualberta.ca RI Halloran, Philip/J-1390-2012 OI Halloran, Philip/0000-0003-1371-1947 FU Astellas; Novartis; Roche; Pfizer; One Lambda; CSL Behring; Transpath; Alexion; Aperio; Philips; Omnyx; University of Alberta; National Kidney Foundation; Renal Pathology Society; Astellas Canada; Genzyme; ORS FX The participants of the 11th Banff Conference gratefully acknowledge the financial support provided by the following companies and institutions: Astellas, Novartis, Roche, Pfizer, One Lambda, CSL Behring, Transpath, Alexion, Aperio, Philips, Omnyx, University of Alberta, National Kidney Foundation and Renal Pathology Society.; Michael Mengel and Banu Sis received a research grant from Astellas Canada in support for the Banff Working Group activities. Michael Mengel is a consultant to Novartis Canada. Denis Glotz received honoraria/speaker's fees from Roche, Novartis, Pfizer, Genzyme, Alexion, ORS, CSL Behring. None of the other authors has any conflicts of interest to disclose as described by the American Journal of Transplantation. NR 41 TC 185 Z9 198 U1 0 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2012 VL 12 IS 3 BP 563 EP 570 DI 10.1111/j.1600-6143.2011.03926.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 899QZ UT WOS:000300832500013 PM 22300494 ER PT J AU Berry, K Ioannou, GN AF Berry, K. Ioannou, G. N. TI Are Patients with Child's A Cirrhosis and Hepatocellular Carcinoma Appropriate Candidates for Liver Transplantation? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Child's A Cirrhosis; hepatocellular carcinoma; liver transplantation; posttransplantation survival; survival benefit ID PERCUTANEOUS RADIOFREQUENCY ABLATION; RANDOMIZED CONTROLLED-TRIAL; TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; SURGICAL RESECTION; ETHANOL INJECTION; SURVIVAL BENEFIT; TRANSARTERIAL CHEMOEMBOLIZATION; CONVENIENT APPROXIMATION; MULTIVARIATE-ANALYSIS; PROGNOSTIC-FACTORS AB We aimed to estimate the survival benefit derived from transplantation in patients with stage II hepatocellular carcinoma (HCC) and Child's A cirrhosis, defined as the mean lifetime with transplantation minus the mean lifetime with treatments other than transplantation. We calculated the posttransplantation survival of all adult, first-time, deceased-donor, liver transplant recipients in the United States since the introduction of the Model for End-Stage Liver Disease based priority system in February 2002 (n = 36 791). We estimated the posttreatment survival of patients with Child's A cirrhosis and stage II HCC treated by radiofrequency ablation (RFA) +/- transarterial chemoembolization (TACE) or surgical resection by conducting a systematic review of the medical literature. In patients with Child's A cirrhosis and stage II HCC, the estimated median survival benefit of liver transplantation compared to RFA +/- TACE was 1.5 months at 3 years (range -3.5 to 5.6) and 5.7 months at 5 years (range 0.711.4), whereas compared to surgical resection it was 0.7 months at 3 years (range -2.9 to 3) and 2.8 months at 5 years (range -4.4 to 5.7). Liver transplantation in patients with stage II HCC and Child's A cirrhosis results in a very low survival benefit and may not constitute optimal use of scarce liver donor organs. C1 [Ioannou, G. N.] Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA USA. [Berry, K.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Ioannou, G. N.] Vet Affairs Puget Sound Hlth Care Syst, Res Enhancement Award Program, Seattle, WA USA. RP Ioannou, GN (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Dept Med, Seattle, WA USA. EM georgei@medicine.washington.edu FU Health Resources and Services Administration [231-00-0115]; Office of Research and Development, Veterans Affairs FX This research was based on data derived from the United Network for Organ Sharing (UNOS) on January 21, 2011. This work was supported in part by Health Resources and Services Administration contract 231-00-0115. G.N.I. was supported by Research Enhancement Award Program, Office of Research and Development, Veterans Affairs. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services. NR 48 TC 30 Z9 30 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2012 VL 12 IS 3 BP 706 EP 717 DI 10.1111/j.1600-6143.2011.03853.x PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 899QZ UT WOS:000300832500027 PM 22123435 ER PT J AU Stagakis, E Bertsias, G Verginis, P Nakou, M Hatziapostolou, M Sidiropoulos, P Goulielmos, G Iliopoulos, D Boumpas, DT AF Stagakis, E. Bertsias, G. Verginis, P. Nakou, M. Hatziapostolou, Maria Sidiropoulos, P. Goulielmos, G. Iliopoulos, D. Boumpas, D. T. TI REGULATION OF T CELL HYPERACTIVITY IN SLE: THE NEGATIVE CO-STIMULATORY MOLECULE PD-1 REGULATES MIR-21 EXPRESSION IN SLE T LYMPHOCYTES SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 32nd European Workshop for Rheumatology Research CY FEB 23-25, 2012 CL Stockholm, SWEDEN C1 [Stagakis, E.; Bertsias, G.; Verginis, P.; Nakou, M.; Boumpas, D. T.] Univ Crete, Sch Med, Lab Autoimmun & Inflammat, Iraklion, Greece. [Hatziapostolou, Maria; Sidiropoulos, P.; Goulielmos, G.; Iliopoulos, D.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2012 VL 71 SU 1 BP A58 EP A58 DI 10.1136/annrheumdis-2011-201236.18 PG 1 WC Rheumatology SC Rheumatology GA 919KF UT WOS:000302323600133 ER PT J AU Bernstein, EJ Isakova, T Sullivan, ME Chibnik, LB Bazari, H Wolf, MS Kay, J AF Bernstein, Elana J. Isakova, Tamara Sullivan, Mary E. Chibnik, Lori B. Bazari, Hasan Wolf, Myles S. Kay, Jonathan TI HYPOPHOSPHATEMIA IS ASSOCIATED WITH NEPHROGENIC SYSTEMIC FIBROSIS: A CASE-CONTROL STUDY SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 32nd European Workshop for Rheumatology Research CY FEB 23-25, 2012 CL Stockholm, SWEDEN C1 [Bernstein, Elana J.] Hosp Special Surg, New York, NY 10021 USA. [Isakova, Tamara; Wolf, Myles S.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Sullivan, Mary E.; Bazari, Hasan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chibnik, Lori B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kay, Jonathan] Univ Massachusetts, Sch Med, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2012 VL 71 SU 1 DI 10.1136/annrheumdis-2011-201237.26 PG 1 WC Rheumatology SC Rheumatology GA 919KF UT WOS:000302323600166 ER PT J AU Krasoudaki, E Stagakis, E Loupasakis, K Papagianni, A Alexopoulos, E Bertsias, G Iliopoulos, D Boumpas, DT AF Krasoudaki, E. Stagakis, E. Loupasakis, K. Papagianni, A. Alexopoulos, E. Bertsias, G. Iliopoulos, D. Boumpas, D. T. TI IDENTIFICATION OF A NOVEL MICRORNA-GENE CIRCUIT IN HUMAN LUPUS NEPHRITIS: EVIDENCE FOR MODULATION OF KALLIKREIN GENES BY MIR-422A SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 32nd European Workshop for Rheumatology Research CY FEB 23-25, 2012 CL Stockholm, SWEDEN C1 [Krasoudaki, E.; Stagakis, E.; Bertsias, G.; Boumpas, D. T.] Univ Crete, Sch Med, Lab Autoimmun & Inflammat, Iraklion, Greece. [Loupasakis, K.; Iliopoulos, D.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Papagianni, A.; Alexopoulos, E.] Aristotle Univ Thessaloniki, Dept Nephrol, Gen Hosp Thessaloniki Hippokrat, GR-54006 Thessaloniki, Greece. NR 0 TC 0 Z9 0 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR PY 2012 VL 71 SU 1 DI 10.1136/annrheumdis-2011-201236.1 PG 1 WC Rheumatology SC Rheumatology GA 919KF UT WOS:000302323600116 ER PT J AU Mountz, JD Li, J Hsu, HC AF Mountz, John D. Li, Jun Hsu, Hui-Chen TI Systemic autoimmunity caused by fas deficiency in macrophages: A new perspective on the first identified autoimmunity gene SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID CELL-DEATH; MICE; LIGAND; ACTIVATION; APOPTOSIS; DISEASE; ANTIGEN; DEGRADATION; PREVENTION; ABLATION C1 [Mountz, John D.] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Mountz, John D.; Hsu, Hui-Chen] Birmingham VA Med Ctr, Birmingham, AL USA. RP Mountz, JD (reprint author), Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, 701 S 19th St,Room 473 LHRB, Birmingham, AL 35294 USA. EM jdmountz@uab.edu FU NIAID NIH HHS [R01-AI-083705-01A2, 1-AI-071110-01A1, R01-AI-71110-02S1] NR 18 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAR PY 2012 VL 64 IS 3 BP 609 EP 612 DI 10.1002/art.34321 PG 4 WC Rheumatology SC Rheumatology GA 899SH UT WOS:000300835900003 PM 22139895 ER PT J AU Kezic, JM Davey, MP Glant, TT Rosenbaum, JT Rosenzweig, HL AF Kezic, Jelena M. Davey, Michael P. Glant, Tibor T. Rosenbaum, James T. Rosenzweig, Holly L. TI Interferon-gamma regulates discordant mechanisms of uveitis versus joint and axial disease in a murine model resembling spondylarthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PROTEOGLYCAN-INDUCED ARTHRITIS; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; ENDOTOXIN-INDUCED UVEITIS; ACUTE ANTERIOR UVEITIS; ANKYLOSING-SPONDYLITIS; T-CELLS; INTRAVITAL MICROSCOPY; GENETIC-CONTROL; SYNOVIAL-FLUID; BALB/C MICE AB Objective The spondylarthritides (such as ankylosing spondylitis) are multisystem inflammatory diseases that frequently result in uveitis. Despite the common co-occurrence of uveitis with arthritis, there has been no explanation for the susceptibility of the eye to inflammation. Using an innovative intravital videomicroscopic approach, we discovered the coexistence of uveitis with axial and peripheral joint inflammation in mice immunized with cartilage proteoglycan (PG). The aim of this study was to elucidate the characteristics of uveitis and test the impact of interferon-? (IFN?) deficiency on the eye versus the joint and spine. Methods. Female T cell receptor (TCR)-transgenic mice or IFN gamma -knockout mice crossed to TCR-transgenic mice were immunized with PG. Uveitis was assessed by intravital videomicroscopy and histology. The clinical and histopathologic severity of arthritis and spondylitis were evaluated. The bone remodeling process within the spine was assessed by whole-body near-infrared imaging. Immunoblotting and immunofluorescence staining were used to examine the expression of PG and ADAMTS-5 and to examine the cellular composition of eyes with uveitis. Results. PG neoepitopes along with the aggrecanase ADAMTS-5 were present in the eye, as they were the joint. Anterior uveitis developed in response to PG immunization. The cellular infiltrate consisted mainly of neutrophils and eosinophils. Unexpectedly, IFN gamma deficiency markedly exacerbated uveitis while ameliorating joint and spine disease, indicating divergent mechanisms that drive diseases in the eye versus the joints and spine. Conclusion. This study provides the first detailed description of a murine disease model in which uveitis coincides with arthritis and spondylitis. Our observations provide a great opportunity for understanding the pathogenesis of a relatively common but poorly understood disease. C1 [Kezic, Jelena M.; Davey, Michael P.; Rosenbaum, James T.; Rosenzweig, Holly L.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Davey, Michael P.; Rosenzweig, Holly L.] Portland VA Med Ctr, Portland, OR 97239 USA. [Glant, Tibor T.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Rosenzweig, HL (reprint author), Oregon Hlth & Sci Univ, Mail Stop L 467 AD,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM rosenzwh@ohsu.edu FU NIH (National Eye Institute) [EY-021733, EY-019020, EY-019604]; William and Mary Bauman Foundation; Stan and Madelle Rosenfeld Family Trust; William C. Kuzell Foundation; American College of Rheumatology Research and Education Foundation; Research to Prevent Blindness Foundation; Novartis; Amgen FX Supported by the NIH (National Eye Institute grants EY-021733, EY-019020, and EY-019604), the William and Mary Bauman Foundation, the Stan and Madelle Rosenfeld Family Trust, and the William C. Kuzell Foundation. Dr. Rosenzweig's work was also supported by the American College of Rheumatology Research and Education Foundation and the Research to Prevent Blindness Foundation.; Dr. Rosenbaum has received consulting fees, speaking fees, and/or honoraria from Novartis and Amgen (less than $10,000 each). NR 44 TC 7 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAR PY 2012 VL 64 IS 3 BP 762 EP 771 DI 10.1002/art.33404 PG 10 WC Rheumatology SC Rheumatology GA 899SH UT WOS:000300835900020 PM 21987263 ER PT J AU Schumacher, HR Sundy, JS Terkeltaub, R Knapp, HR Mellis, SJ Stahl, N Yancopoulos, GD Soo, Y King-Davis, S Weinstein, SP Radin, AR AF Schumacher, H. Ralph, Jr. Sundy, John S. Terkeltaub, Robert Knapp, Howard R. Mellis, Scott J. Stahl, Neil Yancopoulos, George D. Soo, Yuhwen King-Davis, Shirletta Weinstein, Steven P. Radin, Allen R. CA 0619 Study Grp TI Rilonacept (interleukin-1 trap) in the prevention of acute gout flares during initiation of urate-lowering therapy: Results of a phase II randomized, double-blind, placebo-controlled trial SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ALLOPURINOL; ARTHRITIS; MANAGEMENT; CARE; INHIBITION; CRYSTALS; ANAKINRA; RISK AB Objective To evaluate the interleukin-1 inhibitor rilonacept (Interleukin-1 Trap) for prevention of gout flares occurring in the first few months following initiation of urate-lowering therapy. Methods. In this double-blind study, adult patients with hyperuricemia and gout were randomized to receive rilonacept administered subcutaneously once per week (loading dose 320 mg followed by 160 mg weekly) or placebo, and started on allopurinol (300 mg/day, titrated to serum urate <6 mg/dl). At study visits, physical and laboratory assessments were performed and information on any adverse events was ascertained. Results. Baseline characteristics were similar between the rilonacept and placebo groups (n = 41 and n = 42, respectively). The mean number of gout flares per patient through week 12 (primary efficacy end point) was markedly lower in the rilonacept group than in the placebo group (0.15 [6 flares] versus 0.79 [33 flares]; P = 0.0011). Fewer flares were observed with rilonacept as early as 4 weeks after initiation of treatment (P = 0.007). The proportion of patients experiencing a flare during the 12 weeks was lower in the rilonacept group than in the placebo group (14.6% versus 45.2%; P = 0.0037). No rebound in the flare rate was observed for 6 weeks after discontinuation of rilonacept or placebo at week 16. Adverse events were similar between groups, and no deaths or serious infectious adverse events were reported; the most common adverse events were infections (14.6% and 26.2% of rilonacept- and placebo-treated patients, respectively) and musculoskeletal disorders (14.6% and 21.4%, respectively). A higher percentage of rilonacept-treated patients (98%) compared with placebo-treated patients (79%) completed the primary 12-week evaluation period (P = 0.015). Conclusion. The current findings indicate that rilonacept significantly reduces the frequency of gout flares during the initial period of treatment with urate-lowering therapy, with a favorable safety profile. C1 [Schumacher, H. Ralph, Jr.] Univ Penn, VA Med Ctr, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Sundy, John S.] Duke Univ, Med Ctr, Durham, NC USA. [Terkeltaub, Robert] Univ Calif San Diego, San Diego, CA 92103 USA. [Terkeltaub, Robert] San Diego VA Med Ctr, San Diego, CA USA. [Knapp, Howard R.] Montana State Univ, Billings, MT USA. [Mellis, Scott J.; Stahl, Neil; Yancopoulos, George D.; Soo, Yuhwen; King-Davis, Shirletta; Weinstein, Steven P.; Radin, Allen R.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. RP Schumacher, HR (reprint author), Univ Penn, VA Med Ctr, 151K,Univ & Woodland Avenues, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu FU Regeneron Pharmaceuticals, Inc.; Regeneron; Takeda; Savient; Ardea; Pfizer; Xoma; Novartis; Regeneron through Duke University; URL Pharma FX Supported by Regeneron Pharmaceuticals, Inc.; Dr. Schumacher has received consulting fees, speaking fees, and/or honoraria from Regeneron, Takeda, Savient, Ardea, Pfizer, Xoma, and Novartis (less than $10,000 each). Dr. Sundy has received consulting fees from Regeneron and Novartis (less than $10,000 each) and receives sponsored research grants from Regeneron through Duke University. Dr. Terkeltaub has received consulting fees, speaking fees, and/or honoraria from Regeneron, Novartis, and URL Pharma (less than $10,000 each) and has served as a paid consultant to the investment analysts Guidepoint Global and the Coleman Group. Drs. Mellis, Stahl, Yancopoulos, Soo, Weinstein, and Radin and Ms King-Davis own stock in Regeneron. Dr. Mellis holds a patent, licensed to Regeneron, for the use of interleukin-1 antagonists to treat gout. NR 26 TC 43 Z9 45 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD MAR PY 2012 VL 64 IS 3 BP 876 EP 884 DI 10.1002/art.33412 PG 9 WC Rheumatology SC Rheumatology GA 899SH UT WOS:000300835900032 PM 22223180 ER PT J AU Gardiner, DM Holmes, LB AF Gardiner, David M. Holmes, Lewis B. TI Hypothesis: Terminal transverse limb defects with "nubbins" represent a regenerative process during limb development in human fetuses SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE terminal transverse limb defects; nubbins; regeneration ID FINGERTIP; INJURIES; DAUGHTER; CELLS; MICE AB BACKGROUND Terminal transverse limb defects with nubbins occur in one arm at one of several levels (distal humerus, proximal forearm, wrist, and at the metacarpal-phalangeal joint in the hand). The associated nubbins contain osteocartilaginous tissue and small nails and are not associated with evidence of amnion disruption. METHODS: We present affected newborn infants whose terminal transverse limb defects are at one of these three levels: proximal forearm, elbow, or metacarpal-phalangeal joint. RESULTS: We hypothesize that the presence of residual digit-like structures reflects a regenerative process that has occurred during limb development in these infants. DISCUSSION: Only limited regeneration of digit-like structures can occur in the human fetus. Birth Defects Research (Part A) 94:129-133, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Holmes, Lewis B.] Harvard Univ, Sch Med, Dept Pediat, Genet Unit,MassGen Hosp Children, Boston, MA 02114 USA. [Gardiner, David M.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA. RP Holmes, LB (reprint author), Harvard Univ, Sch Med, Dept Pediat, Genet Unit,MassGen Hosp Children, 175 Cambridge St,Room 504, Boston, MA 02114 USA. EM holmes.lewis@mgh.harvard.edu NR 24 TC 1 Z9 1 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAR PY 2012 VL 94 IS 3 BP 129 EP 133 DI 10.1002/bdra.22876 PG 5 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 907QX UT WOS:000301433600002 PM 22287196 ER PT J AU Lui, KO Bu, L Li, RA Chan, CW AF Lui, Kathy O. Bu, Lei Li, Ronald A. Chan, Camie W. TI Pluripotent Stem Cell-based Heart Regeneration: From the Developmental and Immunological Perspectives SO BIRTH DEFECTS RESEARCH PART C-EMBRYO TODAY-REVIEWS LA English DT Review DE stem cells; ESC; iPSC; heart development; immunogenicity; regenerative medicine; transplantation ID REGULATORY T-CELLS; BHLH TRANSCRIPTION FACTOR; MODIFIED MESSENGER-RNA; CARDIOVASCULAR PROGENITORS; MYOCARDIAL-INFARCTION; HUMAN FIBROBLASTS; COSTIMULATION BLOCKADE; CARDIAC MORPHOGENESIS; TOLERANCE INDUCTION; SMOOTH-MUSCLE AB Heart diseases such as myocardial infarction cause massive loss of cardiomyocytes, but the human heart lacks the innate ability to regenerate. In the adult mammalian heart, a resident progenitor cell population, termed epicardial progenitors, has been identified and reported to stay quiescent under uninjured conditions; however, myocardial infarction induces their proliferation and de novo differentiation into cardiac cells. It is conceivable to develop novel therapeutic approaches for myocardial repair by targeting such expandable sources of cardiac progenitors, thereby giving rise to new muscle and vasculatures. Human pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells can self-renew and differentiate into the three major cell types of the heart, namely cardiomyocytes, smooth muscle, and endothelial cells. In this review, we describe our current knowledge of the therapeutic potential and challenges associated with the use of pluripotent stem cell and progenitor biology in cell therapy. An emphasis is placed on the contribution of paracrine factors in the growth of myocardium and neovascularization as well as the role of immunogenicity in cell survival and engraftment. (Part C) 96:98-107, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Lui, Kathy O.; Bu, Lei; Li, Ronald A.; Chan, Camie W.] Univ Hong Kong, LKS Fac Med, Stem Cell & Regenerat Med Consortium, Pokfulam, Hong Kong, Peoples R China. [Lui, Kathy O.; Bu, Lei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Lui, Kathy O.; Bu, Lei] Harvard Stem Cell Inst, Boston, MA 02114 USA. [Li, Ronald A.] Univ Hong Kong, LKS Fac Med, Dept Med, Pokfulam, Hong Kong, Peoples R China. [Li, Ronald A.] Univ Hong Kong, LKS Fac Med, Dept Physiol, Pokfulam, Hong Kong, Peoples R China. [Chan, Camie W.] Univ Hong Kong, LKS Fac Med, Dept Anat, Pokfulam, Hong Kong, Peoples R China. [Li, Ronald A.] Mt Sinai Sch Med, Cardiovasc Res Ctr, New York, NY USA. RP Chan, CW (reprint author), Univ Hong Kong, LKS Fac Med, Stem Cell & Regenerat Med Consortium, Pokfulam, Hong Kong, Peoples R China. EM ronald.li@mssm.edu; camchan@hku.hk RI Lui, Kathy O./E-4883-2015 OI Lui, Kathy O./0000-0002-1616-3643 NR 95 TC 4 Z9 6 U1 2 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1542-975X J9 BIRTH DEFECTS RES C JI Birth Defects Res. Part C-Embryo Today-Rev. PD MAR PY 2012 VL 96 IS 1 BP 98 EP 108 DI 10.1002/bdrc.21004 PG 11 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 918YO UT WOS:000302287800008 PM 22457181 ER PT J AU Gee, AO Baker, BM Silverstein, AM Montero, G Esterhai, JL Mauck, RL AF Gee, Albert O. Baker, Brendon M. Silverstein, Amy M. Montero, Giana Esterhai, John L. Mauck, Robert L. TI Fabrication and evaluation of biomimetic-synthetic nanofibrous composites for soft tissue regeneration SO CELL AND TISSUE RESEARCH LA English DT Article DE Tissue engineering; Mechanical properties; Nanofiber; Scaffolds; Electrospinning; Mesenchymal stem cells ID HUMAN ARTICULAR-CARTILAGE; CROSS-LINKING AGENT; ENGINEERING SCAFFOLDS; IN-VITRO; EXTRACELLULAR-MATRIX; CELLULAR INFILTRATION; ELECTROSPUN SCAFFOLDS; GELATIN MICROSPHERES; COLLAGEN NANOFIBERS; BIOLOGICAL TISSUE AB Electrospun scaffolds hold promise for the regeneration of dense connective tissues, given their nanoscale topographies, provision of directional cues for infiltrating cells and versatile composition. Synthetic slow-degrading scaffolds provide long-term mechanical support and nanoscale instructional cues; however, these scaffolds suffer from a poor infiltration rate. Alternatively, nanofibrous constructs formed from natural biomimetic materials (such as collagen) rapidly infiltrate but provide little mechanical support. To take advantage of the positive features of these constructs, we have developed a composite scaffold consisting in both a biomimetic fiber fraction (i.e., Type I collagen nanofibers) together with a traditional synthetic (i.e., poly-[epsilon-caprolactone], PCL) fiber fraction. We hypothesize that inclusion of biomimetic elements will improve initial cell adhesion and eventual scaffold infiltration, whereas the synthetic elements will provide controlled and long-term mechanical support. We have developed a method of forming and crosslinking collagen nanofibers by using the natural crosslinking agent genipin (GP). Further, we have formed composites from collagen and PCL and evaluated the long-term performance of these scaffolds when seeded with mesenchymal stem cells. Our results demonstrate that GP crosslinking is cytocompatible and generates stable nanofibrous type I collagen constructs. Composites with varying fractions of the biomimetic and synthetic fiber families are formed and retain their collagen fiber fractions during in vitro culture. However, at the maximum collagen fiber fractions (20%), cell ingress is limited compared with pure PCL scaffolds. These results provide a new foundation for the development and optimization of biomimetic/synthetic nanofibrous composites for in vivo tissue engineering. C1 [Gee, Albert O.; Baker, Brendon M.; Silverstein, Amy M.; Montero, Giana; Esterhai, John L.; Mauck, Robert L.] Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. [Baker, Brendon M.; Silverstein, Amy M.; Montero, Giana; Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Esterhai, John L.; Mauck, Robert L.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Mauck, RL (reprint author), Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, 424G Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu FU National Institutes of Health [R01 AR056624]; Department of Veterans' Affairs [I01 RX000174]; Penn Center for Musculoskeletal Disorders [P30 AR050950]; Penn Department of Orthopaedic Surgery; National Science Foundation FX This work was supported by the National Institutes of Health (R01 AR056624, RLM), The Department of Veterans' Affairs (I01 RX000174, JLE) and the Penn Center for Musculoskeletal Disorders (P30 AR050950, RLM). Additional support was provided by the Penn Department of Orthopaedic Surgery (AOG) and a graduate fellowship from the National Science Foundation (BMB). NR 67 TC 11 Z9 11 U1 3 U2 45 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD MAR PY 2012 VL 347 IS 3 BP 803 EP 813 DI 10.1007/s00441-011-1308-1 PG 11 WC Cell Biology SC Cell Biology GA 916YG UT WOS:000302138500027 PM 22287042 ER PT J AU Moriggi, L Yaseen, MA Helm, L Caravan, P AF Moriggi, Loick Yaseen, Mohammad A. Helm, Lothar Caravan, Peter TI Serum Albumin Targeted, pH-Dependent Magnetic Resonance Relaxation Agents SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE gadolinium; imaging; imaging agents; second-sphere relaxation; serum albumin ID MRI CONTRAST AGENTS; SPHERE WATER-MOLECULES; N-B TRANSITION; TUMOR PH; O-17 NMR; IN-VIVO; RELAXIVITY; BINDING; COMPLEXES; GADOLINIUM AB The objective of this work was the synthesis of serum albumin targeted, GdIII-based magnetic resonance imaging (MRI) contrast agents exhibiting a strong pH-dependent relaxivity. Two new complexes (Gd-glu and Gd-bbu) were synthesized based on the DO3A macrocycle modified with three carboxyalkyl substituents a to the three ring nitrogen atoms, and a biphenylsulfonamide arm. The sulfonamide nitrogen coordinates the Gd in a pH-dependent fashion, resulting in a decrease in the hydration state, q, as pH is increased and a resultant decrease in relaxivity (r1). In the absence of human serum albumin (HSA), r1 increases from 2.0 to 6.0 mM-1?s-1 for Gd-glu and from 2.4 to 9.0 mM-1?s-1 for Gd-bbu from pH 5 to 8.5 at 37?degrees C, 0.47 T, respectively. These complexes (0.2 mM) are bound (>98.9?%) to HSA (0.69 mM) over the pH range 58.5. Binding to albumin increases the rotational correlation time and results in higher relaxivity. The r1 increased 120?% (pH 5) and 550?% (pH 8.5) for Gd-glu and 42?% (pH 5) and 260?% (pH 8.5) for Gd-bbu. The increases in r1 at pH 5 were unexpectedly low for a putative slow tumbling q=2 complex. The Gd-bbu system was investigated further. At pH 5, it binds in a stepwise fashion to HSA with dissociation constants Kd1=0.65, Kd2=18, Kd3=1360 mu M. The relaxivity at each binding site was constant. Luminescence lifetime titration experiments with the EuIII analogue revealed that the inner-sphere water ligands are displaced when the complex binds to HSA resulting in lower than expected r1 at pH 5. Variable pH and temperature nuclear magnetic relaxation dispersion (NMRD) studies showed that the increased r1 of the albumin-bound q=0 complexes is due to the presence of a nearby water molecule with a long residency time (12 ns). The distance between this water molecule and the Gd ion changes with pH resulting in albumin-bound pH-dependent relaxivity. C1 [Moriggi, Loick; Yaseen, Mohammad A.; Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Moriggi, Loick; Yaseen, Mohammad A.; Caravan, Peter] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Helm, Lothar] Ecole Polytech Fed Lausanne, BCH, Inst Chim Mol & Biol, CH-1015 Lausanne, Switzerland. RP Caravan, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU Swiss National Science Foundation [PBELP2-130907]; National Institute of Biomedical Imaging and Bio-engineering [R01EB009062, R21EB009738]; National Institute of Neurological Disorders and Stroke [R01NS057476] FX L.M. acknowledges the Swiss National Science Foundation for a fellowship (PBELP2-130907). Fabrice Yerly is thanked for providing the program VISUALISEUR/OPTIMISEUR, version 2.3.7 (2010) for least-squares fitting of the NMRD data and the pKa experiment. We thank Zhaoda Zhang for helpful discussions regarding the synthesis. This work was supported by the National Institute of Biomedical Imaging and Bio-engineering (award numbers: R01EB009062 and R21EB009738) and the National Institute of Neurological Disorders and Stroke (R01NS057476). NR 61 TC 15 Z9 15 U1 1 U2 34 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 0947-6539 EI 1521-3765 J9 CHEM-EUR J JI Chem.-Eur. J. PD MAR PY 2012 VL 18 IS 12 BP 3675 EP 3686 DI 10.1002/chem.201103344 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 907UR UT WOS:000301444900028 PM 22328098 ER PT J AU Blankstein, R Ahmed, W Bamberg, F Rogers, IS Schlett, CL Nasir, K Fontes, J Tawakol, A Brady, TJ Nagurney, JT Hoffmann, U Truong, QA AF Blankstein, Ron Ahmed, Waleed Bamberg, Fabian Rogers, Ian S. Schlett, Christopher Lothar Nasir, Khurram Fontes, Joao Tawakol, Ahmed Brady, Thomas J. Nagurney, John T. Hoffmann, Udo Truong, Quynh A. TI Comparison of Exercise Treadmill Testing With Cardiac Computed Tomography Angiography Among Patients Presenting to the Emergency Room With Chest Pain The Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE cardiovascular CT; exercise testing; coronary artery disease; stress testing ID CORONARY-ARTERY-DISEASE; ASSOCIATION TASK-FORCE; 2002 GUIDELINE UPDATE; HEART-ASSOCIATION; AMERICAN-COLLEGE; CARDIOVASCULAR RISK; DEPARTMENT PATIENTS; PROGNOSTIC VALUE; TRIAL; CARDIOLOGY AB Background-The aims of our study were to (1) examine how data from exercise treadmill testing (ETT) can identify patients who have coronary plaque or stenosis, using CT angiography (CTA) as the reference standard, and (2) identify patient characteristics that may be used in selecting ETT versus CTA. Methods and Results-The Rule Out Myocardial Infarction Using Computer-Assisted Tomography (ROMICAT) trial was an observational cohort study of acute chest pain patients presenting to the emergency department with normal initial troponin and a nonischemic ECG. Univariate and multivariable analyses were performed to assess the relationship of baseline clinical data and ETT parameters with coronary plaque and stenosis on CTA. Of the 220 patients who had ETT (mean age, 51 years; 63% men), 21 (10%) had positive results. A positive ETT had a sensitivity of 30% and specificity of 93% to detect >50% stenosis. The sensitivity increased to 83% after excluding uninterpretable segments and evaluating the ability to detect a >70% stenosis. Predictors of plaque included older age, male sex, diabetes, hypertension, hyperlipidemia, lower functional capacity, and a lower Duke Treadmill Score. Both a positive ETT and a low Duke Treadmill Score were significant univariate and multivariable predictors of stenosis >50% on CTA Whereas the prevalence of stenosis by CTA was greater among patients with more risk factors, coronary stenosis was not present among men <40 years old or women <50 years old or individuals who achieved at least 13 metabolic equivalents on ETT. Conclusions-Among low-to intermediate-risk patients with acute chest pain, a positive ETT has a limited sensitivity but high specificity for the detection of >50% stenosis by CTA. Although patients with a high number of clinical risk factors are more likely to have obstructive coronary artery disease, those who are young or who would be expected to have a very high exercise capacity are unlikely to have coronary stenosis and therefore may benefit from initial ETT testing instead of CTA. (Circ Cardiovasc Imaging. 2012;5:233-242.) C1 [Blankstein, Ron] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Sch Med,Dept Med, Boston, MA 02115 USA. [Nasir, Khurram] Yale Univ, Sect Cardiovasc Med, New Haven, CT USA. [Fontes, Joao] NHLBI, Framingham, MA USA. [Fontes, Joao] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Ahmed, Waleed; Bamberg, Fabian; Rogers, Ian S.; Schlett, Christopher Lothar; Tawakol, Ahmed; Brady, Thomas J.; Hoffmann, Udo; Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. [Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Tawakol, Ahmed; Brady, Thomas J.; Truong, Quynh A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Nagurney, John T.; Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Blankstein, R (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, Sch Med,Dept Med, 75 Francis St,Room Shapiro 5096, Boston, MA 02115 USA. EM rblankstein@parters.org FU National Institutes of Health (NIH) [R01 HL080053, T32HL076136, K23HL098370, L30HL093896] FX This work was supported by the National Institutes of Health (NIH) (R01 HL080053). Drs Blankstein, Ahmed, Rogers, and Truong received support from NIH grant T32HL076136. Dr Truong also received support from NIH grants K23HL098370 and L30HL093896. NR 26 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-9651 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD MAR PY 2012 VL 5 IS 2 BP 233 EP 242 DI 10.1161/CIRCIMAGING.111.969568 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 916SE UT WOS:000302122700012 PM 22308274 ER PT J AU Reynolds, MR Gunnarsson, CL Hunter, TD Ladapo, JA March, JL Zhang, MD Hao, SC AF Reynolds, Matthew R. Gunnarsson, Candace L. Hunter, Tina D. Ladapo, Joseph A. March, Jamie L. Zhang, Mingdong Hao, Steven C. TI Health Outcomes With Catheter Ablation or Antiarrhythmic Drug Therapy in Atrial Fibrillation Results of a Propensity-Matched Analysis SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE fibrillation; catheter ablation; stroke; heart failure; antiarrhythmia agents ID QUALITY-OF-LIFE; HEART-FAILURE; RISK-FACTORS; RADIOFREQUENCY ABLATION; LONG-TERM; FOLLOW-UP; STROKE; ANTICOAGULATION; PREVALENCE; MORTALITY AB Background-Patients with atrial fibrillation (AF) face significant risks of stroke and heart failure. The objective of this study was to determine whether AF ablation reduces the long-term risk of stroke or heart failure compared with antiarrhythmic drug therapy. Methods and Results-A coding algorithm was used to identify AF patients treated with catheter ablation (n=3194) or antiarrhythmic drugs without ablation (n=6028) between 2005 and 2009 using The MarketScan Research Database from Thomson Reuters From this sample, 801 pairs were propensity matched, based on 15 demographic and clinical characteristics and baseline medication use. Rates of stroke/transient ischemic attack (TIA) and heart failure hospitalizations for up to 3 years were examined. Patients treated with catheter ablation had a significantly lower rate of stroke or TIA (3.4% per year) than a group of patients with AF managed with antiarrhythmic drugs only (5.5% per year), with an unadjusted hazard ratio of 0.62 (95% CI, 0.44-0.86; P=0.005). The rates for heart failure hospitalization were 1.5% per year in the ablation group and 2.2% per year in the antiarrhythmic drug group, with an unadjusted hazard ratio of 0.69 (95% CI, 0.42-1.15; P=0.158). These results were minimally altered in Cox proportional hazards models, which further adjusted for potential confounders not well balanced by the propensity matching. Conclusions-In a large propensity-matched community sample, AF ablation was associated with a reduced risk of stroke/TIA and no significant difference in heart failure hospitalizations compared with antiarrhythmic drug therapy. These findings require confirmation with randomized study designs. (Circ Cardiovasc Qual Outcomes. 2012;5:171-181.) C1 [Reynolds, Matthew R.] Beth Israel Deaconess Med Ctr, Dept Cardiol, Boston, MA 02215 USA. [Reynolds, Matthew R.] VA Boston Healthcare Syst, Boston, MA USA. [Gunnarsson, Candace L.; Hunter, Tina D.] S2 Stat Solut Inc, Cincinnati, OH 45241 USA. [Ladapo, Joseph A.] NYU, Sch Med, Dept Med, New York, NY USA. [March, Jamie L.; Zhang, Mingdong] Biosense Webster Inc, Diamond Bar, CA USA. [Hao, Steven C.] Sutter Pacific Med Fdn, San Francisco, CA USA. RP Gunnarsson, CL (reprint author), S2 Stat Solut Inc, 11176 Main St, Cincinnati, OH 45241 USA. EM candaceg@s2stats.com OI Ladapo, Joseph/0000-0002-8518-4800 FU Biosense Webster, Inc, Diamond Bar, CA; Biosense Webster, Inc; Sanofi Aventis; St Jude Medical; Medtronic, Inc. FX This study was funded by Biosense Webster, Inc, Diamond Bar, CA.; Dr Reynolds has received research grant support from Biosense Webster, Inc, and Sanofi Aventis; and consulting fees from Biosense Webster, Inc, Sanofi Aventis, St Jude Medical, and Medtronic, Inc. Drs Gunnarsson and Hunter are employed by and Dr Ladapo is a paid consultant to S2 Statistical Solutions, Inc, which is a paid consultant firm to Biosense Webster, Inc. Ms March and Dr Zhang are employees of Biosense Webster, Inc. Dr Hao has received consulting fees from Biosense Webster, Inc, and Medtronic, Inc. NR 25 TC 35 Z9 37 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2012 VL 5 IS 2 BP 171 EP U71 DI 10.1161/CIRCOUTCOMES.111.963108 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916RG UT WOS:000302120300010 PM 22373904 ER PT J AU Yeh, RW Normand, SLT Wang, Y Barr, CD Dominici, F AF Yeh, Robert W. Normand, Sharon-Lise T. Wang, Yun Barr, Christopher D. Dominici, Francesca TI Geographic Disparities in the Incidence and Outcomes of Hospitalized Myocardial Infarction Does a Rising Tide Lift All Boats? SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE myocardial infarction; Medicare; trends; disparities ID FEE-FOR-SERVICE; UNITED-STATES; REGIONAL-VARIATION; CARDIOVASCULAR-DISEASE; CORONARY-ANGIOGRAPHY; MORTALITY-RATES; HEART-DISEASE; SMOKING BAN; US ADULTS; TRENDS AB Background-Improvements in prevention have led to declines in incidence and mortality of myocardial infarction (MI) in selected populations. However, no studies have examined regional differences in recent trends in MI incidence, and few have examined whether known regional disparities in MI care have narrowed over time. Methods and Results-We compared trends in incidence rates of MI, associated procedures and mortality for all US Census Divisions (regions) in Medicare fee-for-service patients between 2000-2008 (292 773 151 patient-years). Two-stage hierarchical models were used to account for patient characteristics and state-level random effects. To assess trends in geographic disparities, we calculated changes in between-state variance for outcomes over time. Although the incidence of MI declined in all regions (P<0.001 for trend for each) between 2000-2008, adjusted rates of decline varied by region (annual declines ranging from 2.9-6.1%). Widening geographic disparities, as measured by percent change of between-state variance from 2000-2008, were observed for MI incidence (37.6% increase, P=0.03) and percutaneous coronary intervention rates (31.4% increase, P=0.06). Significant declines in risk-adjusted 30-day mortality were observed in all regions, with the fastest declines observed in states with higher baseline mortality rates. Conclusions-In a large contemporary analysis of geographic trends in MI epidemiology, the incidence of MI and associated mortality declined significantly in all US Census Divisions between 2000-2008. Although geographic disparities in MI incidence may have increased, regional differences in MI-associated mortality have narrowed. (Circ Cardiovasc Qual Outcomes. 2012;5:197-204.) C1 [Yeh, Robert W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, Boston, MA 02114 USA. [Normand, Sharon-Lise T.; Barr, Christopher D.; Dominici, Francesca] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Normand, Sharon-Lise T.; Wang, Yun] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Barr, Christopher D.] Harvard Univ, John F Kennedy Sch Govt, Cambridge, MA 02138 USA. RP Yeh, RW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Med, GRB8-843,55 Fruit St, Boston, MA 02114 USA. EM ryeh@partners.org FU National Institute of Environmental Health Sciences [R01ES012054]; Environmental Protection Agency [EPA RD83479801, EPA RD83489401] FX This project was supported by Award No. R01ES012054 from the National Institute of Environmental Health Sciences and Award Nos. EPA RD83479801 and EPA RD83489401 from the Environmental Protection Agency. NR 30 TC 15 Z9 15 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2012 VL 5 IS 2 BP 197 EP U103 DI 10.1161/CIRCOUTCOMES.111.962456 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916RG UT WOS:000302120300013 PM 22354937 ER PT J AU Roe, MT White, JA Kaul, P Tricoci, P Lokhnygina, Y Miller, CD van't Hof, AW Montalescot, G James, SK Saucedo, J Ohman, EM Pollack, CV Hochman, JS Armstrong, PW Giugliano, RP Harrington, RA Van de Werf, F Califf, RM Newby, LK AF Roe, Matthew T. White, Jennifer A. Kaul, Padma Tricoci, Pierluigi Lokhnygina, Yuliya Miller, Chadwick D. van't Hof, Arnoud W. Montalescot, Gilles James, Stefan K. Saucedo, Jorge Ohman, E. Magnus Pollack, Charles V., Jr. Hochman, Judith S. Armstrong, Paul W. Giugliano, Robert P. Harrington, Robert A. Van de Werf, Frans Califf, Robert M. Newby, L. Kristin TI Regional Patterns of Use of a Medical Management Strategy for Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Insights From the EARLY ACS Trial SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE non-ST-segment elevation acute coronary syndrome; medical management; coronary artery disease; mortality ID UNSTABLE ANGINA; CARDIAC-CATHETERIZATION; MYOCARDIAL-INFARCTION; OUTCOMES; PREDICTORS; DEATH AB Background-Regional differences in the profile and prognosis of non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients treated with medical management after angiography remain uncertain. Methods and Results-Using data from the Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute Coronary Syndromes (EARLY ACS) trial, we examined regional variations in the use of an in-hospital medical management strategy in NSTE ACS patients who had significant coronary artery disease (CAD) identified during angiography, factors associated with the use of a medical management strategy, and 1-year mortality rates. Of 9406 patients, 8387 (89%) underwent angiography and had significant CAD; thereafter, 1766 (21%) were treated solely with a medical management strategy (range: 18% to 23% across 4 major geographic regions). Factors most strongly associated with a medical management strategy were negative baseline troponin values, prior coronary artery bypass grafting, lower baseline hemoglobin values, and greater number of diseased vessels; region was not a significant factor. One-year mortality was higher among patients treated with a medical management strategy compared with those who underwent revascularization (7.8% versus 3.6%; adjusted hazard ratio, 1.46; 95% CI, 1.21-1.76), with no significant interaction by region (interaction probability value=0.42). Conclusions-Approximately 20% of NSTE ACS patients with significant CAD in an international trial were treated solely with an in-hospital medical management strategy after early angiography, with no regional differences in factors associated with medical management or the risk of 1-year mortality. These findings have important implications for the conduct of future clinical trials, and highlight global similarities in the profile and prognosis of medically managed NSTE ACS patients. C1 [Roe, Matthew T.; White, Jennifer A.; Kaul, Padma; Lokhnygina, Yuliya; Ohman, E. Magnus; Harrington, Robert A.; Califf, Robert M.; Newby, L. Kristin] Duke Clin Res Inst, Durham, NC 27705 USA. [Kaul, Padma; Armstrong, Paul W.] Univ Alberta, Edmonton, AB, Canada. [Miller, Chadwick D.] Wake Forest Univ, Bowman Gray Sch Med, Dept Emergency Med, Winston Salem, NC USA. [van't Hof, Arnoud W.] Hosp Weezenlanden, Div Cardiol, Zwolle, Netherlands. [Montalescot, Gilles] Hop La Pitie Salpetriere, Inst Cardiol, Paris, France. [James, Stefan K.] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Saucedo, Jorge] Univ Oklahoma, Med Ctr, Div Cardiol, Oklahoma City, OK USA. [Pollack, Charles V., Jr.] Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. [Hochman, Judith S.] NYU, Sch Med, Dept Med, New York, NY USA. [Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Van de Werf, Frans] Gasthuisberg Univ Hosp Leuven, Dept Cardiovasc Dis, Louvain, Belgium. RP Roe, MT (reprint author), Duke Clin Res Inst, 2400 Pratt St,Room 7035, Durham, NC 27705 USA. EM matthew.roe@duke.edu OI Van de Werf, Frans/0000-0001-9479-7767; Hochman, Judith/0000-0002-5889-5981 FU Schering-Plough Corporation; Merck Co, Inc.; Merck; Schering-Plough/Merck; Schering-Plough FX The EARLY ACS trial was funded by Schering-Plough Corporation. These analyses were funded by research grant support from Merck & Co, Inc.; Dr Roe has received prior research support from Merck/Schering-Plough and compensation from Merck for clinical end point adjudication activities. Dr Tricoci has received advisory board and research support from Merck. Dr Miller has received research support from Schering-Plough/Merck. Dr van't Hof has received lecture fees and unrestricted grants from Schering Plough/Merck. Dr Montalescot has received consulting/lecture fees from Schering-Plough/Merck. Dr James has received research support and speaker fees from Schering-Plough. Dr Ohman is a principal investigator for Schering-Plough, now Merck. Dr Pollack has received research support from Schering-Plough. Dr Hochman is on the advisory board for Schering-Plough/Merck. Dr Armstrong has done consulting for Merck Frosst Canada Ltd. and receives research support from Schering-Plough/Merck. Dr Giugliano has received research support, advisory board, and honoraria for CME lectures from Schering-Plough/Merck. Dr Harrington has received research support and consulting with Schering-Plough/Merck. Dr Van de Werf has received research support, advisory board, and speaker fee from Schering-Plough/Merck. Dr Califf has received research funding and consulting with Schering-Plough, now Merck (all consulting funds donated to not-for-profits). Dr Saucedo has received research support, advisory board, and honoraria for lectures from Schering-Plough/Merck. Dr Newby has received research support from Schering-Plough/Merck. Ms White and Drs Lokhnygina and Kaul have no conflicts to disclose. NR 14 TC 15 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2012 VL 5 IS 2 BP 205 EP 213 DI 10.1161/CIRCOUTCOMES.111.962332 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916RG UT WOS:000302120300014 PM 22373905 ER PT J AU Afilalo, J Mottillo, S Eisenberg, MJ Alexander, KP Noiseux, N Perrault, LP Morin, JF Langlois, Y Ohayon, SM Monette, J Boivin, JF Shahian, DM Bergman, H AF Afilalo, Jonathan Mottillo, Salvatore Eisenberg, Mark J. Alexander, Karen P. Noiseux, Nicolas Perrault, Louis P. Morin, Jean-Francois Langlois, Yves Ohayon, Samuel M. Monette, Johanne Boivin, Jean-Francois Shahian, David M. Bergman, Howard TI Addition of Frailty and Disability to Cardiac Surgery Risk Scores Identifies Elderly Patients at High Risk of Mortality or Major Morbidity SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE cardiac surgery; outcomes; aging; frailty; disability; elderly; heart valve surgery ID LONG-TERM SURVIVAL; BYPASS-GRAFTING SURGERY; IN-HOSPITAL MORTALITY; OLDER-ADULTS; FUNCTIONAL STATUS; VALVE SURGERY; GAIT SPEED; MODELS; EUROSCORE; STRATIFICATION AB Background-Cardiac surgery risk scores perform poorly in elderly patients, in part because they do not take into account frailty and disability which are critical determinants of health status with advanced age. There is an unmet need to combine established cardiac surgery risk scores with measures of frailty and disability to provide a more complete model for risk prediction in elderly patients undergoing cardiac surgery. Methods and Results-This was a prospective, multicenter cohort study of elderly patients (>= 70 years) undergoing coronary artery bypass and/or valve surgery in the United States and Canada. Four different frailty scales, 3 disability scales, and 5 cardiac surgery risk scores were measured in all patients. The primary outcome was the STS composite end point of in-hospital postoperative mortality or major morbidity. A total of 152 patients were enrolled, with a mean age of 75.9+/-4.4 years and 34% women. Depending on the scale used, 20-46% of patients were found to be frail, and 5-76% were found to have at least 1 disability. The most predictive scale in each domain was: 5-meter gait speed >= 6 seconds as a measure of frailty (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.17-5.90), >= 3 impairments in the Nagi scale as a measure of disability (OR, 2.98; 95% CI, 1.35-6.56) and either the Parsonnet score (OR, 1.08; 95% CI, 1.04-1.13) or Society of Thoracic Surgeons Predicted Risk of Mortality or Major Morbidity (STS-PROMM) (OR, 1.05; 95% CI, 1.01-1.09) as a cardiac surgery risk score. Compared with the Parsonnet score or STS-PROMM alone, (area under the curve, 0.68-0.72), addition of frailty and disability provided incremental value and improved model discrimination (area under the curve, 0.73-0.76). Conclusions-Clinicians should use an integrative approach combining frailty, disability, and risk scores to better characterize elderly patients referred for cardiac surgery and identify those that are at increased risk. (Circ Cardiovasc Qual Outcomes. 2012;5:222-228.) C1 [Afilalo, Jonathan; Eisenberg, Mark J.] McGill Univ, SMBD Jewish Gen Hosp, Div Cardiol, Montreal, PQ H3T 1E2, Canada. [Afilalo, Jonathan; Mottillo, Salvatore; Eisenberg, Mark J.; Boivin, Jean-Francois] McGill Univ, SMBD Jewish Gen Hosp, Div Clin Epidemiol, Montreal, PQ H3T 1E2, Canada. [Morin, Jean-Francois; Langlois, Yves; Ohayon, Samuel M.] McGill Univ, SMBD Jewish Gen Hosp, Div Cardiac Surg, Montreal, PQ H3T 1E2, Canada. [Monette, Johanne; Bergman, Howard] McGill Univ, SMBD Jewish Gen Hosp, Div Geriatr Med, Montreal, PQ H3T 1E2, Canada. [Alexander, Karen P.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Noiseux, Nicolas] Univ Montreal, Ctr Hosp Univ Montreal, Ctr Rech, Div Cardiac Surg, Montreal, PQ, Canada. [Perrault, Louis P.] Univ Montreal, Montreal Heart Inst, Div Cardiac Surg, Montreal, PQ, Canada. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02115 USA. RP Afilalo, J (reprint author), McGill Univ, SMBD Jewish Gen Hosp, Div Cardiol, 3755 Cote Sainte Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM jonathan@afilalo.com FU Fonds de la Recherche en Sante du Quebec; Royal College of Physicians and Surgeons of Canada FX Dr Afilalo is supported by the Fonds de la Recherche en Sante du Quebec and the Royal College of Physicians and Surgeons of Canada Detweiller Grant. NR 47 TC 100 Z9 100 U1 1 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAR PY 2012 VL 5 IS 2 BP 222 EP U140 DI 10.1161/CIRCOUTCOMES.111.963157 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916RG UT WOS:000302120300016 PM 22396586 ER PT J AU Vivo, RP Krim, SR Krim, NR Zhao, X Hernandez, AF Peterson, ED Pina, IL Bhatt, DL Schwamm, LH Fonarow, GC AF Vivo, Rey P. Krim, Selim R. Krim, Nassim R. Zhao, Xin Hernandez, Adrian F. Peterson, Eric D. Pina, Ileana L. Bhatt, Deepak L. Schwamm, Lee H. Fonarow, Gregg C. TI Care and Outcomes of Hispanic Patients Admitted With Heart Failure With Preserved or Reduced Ejection Fraction Findings From Get With The Guidelines-Heart Failure SO CIRCULATION-HEART FAILURE LA English DT Article DE congestive heart failure; contractile function; health policy and outcome research ID ACUTE MYOCARDIAL-INFARCTION; NATIONAL REGISTRY ADHERE; QUALITY-OF-CARE; SYSTOLIC FUNCTION; INSULIN-RESISTANCE; ETHNIC-DIFFERENCES; RISK-FACTORS; OPTIMIZE-HF; AMERICANS; DISEASE AB ackground-Although individuals of Hispanic ethnicity are at high risk for developing heart failure (HF), little is known about differences between Hispanic HF patients stratified by left ventricular ejection fraction (EF). We compared characteristics, quality of care, and outcomes between Hispanic and non-Hispanic white patients hospitalized for HF with preserved EF (PEF) or reduced EF (REF). Methods and Results-From 247 hospitals in Get With The Guidelines-Heart Failure between 2005-2010, 6117 Hispanics were compared with 71 859 non-Hispanic whites. Forty-six percent of Hispanics had PEF (EF > 40%), whereas 54% had REF (EF <40%); 55% and 45% of non-Hispanic whites had PEF and REF, respectively. Relative to non-Hispanic whites, Hispanics with PEF or REF were more likely to be younger and to have diabetes, hypertension, and overweight/obesity. In multivariate analysis, a lower mortality risk was observed among Hispanics with PEF (odds ratio, 0.50; 95% confidence interval, 0.31-0.81; P=0.005) but not in Hispanics with REF (odds ratio, 0.94; 95% confidence interval, 0.62-1.43; P=0.784) compared with non-Hispanic whites. In all groups, composite performance improved within the study period (Hispanics PEF: 75.2-95.1%; non-Hispanic whites PEF: 79.0-92.7%; Hispanics REF: 67.7-88.4%; non-Hispanic whites REF: 60.8-85.6%, P<0.0001). Conclusions-Hispanic HF patients with PEF had better in-hospital survival than non-Hispanic whites with PEF. Inpatient mortality was similar between groups with REF. Quality of care was similar and improved over time irrespective of ethnicity, highlighting the potential benefit of performance improvement programs in promoting equitable care. (Circ Heart Fail. 2012; 5: 167-175.) C1 [Vivo, Rey P.] Univ Texas Galveston, Med Branch, Div Cardiol, Galveston, TX 77555 USA. [Vivo, Rey P.] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA. [Krim, Selim R.] Ochsner Heart & Vasc Inst, New Orleans, LA USA. [Krim, Nassim R.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Zhao, Xin; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Pina, Ileana L.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Pina, Ileana L.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. RP Vivo, RP (reprint author), Univ Texas Galveston, Med Branch, Div Cardiol, 301 Univ Blvd, Galveston, TX 77555 USA. EM rpvivo@gmail.com RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Council of Clinical Cardiology of the AHA; Medtronic; Ortho-McNeil; AHA Pharmaceutical Roundtable; GlaxoSmithKline; Johnson Johnson; Bristol-Meyers Squibb; Sanofi; Merck; Schering-Plough; Lilly; Amarin; Astra Zeneca; Eisai; Ethicon; Sanofi Aventis; National Heart, Lung, and Blood Institute; Medicines Company FX This study was supported in part by a Young Investigator database research seed grant from the Council of Clinical Cardiology of the AHA. The GWTG-HF program is provided by the AHA and is currently supported in part by Medtronic, Ortho-McNeil, and the AHA Pharmaceutical Roundtable. GWTG-HF has been funded in the past through support from GlaxoSmithKline.; Dr Hernandez reports receiving research grants from Johnson & Johnson and honoraria from Medtronic, Amgen, and Astra Zeneca. Dr Peterson serves as the Principal Investigator of the Data Analytic Center for the GWTG of the AHA. He reports receiving research support from Bristol-Meyers Squibb, Sanofi, Merck, Schering-Plough, Lilly, and Johnson & Johnson. Dr Bhatt reports receiving grants from Amarin, Astra Zeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company (significant); he serves as the Chair of the AHA GWTG Science Subcommittee. Dr Schwamm serves as Chair of the GWTG Steering Committee of the AHA. Dr Fonarow served as former Chair of the AHA GWTG Steering Committee. He reports receiving research grants from National Heart, Lung, and Blood Institute (significant); receiving honoraria from Medtronic (modest); and serving as a consultant for Novartis (significant). The remaining authors report no conflicts of interest. The authors are solely responsible for the design and conduct of this study, all analyses, and the drafting and editing of the article and its final contents. NR 29 TC 10 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAR PY 2012 VL 5 IS 2 BP 167 EP U118 DI 10.1161/CIRCHEARTFAILURE.111.963546 PG 25 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916RL UT WOS:000302120800016 PM 22414939 ER PT J AU Chae, CU Albert, CM Moorthy, MV Lee, IM Buring, JE AF Chae, Claudia U. Albert, Christine M. Moorthy, M. V. Lee, I-Min Buring, Julie E. TI Vitamin E Supplementation and the Risk of Heart Failure in Women SO CIRCULATION-HEART FAILURE LA English DT Article DE antioxidants; epidemiology; heart failure; prevention; women ID RANDOMIZED CONTROLLED-TRIAL; PRESERVED EJECTION FRACTION; LOW-DOSE ASPIRIN; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION; VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; DIAGNOSTIC-CRITERIA; HEALTH AB Background-Oxidative stress may contribute to the development of heart failure (HF); however, an increased risk of HF has been observed with antioxidant therapy in secondary prevention trials. No large clinical trials have addressed the role of antioxidant therapy in the primary prevention of HF. Methods and Results-We examined the effect of vitamin E and HF risk in 39 815 initially healthy women, aged at least 45 years at baseline, who were enrolled in the Women's Health Study, a randomized, double-blind, placebo-controlled trial of vitamin E (600 IU every other day). Over a median follow-up of 10.2 years, there were 220 incident HF events. In proportional hazards models, adjusting for age and randomized aspirin and beta carotene treatment, vitamin E assignment did not significantly affect HF risk (hazards ratio [HR], 0.93; 95% CI, 0.71-1.21; P=0.59). These results did not change with multivariate adjustment for other risk factors, including interim myocardial infarction. In a prespecified subgroup analysis, vitamin E was inversely related to developing HF with normal ejection fraction (>= 50%) with HR 0.59 (95% CI, 0.38-0.92; P=0.02), but there was no statistically significant effect on the risk of developing systolic HF (HR, 1.26; 95% CI, 0.84-1.89; P=0.26). Conclusions-In this population of apparently healthy women, vitamin E did not affect the overall risk of HF. The possible benefit on diastolic HF requires confirmation in larger populations. C1 [Chae, Claudia U.] Massachusetts Gen Hosp, Div Cardiol, YAW 5800, Boston, MA 02114 USA. [Chae, Claudia U.; Albert, Christine M.; Moorthy, M. V.; Lee, I-Min; Buring, Julie E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Albert, Christine M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Arrhythmia Prevent, Boston, MA 02115 USA. [Albert, Christine M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Lee, I-Min; Buring, Julie E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Chae, CU (reprint author), Massachusetts Gen Hosp, Div Cardiol, YAW 5800, 55 Fruit St, Boston, MA 02114 USA. EM cchae@partners.org FU Massachusetts General Hospital; Donald W. Reynolds Foundation; National Heart, Lung, and Blood Institute [HL-043851, HL-080467]; National Cancer Institute [CA-047988] FX This work was supported by the Elizabeth Anne and Karen Barlow Corrigan Women's Heart Health Program at Massachusetts General Hospital, the Donald W. Reynolds Foundation, and grants HL-043851 and HL-080467 from the National Heart, Lung, and Blood Institute and CA-047988 from the National Cancer Institute. NR 37 TC 9 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAR PY 2012 VL 5 IS 2 BP 176 EP 182 DI 10.1161/CIRCHEARTFAILURE.111.963793 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916RL UT WOS:000302120800017 PM 22438520 ER PT J AU Rector, TS Carson, PE Anand, IS McMurray, JJ Zile, MR McKelvie, RS Komajda, M Kuskowski, M Massie, BM AF Rector, Thomas S. Carson, Peter E. Anand, Inder S. McMurray, John J. Zile, Michael R. McKelvie, Robert S. Komajda, Michel Kuskowski, Michael Massie, Barry M. CA I-PRESERVE Trial Investigators TI Assessment of Long-Term Effects of Irbesartan on Heart Failure With Preserved Ejection Fraction as Measured by the Minnesota Living With Heart Failure Questionnaire in the Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) Trial SO CIRCULATION-HEART FAILURE LA English DT Article DE diastolic heart failure; ARBs; quality of life ID QUALITY-OF-LIFE; CLINICAL CHARACTERISTICS; RANDOMIZED-TRIAL; DOUBLE-BLIND; DYSFUNCTION; PLACEBO; RELIABILITY; PREVALENCE; VALIDITY AB Background-The Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used in a large, multinational, randomized, placebo-controlled trial to measure adverse effects of heart failure with preserved ejection fraction (HF-PEF) on patients' lives and the effects of irbesartan. Methods and Results-Patients with symptomatic HF-PEF were randomly assigned to irbesartan (up to 300 mg daily) or placebo. The MLHFQ was administered at baseline (n=3605), month 6 (n=3137), month 14 (n=2904), and the end of study (median, 56 months, n=2205). Baseline MLHFQ scores of 43 +/- 21 indicated that HF-PEF had a substantial adverse effects. Estimated retest reliability was 0.80. Baseline MLHFQ scores were associated with other measures of the severity of heart failure including symptoms, signs of congestion, cardiac structure, and time to hospitalizations or deaths attributed to heart failure. Slight improvement in shortness of breath or fatigue was associated with significant improvement in MLHFQ scores (-5.9 and -5.0, P<0.0001). Compared with placebo, further improvement in MLHFQ scores was not observed with irbesartan after 6 months (mean adjusted difference, 0.4; 95% confidence interval, -0.8 to 1.7), 14 months (0.5; 95% confidence interval, -0.9 to 1.8), or the end of study (2.0; 95% confidence interval, -4.1 to 0.01). Conclusions-The MLHFQ scores are a reliable, valid, and sensitive measure of the adverse impact of HF-PEF on patients' lives. Irbesartan did not substantially improve MLHFQ scores during a long period of follow-up. C1 [Rector, Thomas S.; Anand, Inder S.] Univ Minnesota, Dept Vet Affairs Hlth Care Syst, Minneapolis, MN USA. [Rector, Thomas S.; Anand, Inder S.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Carson, Peter E.] Dept Vet Affairs Hlth Care Syst, Washington, DC USA. [Carson, Peter E.] Georgetown Univ Hosp, Washington, DC 20007 USA. [McMurray, John J.] Univ Glasgow, British Heart Fdn, Cardiovasc Res Ctr, Glasgow G12 8QQ, Lanark, Scotland. [Zile, Michael R.] Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. [Zile, Michael R.] Med Univ S Carolina, Charleston, SC 29425 USA. [McKelvie, Robert S.] Populat Hlth Res Inst, Hamilton, ON, Canada. [McKelvie, Robert S.] McMaster Univ, Hamilton, ON, Canada. [Kuskowski, Michael] Hop La Pitie Salpetriere, Dept Cardiol, Paris, France. [Komajda, Michel] Univ Paris 06, Paris, France. [Komajda, Michel] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Massie, Barry M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.] San Francisco Dept Vet Affairs Hlth Care Syst, San Francisco, CA USA. RP Rector, TS (reprint author), Minneapolis VA Hlth Care Syst, 1 Vet Dr, Minneapolis, MN 55417 USA. EM thomas.rector@va.gov FU Bristol-Myers Squibb; Sanofi-Aventis; Veterans Health Administration [HFP-98-001]; Servier FX The I-PRESERVE Trial was funded by Bristol-Myers Squibb and Sanofi-Aventis. Dr Rector was supported by the Veterans Health Administration [Health Services Research and Development grant HFP-98-001. All expressed views and conclusions are the authors' and do not necessarily represent the Veterans Health Administration.; Drs Anand, Carson, and Zile received consulting fees from Bristol-Myers Squibb and/or Sanofi-Aventis. Dr McMurray received support from Bristol-Myers Squibb (to Glasgow University) for his work on this trial. Dr Komajda received consulting fees from Bristol-Myers Squibb and Servier and lecture fees from Sanofi-Aventis. Dr McKelvie received consulting fees and lecture fees from Bristol-Myers Squibb and Sanofi-Aventis. Dr Massie received grant support and consulting fees from Bristol-Myers Squibb and Sanofi-Aventis. Drs Rector and Kuskowski have no industry relationships to disclose. Dr Rector receives royalty payments from the University of Minnesota for licensed use of the Minnesota Living with Heart Failure Questionnaire. NR 24 TC 16 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAR PY 2012 VL 5 IS 2 BP 217 EP 225 DI 10.1161/CIRCHEARTFAILURE.111.964221 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916RL UT WOS:000302120800022 PM 22267751 ER PT J AU Singh, TP Almond, CS Semigran, MJ Piercey, G Gauvreau, K AF Singh, Tajinder P. Almond, Christopher S. Semigran, Marc J. Piercey, Gary Gauvreau, Kimberlee TI Risk Prediction for Early In-Hospital Mortality Following Heart Transplantation in the United States SO CIRCULATION-HEART FAILURE LA English DT Article DE transplantation; survival; risk factors; decision support techniques; heart failure ID GLOMERULAR-FILTRATION-RATE; VENTRICULAR ASSIST DEVICE; GLOBAL CARDIOVASCULAR RISK; SERUM CREATININE VALUES; INTERNATIONAL SOCIETY; LUNG TRANSPLANTATION; RENAL-DISEASE; VALIDATION; EQUATION; SURVIVAL AB Background-Risk factors for early mortality after heart transplant (HT) have not been used for quantitative risk prediction. We sought to develop and validate a risk prediction model for posttransplant in-hospital mortality in HT recipients. Methods and Results-We derived the model in subjects aged >= 18 years who underwent primary HT in the United States from January 2007 to June 2009 (n=4248) and validated it internally using a bootstrapping technique (200 random samples, n=4248). We then assessed the model's performance in patients receiving an HT from July 2009 to October 2010 (external validation cohort, n=2346). Posttransplant in-hospital mortality was 4.7% in the model derivation cohort. The best-fitting model based on recipient characteristics at transplant had 6 variables: age, diagnosis, type of mechanical support, ventilator support, estimated glomerular filtration rate, and total serum bilirubin. Model discrimination for survivors versus nonsurvivors was acceptable during derivation and internal validation (C statistic, 0.722 and 0.731, respectively) as was model calibration during derivation (Hosmer Lemeshow [HL] P=0.47). Model performance was reasonable in the external validation cohort (predicted mortality, 4.9%; actual mortality, 4.3%; R-2=0.95; C statistic, 0.68; HL P=0.48). Adding the donor-related variables of age and ischemic time to the model improved its performance in both the model derivation (C statistic, 0.742; HL P=0.70) and the external validation (C statistic, 0.695; HL P=0.42) cohorts. Conclusions-The proposed model allows risk stratification of HT candidates for early posttransplant mortality and may be useful in counseling patients with regard to their posttransplant prognosis. The model with additional donor-related variables may be useful during donor selection. (Circ Heart Fail. 2012;5:259-266.) C1 [Singh, Tajinder P.; Almond, Christopher S.; Piercey, Gary; Gauvreau, Kimberlee] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. [Semigran, Marc J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Singh, Tajinder P.; Almond, Christopher S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Semigran, Marc J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gauvreau, Kimberlee] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Singh, TP (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. EM TP.Singh@cardio.chboston.org FU Department of Cardiology, Children's Hospital Boston, Boston, Massachusetts; Health Resources and Services Administration [234-2005-370011C] FX This study was supported by the Heart Transplant Research and Education Fund, Department of Cardiology, Children's Hospital Boston, Boston, Massachusetts, and in part by Health Resources and Services Administration contract 234-2005-370011C. NR 30 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-3289 J9 CIRC-HEART FAIL JI Circ.-Heart Fail. PD MAR PY 2012 VL 5 IS 2 BP 259 EP U239 DI 10.1161/CIRCHEARTFAILURE.111.965996 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916RL UT WOS:000302120800027 PM 22308287 ER PT J AU Karaosmanoglu, AD Blake, MA AF Karaosmanoglu, Ali Devrim Blake, Michael A. TI Applications of PET-CT in patients with esophageal cancer SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Review DE PET scan; cancer; esophagus ID POSITRON-EMISSION-TOMOGRAPHY; SQUAMOUS-CELL CARCINOMA; ECTOPIC GASTRIC-MUCOSA; ESOPHAGOGASTRIC JUNCTION; BARRETTS-ESOPHAGUS; RISK-FACTORS; TUMOR RESPONSE; LYMPH-NODES; FDG PET; ADENOCARCINOMA AB Although esophageal cancer is not among the common cancers as prostate, lung, breast, or colon malignancies, it has an exceedingly high mortality rate, with its incidence close to the cancer-specific mortality. Currently, the only potentially curative treatment is surgery. Unfortunately, surgical treatment is extensive and may have significant morbidity and mortality related with it. Given these facts, selection of patients who are amenable to surgical treatment is of utmost importance. Conventional morphology based cross-sectional imaging modalities are extremely helpful for pre-surgical evaluation and follow-up of these patients, however, they have very well-known limitations. Positron emission tomography-computed tomography (PET-CT) is a relatively new, highly promising molecular imaging technique which may overcome some of the fundemental limitations of these conventional cross-sectional modalities in the pre-surgical evaluation and follow-up of these patients. In this review, we evaluated the applications of PET-CT in patients with esophageal cancer. C1 [Karaosmanoglu, Ali Devrim] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02115 USA. RP Karaosmanoglu, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Abdominal Imaging & Intervent Radiol, Boston, MA 02115 USA. EM alidevrim76@yahoo.com RI Karaosmanoglu, Ali/D-8624-2015 OI Karaosmanoglu, Ali/0000-0003-0027-9593 NR 48 TC 8 Z9 8 U1 0 U2 4 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD MAR-APR PY 2012 VL 18 IS 2 BP 171 EP 182 DI 10.4261/1305-3825.DIR.4309-11.1 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 917VI UT WOS:000302206300006 PM 22198910 ER PT J AU Abbott, AL Adelman, MA Alexandrov, AV Barnett, HJM Beard, J Bell, P Bjorck, M Blacker, D Buckley, CJ Cambria, RP Comerota, AJ Connolly, ES Davies, AH Eckstein, HH Faruqi, R Fraedrich, G Gloviczki, P Hankey, GJ Harbaugh, RE Heldenberg, E Kittner, SJ Kleinig, TJ Mikhailidis, DP Moore, WS Naylor, R Nicolaides, A Paraskevas, KI Pelz, DM Prichard, JW Purdie, G Ricco, JB Riles, T Rothwell, P Sandercock, P Sillesen, H Spence, JD Spinelli, F Tan, A Thapar, A Veith, FJ Zhou, W AF Abbott, A. L. Adelman, M. A. Alexandrov, A. V. Barnett, H. J. M. Beard, J. Bell, P. Bjorck, M. Blacker, D. Buckley, C. J. Cambria, R. P. Comerota, A. J. Connolly, E. S., Jr. Davies, A. H. Eckstein, H. H. Faruqi, R. Fraedrich, G. Gloviczki, P. Hankey, G. J. Harbaugh, R. E. Heldenberg, E. Kittner, S. J. Kleinig, T. J. Mikhailidis, D. P. Moore, W. S. Naylor, R. Nicolaides, A. Paraskevas, K. I. Pelz, D. M. Prichard, J. W. Purdie, G. Ricco, J. B. Riles, T. Rothwell, P. Sandercock, P. Sillesen, H. Spence, J. D. Spinelli, F. Tan, A. Thapar, A. Veith, F. J. Zhou, W. TI Why the United States Center for Medicare and Medicaid Services (CMS) Should not Extend Reimbursement Indications for Carotid Artery Angioplasty/Stenting SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Letter ID RANDOMIZED CONTROLLED-TRIAL; STROKE PREVENTION; ENDARTERECTOMY; STENOSIS; RISK; REVASCULARIZATION; PROFESSIONALS; ASSOCIATION; GUIDELINES; THERAPY C1 [Abbott, A. L.] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia. [Abbott, A. L.] Florey Neurosci Inst, Melbourne, Vic, Australia. [Adelman, M. A.] NYU, Langone Med Ctr, New York, NY 10003 USA. [Alexandrov, A. V.] Univ Alabama Hosp & Clin, Birmingham, AL USA. [Barnett, H. J. M.] Univ Western Ontario, Robarts Res Inst, Toronto, ON, Canada. [Beard, J.] No Gen Hosp, Sheffield Vasc Inst, Sheffield S5 7AU, S Yorkshire, England. [Bell, P.] Univ Leicester, Leicester, Leics, England. [Bell, P.] Univ Leicester Hosp, Leicester, Leics, England. [Bjorck, M.] Uppsala Univ, Uppsala, Sweden. [Blacker, D.] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia. [Cambria, R. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cambria, R. P.] Harvard Univ, Sch Med, Boston, MA USA. [Comerota, A. J.] Toledo Hosp, Jobst Vasc Inst, Toledo, OH USA. [Connolly, E. S., Jr.] Columbia Univ, New York, NY 10027 USA. [Davies, A. H.] Charing Cross Hosp, Imperial Coll Sch Med, London, England. [Eckstein, H. H.] Tech Univ Munich, Klinikum Rechts Isar, D-8000 Munich, Germany. [Faruqi, R.] Stanford Univ, Kaiser Permanente Med Ctr, Stanford, CA 94305 USA. [Fraedrich, G.] Med Univ, Innsbruck, Austria. [Gloviczki, P.] Mayo Clin, Rochester, MN USA. [Hankey, G. J.] Royal Perth Hosp, Perth, WA, Australia. [Harbaugh, R. E.] Penn State Univ, Penn State Inst Neurosci, Hershey, PA USA. [Heldenberg, E.] Assaf Harofeh Med Ctr, IL-70300 Zerifin, Israel. [Kittner, S. J.] Univ Maryland, Sch Med, Baltimore, MD USA. [Kleinig, T. J.] Univ Adelaide, Royal Adelaide Hosp, Adelaide, SA, Australia. [Kittner, S. J.; Tan, A.] Univ Adelaide, Lyell McEwin Hosp, Adelaide, SA, Australia. [Mikhailidis, D. P.] UCL, Sch Med, London W1N 8AA, England. [Moore, W. S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Naylor, R.] Leicester Royal Infirm, Leicester, Leics, England. [Nicolaides, A.] Univ London Imperial Coll Sci Technol & Med, Vasc Diagnost Ctr, London, England. [Paraskevas, K. I.] Klinikum Nurnberg Sud, Nurnberg, Germany. [Pelz, D. M.] Univ Western Ontario, London, ON, Canada. [Prichard, J. W.] Yale Med Sch, New Haven, CT USA. [Purdie, G.; Tan, A.] Queen Elizabeth Hosp, Adelaide, SA, Australia. [Ricco, J. B.] Univ Poitiers, Poitiers, France. [Rothwell, P.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England. [Sandercock, P.] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. [Sillesen, H.] Univ Copenhagen, DK-1168 Copenhagen, Denmark. [Spence, J. D.] Univ Western Ontario, Robarts Res Inst, London, ON, Canada. [Spinelli, F.] Univ Messina, Messina, Italy. [Zhou, W.] Stanford Univ, Palo Alto VA Hlth Care Syst, Stanford, CA 94305 USA. [Veith, F. J.] NYU, Sch Med, Cleveland Clin, New York, NY 10003 USA. [Veith, F. J.] Case Western Reserve Univ, Lerner Sch Med, Cleveland, OH 44106 USA. RP Abbott, AL (reprint author), Baker IDI Heart & Diabet Inst, 75 Commercial Rd, Melbourne, Vic 3004, Australia. EM Annet.L.Abbott@gmail.com.au; Mark.Adelman@nyumc.org; avalexandrov@att.net; hjmb@bell.net; j.d.beard@btinternet.com; peterrfbell@googlemail.com; martin@bjorck.pp.se; David.Blacker@health.wa.gov.au; Clifford.Buckley@VA.GOV; RCAMBRIA@PARTNERS.ORG; anthony.comerotamd@promedica.org; esc5@columbia.edu; a.h.davies@imperial.ac.uk; HHEckstein@web.de; Rishad.Faruqi@kp.org; gustav.fraedrich@i-med.ac.at; gloviczki.peter@mayo.edu; gjhankey@cyllene.uwa.edu.au; rharbaugh@psu.edu; eitanh@asaf.health.gov.il; skittner@umaryland.edu; tkleinig@hotmail.com; MIKHAILIDIS@aol.com; WMoore@mednet.ucla.edu; ross.naylor@uhl-tr.nhs.uk; anicolaides1@gmail.com; paraskevask@hotmail.com; Pelz@uwo.ca; james.prichard@yale.edu; Grant.Purdie@health.sa.gov.au; jeanbaptistericco@gmail.com; Thomas.Riles@nyumc.org; peter.rothwell@clneuro.ox.ac.uk; Peter.sandercock@ed.ac.uk; sillesen@mac.com; dspence@robarts.ca; f.spinelli@mac.com; Aaron.Tan@health.sa.gov.au; a.thapar09@imperial.ac.uk; fjvmd@msn.com; weizhou@stanford.edu RI Mikhailidis, Dimitri/A-1869-2013; Bjorck, Martin/A-4104-2008; Hankey, Graeme /H-4968-2014; Spence, J. David/K-6396-2013; OI Hankey, Graeme /0000-0002-6044-7328; Spence, J. David/0000-0001-7478-1098; Spinelli, Francesco/0000-0001-6527-1993; Alexandrov, Andrei V/0000-0001-8871-1023; Adelman, Mark/0000-0001-9276-6131 FU The Dunhill Medical Trust [RCS/DMT 3RD ROUND (3)] NR 57 TC 12 Z9 12 U1 0 U2 8 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD MAR PY 2012 VL 43 IS 3 BP 247 EP 251 DI 10.1016/j.ejvs.2011.12.006 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 917SY UT WOS:000302200100001 PM 22226698 ER PT J AU Beck, D Niessner, H Kulms, D Flaherty, K Schaller, M Garbe, C Meier, F AF Beck, D. Niessner, H. Kulms, D. Flaherty, K. Schaller, M. Garbe, C. Meier, F. TI The BRAFV600E kinase inhibitor vemurafenib induces apoptosis through a process involving induction of endoplasmic reticulum stress in melanoma cells SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung (ADF) CY MAR 01-03, 2012 CL Marburg, GERMANY SP Arbeitsgemeinsch Dermatol Forsch (ADF) C1 [Beck, D.; Niessner, H.; Schaller, M.; Garbe, C.; Meier, F.] Univ Tubingen, Dept Dermatol, Tubingen, Germany. [Kulms, D.] Univ Stuttgart, Inst Cell Biol & Immunol, Stuttgart, Germany. [Flaherty, K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RI Kulms, Dagmar/H-1653-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2012 VL 21 IS 3 BP e12 EP e12 PG 1 WC Dermatology SC Dermatology GA 900ZP UT WOS:000300931700068 ER PT J AU Eberle, FC Song, JY Xi, L Raffeld, M Harris, NL Wilson, WH Pittaluga, S Jaffe, ES AF Eberle, F. C. Song, J. Y. Xi, L. Raffeld, M. Harris, N. L. Wilson, W. H. Pittaluga, S. Jaffe, E. S. TI Transformed cutaneous CD30 positive T-cell lymphoma of the lymph node mimicking classical Hodgkin lymphoma SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting of the Arbeitsgemeinschaft-Dermatologische-Forschung (ADF) CY MAR 01-03, 2012 CL Marburg, GERMANY SP Arbeitsgemeinsch Dermatol Forsch (ADF) C1 [Eberle, F. C.] Univ Tubingen, Dept Dermatol, D-72074 Tubingen, Germany. [Eberle, F. C.; Song, J. Y.; Xi, L.; Raffeld, M.; Pittaluga, S.; Jaffe, E. S.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Harris, N. L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Harris, N. L.] Harvard Univ, Sch Med, Boston, MA USA. [Wilson, W. H.] NCI, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2012 VL 21 IS 3 BP e19 EP e20 PG 2 WC Dermatology SC Dermatology GA 900ZP UT WOS:000300931700114 ER PT J AU Yoon, WJ Brugge, WR AF Yoon, Won Jae Brugge, William R. TI Pancreatic Cystic Neoplasms: Diagnosis and Management SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Pancreatic cystic neoplasm; Intraductal papillary mucinous neoplasm; Mucinous cystic neoplasm; Serous cystic neoplasm; Solid-pseudopapillary neoplasm ID PAPILLARY MUCINOUS NEOPLASMS; FINE-NEEDLE-ASPIRATION; SOLID PSEUDOPAPILLARY NEOPLASM; OPTICAL COHERENCE TOMOGRAPHY; OVARIAN-TYPE STROMA; SEROUS-CYSTADENOMA; CLINICOPATHOLOGICAL FEATURES; PATHOLOGICAL CORRELATION; DIFFERENTIAL-DIAGNOSIS; ENDOSCOPIC ULTRASOUND AB Pancreatic cystic neoplasms are detected with increasing frequency. The management of such lesions is frequently hampered by limitations of current imaging techniques, difficulty in tissue acquisition, and the morbidity and mortality associated with pancreatic resection. Despite recent development in our understanding of the premalignant nature of mucinous lesions, the indications and timing of surgery remain controversial. More effort is needed to improve our diagnostic and treatment ability of pancreatic cystic neoplasms. C1 [Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Yoon, Won Jae] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. EM wbrugge@partners.org NR 100 TC 22 Z9 25 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 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 2012 VL 41 IS 1 BP 103 EP + DI 10.1016/j.gtc.2011.12.016 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 914YH UT WOS:000301989100008 PM 22341252 ER PT J AU Halperin, DM Kulke, MH AF Halperin, Daniel M. Kulke, Matthew H. TI Management of Pancreatic Neuroendocrine Tumors SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Neuroendocrine tumor; Pancreatic neuroendocrine tumor; Islet cell tumor; Diagnosis; Prognosis; Management ID ZOLLINGER-ELLISON-SYNDROME; ISLET-CELL-CARCINOMA; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; DUODX AFFECT RATE; PHASE-II; LIVER METASTASES; ENDOCRINE TUMOR; CUSHINGS-SYNDROME; CHROMOGRANIN-A; INSULINOMA AB Pancreatic neuroendocrine tumors secrete hormones that can result in characteristic clinical syndromes; however, most remain clinically silent and are diagnosed at a late stage. Tumor stage and histologic grade are associated with prognosis and help guide therapeutic decisions. Surgical resection is generally attempted in patients with localized disease. In patients with surgically unresectable disease, treatment with somatostatin analogs, hepatic embolization, or cytotoxic chemotherapy may be recommended. Newer targeted therapies have been shown to improve progression-free survival durations and were recently approved for use in patients with advanced pancreatic neuroendocrine tumors, further expanding treatment options for patients with this disease. C1 [Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Carcinoid & Pancreat Neuroendocrine Tumor Program, Boston, MA 02115 USA. [Halperin, Daniel M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kulke, Matthew H.] Harvard Univ, Sch Med, Boston, MA USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Carcinoid & Pancreat Neuroendocrine Tumor Program, 44 Binney St, Boston, MA 02115 USA. EM Matthew_Kulke@dfci.harvard.edu RI Halperin, Daniel M/I-1944-2013 OI Halperin, Daniel M/0000-0002-3113-930X NR 68 TC 6 Z9 6 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 EI 1558-1942 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 2012 VL 41 IS 1 BP 119 EP + DI 10.1016/j.gtc.2011.12.003 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 914YH UT WOS:000301989100009 PM 22341253 ER PT J AU Doi, H Iyer, TK Carpenter, E Li, H Chang, KM Vonderheide, RH Kaplan, DE AF Doi, Hiroyoshi Iyer, Tara K. Carpenter, Erica Li, Hong Chang, Kyong-Mi Vonderheide, Robert H. Kaplan, David E. TI Dysfunctional B-cell activation in cirrhosis resulting from hepatitis C infection associated with disappearance of CD27-Positive B-cell population SO HEPATOLOGY LA English DT Article ID SOLUBLE CD14; VIRUS-INFECTION; MICROBIAL TRANSLOCATION; LIVER-TRANSPLANTATION; IMMUNE ACTIVATION; LYMPHOCYTES; EXPRESSION; SERUM; INDIVIDUALS; COMPARTMENT AB Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis and hepatocellular carcinoma (HCC). Both advanced solid tumors and HCV have previously been associated with memory B-cell dysfunction. In this study, we sought to dissect the effect of viral infection, cirrhosis, and liver cancer on memory B-cell frequency and function in the spectrum of HCV disease. Peripheral blood from healthy donors, HCV-infected patients with F1-F2 liver fibrosis, HCV-infected patients with cirrhosis, patients with HCV-related HCC, and non-HCV-infected cirrhotics were assessed for B-cell phenotype by flow cytometry. Isolated B cells were stimulated with anticluster of differentiation (CD)40 antibodies and Toll-like receptor (TLR)9 agonist for assessment of costimulation marker expression, cytokine production, immunoglobulin (Ig) production, and CD4+ T-cell allostimulatory capacity. CD27+ memory B cells and, more specifically, CD27+IgM+ B cells were markedly less frequent in cirrhotic patients independent of HCV infection. Circulating B cells in cirrhotics were hyporesponsive to CD40/TLR9 activation, as characterized by CD70 up-regulation, tumor necrosis factor beta secretion, IgG production, and T-cell allostimulation. Last, blockade of TLR4 and TLR9 signaling abrogated the activation of healthy donor B cells by cirrhotic plasma, suggesting a role for bacterial translocation in driving B-cell changes in cirrhosis. Conclusion: Profound abnormalities in B-cell phenotype and function occur in cirrhosis independent of HCV infection. These B-cell defects may explain, in part, the vaccine hyporesponsiveness and susceptibility to bacterial infection in this population. (HEPATOLOGY 2012) C1 [Chang, Kyong-Mi; Kaplan, David E.] Philadelphia VA Med Ctr, Med & Res Serv, Philadelphia, PA 19104 USA. [Doi, Hiroyoshi; Iyer, Tara K.; Li, Hong; Chang, Kyong-Mi; Kaplan, David E.] Univ Penn, Div Gastroenterol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Carpenter, Erica; Vonderheide, Robert H.] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Vonderheide, Robert H.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Vonderheide, Robert H.] Univ Penn, Div Hematol Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Kaplan, DE (reprint author), Philadelphia VA Med Ctr, Med & Res Serv, Res Bldg 21,A402A,3900 Woodland Ave, Philadelphia, PA 19104 USA. EM dakaplan@mail.med.upenn.edu OI Kaplan, David E./0000-0002-3839-336X FU NCI NIH HHS [R21 CA149908, R21 CA149908-01, T32 CA009140]; NIAAA NIH HHS [AA12849, R01 AA012849, R01 AA012849-05]; NIAID NIH HHS [AI47519, R01 AI047519, R01 AI047519-12]; NIDDK NIH HHS [L30 DK069063, L30 DK069063-01, P30 DK050306, P30 DK050306-15, P30-DK050306] NR 45 TC 21 Z9 22 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2012 VL 55 IS 3 BP 709 EP 719 DI 10.1002/hep.24689 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 897YS UT WOS:000300699900008 PM 21932384 ER PT J AU Rosen, RC Marx, BP Maserejian, NN Holowka, DW Gates, MA Sleeper, LA Vasterling, JJ Kang, HK Keane, TM AF Rosen, Raymond C. Marx, Brian P. Maserejian, Nancy N. Holowka, Darren W. Gates, Margaret A. Sleeper, Lynn A. Vasterling, Jennifer J. Kang, Han K. Keane, Terence M. TI Project VALOR: design and methods of a longitudinal registry of post-traumatic stress disorder (PTSD) in combat-exposed Veterans in the Afghanistan and Iraqi military theaters of operations SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH LA English DT Article DE post-traumatic stress disorder (PTSD); study design; disease registry; combat-exposed Veterans; psychosocial outcomes ID TRAUMATIC BRAIN-INJURY; STRUCTURED CLINICAL INTERVIEW; HARMFUL ALCOHOL-CONSUMPTION; MENTAL-HEALTH PROBLEMS; WAR VETERANS; PRIMARY-CARE; LIFE EVENTS; DEPLOYMENT; SYMPTOMS; THERAPY AB Few studies have investigated the natural history of post-traumatic stress disorder (PTSD). Project VALOR (Veterans' After-discharge Longitudinal Registry) was designed as a longitudinal patient registry assessing the course of combat-related PTSD among 1600 male and female Veterans who served in Operation Enduring Freedom (OEF) in Afghanistan or Operation Iraqi Freedom (OIF). Aims of the study include investigating patterns and predictors of progression or remission of PTSD and treatment utilization. The study design was based on recommendations from the Agency for Healthcare Quality and Research for longitudinal disease registries and used a pre-specified theoretical model to select the measurement domains for data collection and interpretation of forthcoming results. The registry will include 1200 male and female Veterans with a recent diagnosis of PTSD in the Department of Veteran Affairs (VA) electronic medical record and a comparison group of 400 Veterans without a medical record-based PTSD diagnosis, to also allow for case-control analyses. Data are collected from administrative databases, electronic medical records, a self-administered questionnaire, and a semi-structured diagnostic telephone interview. Project VALOR is a unique and timely registry study that will evaluate the clinical course of PTSD, psychosocial correlates, and health outcomes in a carefully selected cohort of returning OEF/OIF Veterans. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Rosen, Raymond C.; Maserejian, Nancy N.; Gates, Margaret A.; Sleeper, Lynn A.] New England Res Inst Inc, Watertown, MA 02472 USA. [Marx, Brian P.; Holowka, Darren W.; Vasterling, Jennifer J.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Marx, Brian P.; Holowka, Darren W.; Vasterling, Jennifer J.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Kang, Han K.] Environm Epidemiol Serv, Dept Vet Affairs, Washington, DC USA. RP Rosen, RC (reprint author), New England Res Inst Inc, 9 Galen St, Watertown, MA 02472 USA. EM rrosen@neriscience.com RI Schueter, nicos/A-3625-2014 FU US Department of Defense [W81XWH-08-2-0102, W81XWH-08-2-0100] FX This work was funded by the US Department of Defense Awards W81XWH-08-2-0102 and W81XWH-08-2-0100. NR 44 TC 13 Z9 13 U1 3 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1049-8931 J9 INT J METH PSYCH RES JI Int. J. Methods Psychiatr. Res. PD MAR PY 2012 VL 21 IS 1 BP 5 EP 16 DI 10.1002/mpr.355 PG 12 WC Psychiatry SC Psychiatry GA 907QI UT WOS:000301432000004 PM 22095917 ER PT J AU Maes, C Araldi, E Haigh, K Khatri, R Van Looveren, R Giaccia, AJ Haigh, JJ Carmeliet, G Schipani, E AF Maes, Christa Araldi, Elisa Haigh, Katharina Khatri, Richa Van Looveren, Riet Giaccia, Amato J. Haigh, Jody J. Carmeliet, Geert Schipani, Ernestina TI VEGF-independent cell-autonomous functions of HIF-1a regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ENDOCHONDRAL OSSIFICATION; CARTILAGE; CHONDROCYTE SURVIVAL; HYPOXIA; HIF ID HYPOXIA-INDUCIBLE FACTOR-1; ENDOTHELIAL GROWTH-FACTOR; ENDOCHONDRAL BONE-FORMATION; GENE-EXPRESSION; EPIPHYSEAL CHONDROCYTES; DIFFERENTIAL ROLES; O-2 HOMEOSTASIS; MULTIPLE ROLES; HIF-1-ALPHA; ANGIOGENESIS AB Fetal growth plate cartilage is nonvascularized, and chondrocytes largely develop in hypoxic conditions. We previously found that mice lacking the hypoxia-inducible transcription factor HIF-1a in cartilage show massive death of centrally located, hypoxic chondrocytes. A similar phenotype was observed in mice with genetic ablation of either all or specifically the diffusible isoforms of vascular endothelial growth factor (VEGF), a prime angiogenic target of HIF-1a. Here, we assessed whether VEGF is a critical downstream component of the HIF-1adependent survival pathway in chondrocytes. We used a genetic approach to conditionally overexpress VEGF164 in chondrocytes lacking HIF-1a, evaluating potential rescuing effects. The effectiveness of the strategy was validated by showing that transgenic expression of VEGF164 in Col2-Cre;VEGFf/f mice stimulated angiogenesis in the perichondrium, fully corrected the excessive hypoxia of VEGF-deficient chondrocytes, and completely prevented chondrocyte death. Yet, similarly crossed double-mutant embryos lacking HIF-1a and overexpressing VEGF164 in the growth plate cartilage still displayed a central cell death phenotype, albeit slightly delayed and less severe compared with mice exclusively lacking HIF-1a. Transgenic VEGF164 induced massive angiogenesis in the perichondrium, yet this only partially relieved the aberrant hypoxia present in HIF-1adeficient cartilage and thereby likely inflicted only a partial rescue effect. In fact, excessive hypoxia and failure to upregulate phosphoglycerate-kinase 1 (PGK1), a key enzyme of anaerobic glycolytic metabolism, were among the earliest manifestations of HIF-1a deficiency in cartilaginous bone templates, and reduced PGK1 expression was irrespective of transgenic VEGF164. These findings suggest that HIF-1a activates VEGF-independent cell-autonomous mechanisms to sustain oxygen levels in the challenged avascular cartilage by reducing oxygen consumption. Hence, regulation of the metabolic pathways by HIF-1a and VEGF-dependent regulation of angiogenesis coordinately act to maintain physiological cartilage oxygenation. We conclude that VEGF and HIF-1a are critical preservers of chondrocyte survival by ensuring an adequate balance between availability and handling of oxygen in developing growth cartilage. (c) 2012 American Society for Bone and Mineral Research C1 [Maes, Christa; Van Looveren, Riet; Carmeliet, Geert] KULeuven, Lab Expt Med & Endocrinol, Louvain, Belgium. [Araldi, Elisa; Khatri, Richa; Schipani, Ernestina] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. [Haigh, Katharina; Haigh, Jody J.] VIB, Dept Mol Biomed Res, Vasc Cell Biol Unit, Ghent, Belgium. [Haigh, Katharina; Haigh, Jody J.] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium. [Giaccia, Amato J.] Stanford Univ, Dept Radiat Oncol, Sch Med, Stanford, CA 94305 USA. RP Schipani, E (reprint author), Indiana Univ, Dept Med, Indianapolis, IN 46202 USA. EM geert.carmeliet@med.kuleuven.be; eschipan@iupui.edu FU National Institutes of Health [RO1 AR048191-06]; Fund for Scientific Research (FWO)-Flanders [G.0569.07, G.0500.08, G.0982.11] FX We thank Dr Henry M Kronenberg for helpful discussions, and Kim Atkin (Histology Core, Endocrine Unit, MGH), Karen Moermans, Ingrid Stockmans, and Sophie Torrekens (Legendo, KULeuven) for excellent technical help. We thank Napoleone Ferrara and Andras Nagy for the VEGF floxed and Rosa26-VEGF164 Tg mice used in this study. This work was supported by National Institutes of Health RO1 AR048191-06 (to ES) and Fund for Scientific Research (FWO)-Flanders G.0569.07 (to GC and JH) and G.0500.08 and G.0982.11 (to GC). NR 51 TC 28 Z9 28 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2012 VL 27 IS 3 BP 596 EP 609 DI 10.1002/jbmr.1487 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 897UG UT WOS:000300682500010 PM 22162090 ER PT J AU Schwartz, AV Johnson, KC Kahn, SE Shepherd, JA Nevitt, MC Peters, AL Walkup, MP Hodges, A Williams, CC Bray, GA AF Schwartz, Ann V. Johnson, Karen C. Kahn, Steven E. Shepherd, John A. Nevitt, Michael C. Peters, Anne L. Walkup, Michael P. Hodges, Amelia Williams, Carrie C. Bray, George A. CA Look AHEAD Res Grp TI Effect of 1 year of an intentional weight loss intervention on bone mineral density in type 2 diabetes: Results from the look AHEAD randomized trial SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE BONE MINERAL DENSITY; WEIGHT LOSS; TYPE 2 DIABETES; OBESITY; GLYCEMIC CONTROL; PHYSICAL FITNESS ID OVERWEIGHT POSTMENOPAUSAL WOMEN; LIFE-STYLE INTERVENTION; X-RAY ABSORPTIOMETRY; FRACTURE RISK; CARDIOVASCULAR-DISEASE; HIP FRACTURE; OLDER WOMEN; BODY-WEIGHT; MASS; ADULTS AB Intentional weight loss is an important component of treatment for overweight patients with type 2 diabetes, but the effects on bone density are not known. We used data from the Look AHEAD trial to determine the impact of an intensive lifestyle weight loss intervention (ILI) compared with diabetes support and education (DSE) on changes in bone mineral density (BMD) over 12 months. Overweight and obese adults with type 2 diabetes were randomly assigned to ILI or DSE. In a substudy of BMD conducted at 5 of 16 clinical centers, hip, spine, and whole body dual X-ray absorptiometry scans were obtained at baseline and 1-year later on 642 of 739 ILI and 632 of 740 DSE participants. At baseline, mean age was 58.4 years, and average body mass index was 35.2?kg/m2. Total hip BMD T-score was <-2.5 in 1% and <-1.0 in 8%. At 1 year, weight loss was greater in ILI than DSE (-8.6% versus -0.7%), and glycemic control and fitness were also improved. Bone loss over 1 year was greater in ILI at the total hip (-1.4% versus -0.4%; p? 16 units (on average) carried more information than multiband, multichannel LFPs. Furthermore, reach and grasp information added by various LFP frequency bands was not independent from that in SA ensembles but rather typically less than and primarily contained within the latter. Notably, MI and PMv did not show a particular bias toward reach or grasp for this task or for a broad range of signal types. For BCIs, our results indicate that neuronal ensemble spiking is the preferred signal for decoding, while LFPs and combined signals from PMv and MI can add robustness to BCI control. C1 [Bansal, Arjun K.; Truccolo, Wilson; Vargas-Irwin, Carlos E.; Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Truccolo, Wilson; Donoghue, John P.] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA. [Truccolo, Wilson] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Truccolo, Wilson; Donoghue, John P.] Dept Vet Affairs Med Ctr, Rehabil Res & Dev Serv, Providence, RI USA. RP Bansal, AK (reprint author), 3 Blackfan Circle,CLS 13th Floor 13077, Boston, MA 02115 USA. EM arjun.bansal@childrens.harvard.edu FU National Institutes of Health [National Institute of Neurological Disorders and Stroke (NINDS)] [F32-NS-061483, NS-25074, RO1-EB-007401-01]; National Center for Research Resources (NCRR) [C06-16549-01A1]; National Science Foundation [IIS-0534858]; Office of Naval Research [N00014-07-1-0803, N00014-16-1-0692]; NINDS [5K01-NS-057389]; DARPA [N66001-10-C-2010]; Katie Samson Foundation; Dana Foundation; Office of Research and Development, Rehabilitation R & D Service, Department of Veterans Affairs FX This research project was supported by the National Institutes of Health [National Institute of Neurological Disorders and Stroke (NINDS) F32-NS-061483, NS-25074, RO1-EB-007401-01] the National Center for Research Resources (NCRR C06-16549-01A1), the National Science Foundation (IIS-0534858), the Office of Naval Research (N00014-07-1-0803, award N00014-16-1-0692), NINDS Career Award 5K01-NS-057389 (W. Truccolo), DARPA (N66001-10-C-2010), the Katie Samson Foundation, Dana Foundation, Brown Brain Science Fellowship (A. K. Bansal), and the Office of Research and Development, Rehabilitation R & D Service, Department of Veterans Affairs. NR 56 TC 62 Z9 63 U1 0 U2 16 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 2012 VL 107 IS 5 BP 1337 EP 1355 DI 10.1152/jn.00781.2011 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 916TQ UT WOS:000302126500008 PM 22157115 ER PT J AU Williams, EC McFarland, LV Nelson, KM AF Williams, Emily C. McFarland, Lynne V. Nelson, Karin M. TI Alcohol Consumption Among Urban, Suburban, and Rural Veterans Affairs Outpatients SO JOURNAL OF RURAL HEALTH LA English DT Article DE alcohol abuse; health services research; health disparities; rural; veterans ID PRIMARY-CARE PATIENTS; BEHAVIORAL-COUNSELING INTERVENTIONS; IDENTIFICATION TEST AUDIT; HEALTH-STATUS; PREVENTIVE-SERVICES; DRINKING PATTERNS; SCREENING-TEST; RISK DRINKING; USE DISORDERS; MISUSE AB Purpose: United States rural residents tend toward poorer health than urban residents. Although alcohol use is associated with multiple medical conditions and can be reduced via brief primary care-based interventions, it is unknown whether alcohol consumption differs by rurality among primary care patients. We sought to describe alcohol consumption among urban, suburban, and rural Veterans Affairs (VA) outpatients. Methods: Outpatients from 7 VA facilities responded to mailed surveys that included the validated Alcohol Use Disorders Identification Test Consumption (AUDIT-C) screening questionnaire. The ZIP code approximation of the US Department of Agriculture's rural-urban commuting area (RUCA) codes classified participants into urban, suburban, and rural areas. For each area, adjusted logistic regression models estimated the prevalence of past-year abstinence among all participants and unhealthy alcohol use (AUDIT-C = 3 for women and = 4 for men) among drinkers. Findings: Among 33,883 outpatients, 14,967 (44%) reported abstinence. Among 18,916 drinkers, 8,524 (45%) screened positive for unhealthy alcohol use. The adjusted prevalence of abstinence was lowest in urban residents (43%, 95% CI 42%-43%) with significantly higher rates in both suburban and rural residents [ 45% (44%-46%) and 46% (45%-47%), respectively]. No significant differences were observed in the adjusted prevalence of unhealthy alcohol use among drinkers. Conclusions: Abstinence is slightly more common among rural and suburban than urban VA outpatients, but unhealthy alcohol use does not vary by rurality. As the VA and other health systems implement evidence-based care for unhealthy alcohol use, more research is needed to identify whether preventive strategies targeted to high-risk areas are needed. C1 [Williams, Emily C.; McFarland, Lynne V.; Nelson, Karin M.] Vet Affairs VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev HSR&D, Seattle, WA USA. [Nelson, Karin M.] Vet Affairs VA Puget Sound Hlth Care Syst, Gen Med Serv, Seattle, WA USA. [Williams, Emily C.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA USA. RP Williams, EC (reprint author), VA Puget Sound Hlth Care Syst, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM emily.williams3@va.gov FU US Department of Veterans Affairs, Office of Research and Development, VA Health Services [IIR 04-436-3]; Seattle Epidemiologic Research and Information Center; VA HSRD [SDR96-002, IIR99-376] FX This material is based upon work supported by the US Department of Veterans Affairs, Office of Research and Development, VA Health Services Research and Development Program (IIR 04-436-3), and the Seattle Epidemiologic Research and Information Center. The parent study, the VA Ambulatory Care Quality Improvement Project (ACQUIP), was funded by VA HSR&D Grants #SDR96-002 and IIR99-376. Views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the University of Washington. For further information, contact: Emily C. Williams, PhD, MPH; VA Puget Sound Health Care System; 1100 Olive Way, Suite 1400; Seattle, WA 98101; e-mail emily.williams3@va.gov. NR 49 TC 5 Z9 5 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0890-765X J9 J RURAL HEALTH JI J. Rural Health PD SPR PY 2012 VL 28 IS 2 BP 202 EP 210 DI 10.1111/j.1748-0361.2011.00389.x PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 916BI UT WOS:000302071200011 PM 22458321 ER PT J AU Kuye, IO Jain, NB Warner, L Herndon, JH Warner, JJP AF Kuye, Ifedayo O. Jain, Nitin B. Warner, Lauren Herndon, James H. Warner, Jon J. P. TI Economic evaluations in shoulder pathologies: a systematic review of the literature SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Review DE Shoulder surgery; shoulder pathology; cost-effectiveness; economic evaluation; cost-utility; cost-minimization; health economics ID ROTATOR CUFF REPAIR; COST-EFFECTIVENESS ANALYSIS; OPEN BANKART REPAIR; HEALTH-CARE; ARTHROSCOPIC ACROMIOPLASTY; IMPINGEMENT SYNDROME; ADHESIVE CAPSULITIS; RANDOMIZED-TRIAL; BENEFIT ANALYSES; THERAPY PROGRAM AB Background: Economic evaluations provide decision makers with a tool for reducing health care costs because they assess both the costs and consequences of health care interventions. This study reviewed the quality of published economic evaluations for shoulder pathologies. Materials and method: A MEDLINE search was conducted to identify articles published from 1980 to 2010 that contained "cost" or "economic" combined with terms for several shoulder disorders and treatments. We selected studies that fit the definition of 1 of the 4 routinely performed economic evaluations: cost-minimization, cost-effectiveness, cost-utility, and cost-benefit analyses. Study quality was determined by measuring adherence to 6 established health economic principles, as described in the literature. Results: The search retrieved 942 studies. Of these, 32 were determined to be economic evaluations, and 53% of the economic evaluations were published from 2005 to 2010. Only 8 of the 32 studies (25%) adhered to all 6 health economic principles. Publication in a nonsurgical journal (P < .05) or in more recent years (P < .01) was significantly associated with higher quality. Conclusion: Future health care resource allocation will likely be based on the economic feasibility of treatments. Although the number and quality of economic evaluations of shoulder disorders have risen in recent years, the current state of the literature is poor. Given that availability of such data may factor in private and public reimbursement decisions, there is a clear demand for more rigorous economic evaluations. Level of evidence: Level IV, Systematic Review of Economic and Decision Analyses. (C) 2012 Journal of Shoulder and Elbow Surgery Board of Trustees. C1 [Warner, Jon J. P.] Massachusetts Gen Hosp, Harvard Shoulder Serv, Dept Orthoped, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. [Jain, Nitin B.] Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA. [Jain, Nitin B.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Jain, Nitin B.] Harvard Univ, Sch Med, Boston, MA USA. [Warner, Lauren] Colgate Univ, Hamilton, NY 13346 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Harvard Shoulder Serv, Dept Orthoped, Yawkey Ctr Outpatient Care, 55 Fruit St,Ste 3200,3G,Rm 3-046, Boston, MA 02114 USA. EM jwarner@partners.org FU National institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [1K23AR059199]; Foundation for PMR; Biomedical Research Institute at Brigham and Women's Hospital FX Dr Jain is supported by funding from the National institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; project no. 1K23AR059199), the Foundation for PM&R, and the Biomedical Research Institute at Brigham and Women's Hospital. The remaining authors, their immediate families, and any research foundations with which they are affiliated have not received any financial payments or other benefits from any commercial entity related to the subject of this article. NR 54 TC 6 Z9 6 U1 1 U2 6 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 MAR PY 2012 VL 21 IS 3 BP 367 EP 375 DI 10.1016/j.jse.2011.05.019 PG 9 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 919AD UT WOS:000302292100018 PM 21865060 ER PT J AU Ring, D AF Ring, David TI Regarding the "Editor's Note" SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAR PY 2012 VL 21 IS 3 BP E21 EP E22 DI 10.1016/j.jse.2011.10.025 PG 3 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 919AD UT WOS:000302292100006 PM 22420044 ER PT J AU Taylor, JS DeMers, SM Vig, EK Borson, S AF Taylor, Janelle S. DeMers, Shaune M. Vig, Elizabeth K. Borson, Soo TI The Disappearing Subject: Exclusion of People with Cognitive Impairment and Dementia from Geriatrics Research SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE exclusion criteria; research methodologies ID DECISION-MAKING CAPACITY; RESEARCH CONSENT CAPACITY; NURSING-HOME RESIDENTS; QUALITY-OF-LIFE; OLDER-ADULTS; AGING RESEARCH; INCONTINENCE; INDIVIDUALS; MEDICATION; STRATEGIES AB OBJECTIVES: To evaluate exclusion of persons with cognitive impairment from research in geriatrics by determining its frequency, method, and rationale and treatment in the resulting publications. DESIGN: All original research articles published in 2008 and 2009 in the Journal of the American Geriatrics Society (n = 434) were reviewed using a structured data collection tool. SETTING: The Journal of the American Geriatrics Society. PARTICIPANTS: There were no participants in this study. MEASUREMENTS: Data captured included recruitment method, explicit criterion for exclusion of persons with cognitive impairment, justification of exclusion criterion, reason given for exclusion, percentage of individuals excluded, and mention of exclusion as a possible limitation. RESULTS: Of 434 articles examined, 16% used recruitment methods likely to reduce participation by persons with cognitive impairment. At least 29% of studies (n = 127) employed explicit exclusion criteria. Half used the Folstein Mini-Mental State Examination (MMSE), with variable cut points (10, 12, 17, 18, 23, 26), and 19% excluded individuals for "having dementia" without specifying how this was determined. Few (6%) provided any justification for exclusion criteria used, only 43% gave any reason for exclusion, and only 14% discussed exclusion as a possible limitation. CONCLUSION: Persons with cognitive impairment are frequently excluded from research, often without rationale or mention of exclusion as a limitation or any discussion of its potential effect on the evidence base in geriatrics. When necessary, exclusion should be done thoughtfully and with awareness that this may reduce the clinical utility of study findings. J Am Geriatr Soc 60:413-419, 2012. C1 [Taylor, Janelle S.] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. [DeMers, Shaune M.; Borson, Soo] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Vig, Elizabeth K.] Univ Washington, Dept Geriatr, Seattle, WA 98195 USA. [Vig, Elizabeth K.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Taylor, JS (reprint author), Univ Washington, Dept Anthropol, Box 353100, Seattle, WA 98195 USA. EM jstaylor@uw.edu NR 37 TC 21 Z9 21 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2012 VL 60 IS 3 BP 413 EP 419 DI 10.1111/j.1532-5415.2011.03847.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 906KM UT WOS:000301344000002 PM 22288835 ER PT J AU Stineman, MG Xie, DW Pan, Q Kurichi, JE Zhang, Z Saliba, D Henry-Sanchez, JT Streim, J AF Stineman, Margaret G. Xie, Dawei Pan, Qiang Kurichi, Jibby E. Zhang, Zi Saliba, Debra Henry-Sanchez, John T. Streim, Joel TI All-Cause 1-, 5-, and 10-Year Mortality in Elderly People According to Activities of Daily Living Stage SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE activities of daily living; staging; mortality; risk factors ID CASE-MIX; PHYSICAL INDEPENDENCE; FUNCTIONAL STATUS; OLDER-ADULTS; HEALTH; VALIDATION; DISABILITY; INDEX; LIFE; HOSPITALIZATION AB OBJECTIVES: To examine the independent association between five stages of activities of daily living (ADLs) and mortality after accounting for known diagnostic and sociodemographic risk factors. DESIGN: For five stages of ADLs (0 to IV), determined according to the severity and pattern of ADL limitations, unadjusted life expectancies and adjusted associations with mortality were estimated using a Cox proportional hazards regression model. SETTING: Community, PARTICIPANTS: Nine thousand four hundred forty-seven participants aged 70 and older from the second Longitudinal Study of Aging. MEASUREMENTS: One-, 5-, and 10-year survival and time to death. RESULTS: Median life expectancy was 10.6 years for participants with no ADL limitations and 6.5, 5.1, 3.8, and 1.6 years for those at ADL stages I, II, III, and IV, respectively. The sociodemographic-and diagnosticadjusted hazard of death at 1 year was five times as great at stage IV as at stage 0 (hazard ratio = 5.6, 95% confidence interval = 3.8-8.3). The associations between ADL stage and mortality declined over time but remained statistically significant at 5 and 10 years. CONCLUSION: ADL stage continued to explain mortality risk after adjusting for known risk factors including advanced age, stroke, and cancer. ADL stages might aid clinical care planning and policy as a powerful prognostic indicator particularly of short-term mortality, improving on current ADL measures by profiling activity limitations of relevance to determining community support needs. J Am Geriatr Soc 60:485-492, 2012. C1 [Stineman, Margaret G.; Xie, Dawei; Pan, Qiang; Kurichi, Jibby E.; Zhang, Zi] Univ Calif Los Angeles, Dept Biostat & Epidemiol, JH Borun Ctr Gerontol Res, Ctr Clin Epidemiol & Biostat, Los Angeles, CA USA. [Stineman, Margaret G.] Univ Calif Los Angeles, Dept Phys Med & Rehabil, JH Borun Ctr Gerontol Res, Perelman Sch Med, Los Angeles, CA USA. [Saliba, Debra] Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Geriatr Res Educ, JH Borun Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, Debra] RAND Corp, Santa Monica, CA USA. [Henry-Sanchez, John T.] Hosp La Concepc, San German, PR USA. [Streim, Joel] Univ Penn, Geriatr Psychiat Sect, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Streim, Joel] Philadelphia Vet Affairs Med Ctr, Vet Integrated Serv Network Mental Illness Res Ed, Philadelphia, PA USA. RP Stineman, MG (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Geriatr Psychiat Sect, Dept Psychiat,Perelman Sch Med, 904 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM mstinema@exchange.upenn.edu FU National Institutes of Health [AG032420 -01A1]; National Institute of Child Health and Human Development, National Center for Medical Rehabilitation Research [T32-HD-007425] FX The research for this manuscript was supported by the National Institutes of Health (AG032420 -01A1) and a Post-Doctoral Fellowship for Dr. Henry-Sanchez (T32-HD-007425) awarded to the University of Pennsylvania from the National Institute of Child Health and Human Development, National Center for Medical Rehabilitation Research. NR 42 TC 33 Z9 33 U1 3 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2012 VL 60 IS 3 BP 485 EP 492 DI 10.1111/j.1532-5415.2011.03867.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 906KM UT WOS:000301344000012 PM 22352414 ER PT J AU King, J Yourman, L Ahalt, C Eng, C Knight, SJ Perez-Stable, EJ Smith, AK AF King, Jennifer Yourman, Lindsey Ahalt, Cyrus Eng, Catherine Knight, Sara J. Perez-Stable, Eliseo J. Smith, Alexander K. TI Quality of Life in Late-Life Disability: "I Don't Feel Bitter Because I Am in a Wheelchair" SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE ethnicity; quality of life; disability ID OLDER AGES; LAST YEAR; HEALTH; MODEL; TRAJECTORIES; CHALLENGE; DECLINE; FRAIL; CARE AB OBJECTIVES: To determine perceived quality of life in a diverse population of elderly adults with late-life disability. DESIGN: Qualitative cross-sectional study. SETTING: Community-dwelling participants were recruited from San Francisco's On Lok Lifeways program, the first Program of All-inclusive Care for the Elderly. On Lok enrollees meet Medicaid criteria for nursing home placement. PARTICIPANTS: Sixty-two elderly adults with a mean age of 78 and a mean 2.4 activity of daily living dependencies and 6.6 instrumental activity of daily living dependencies were interviewed. Respondents were 63% female, 24% white, 19% black, 18% Latino, 32% Chinese American, and 6% other race. MEASUREMENTS: Elderly adults who scored higher than 17 points on the Mini-Mental State Examination were interviewed. Interviews were conducted in English, Spanish, and Cantonese. Respondents were asked to rate their overall quality of life on a 5-point scale. Open-ended questions explored positive and negative aspects of participants' daily experiences. Interviews were analyzed using modified grounded theory and digital coding software. RESULTS: Eighty-seven percent of respondents rated their quality of life in the middle range of the quality-of-life spectrum (fair to very good). Themes were similar across ethnic groups. Most themes could be grouped into four domains that dependent elderly adults considered important to their quality of life: physical (e.g., pain), psychological (e.g., depression), spiritual or religious (e.g., religious coping), and social (e.g., life-space). Dignity and a sense of control were identified as themes that are the most closely tied to overall quality of life. CONCLUSION: Factors that influence quality of life in late-life disability were similar across ethnic groups. As the number of elderly adults from diverse backgrounds with late life disability increases in the United States, interventions should be targeted to maximize daily sense of control and dignity. J Am Geriatr Soc 60:569-576, 2012. C1 [Yourman, Lindsey; Ahalt, Cyrus; Eng, Catherine; Smith, Alexander K.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94121 USA. [Perez-Stable, Eliseo J.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94121 USA. [Knight, Sara J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94121 USA. [Perez-Stable, Eliseo J.] Univ Calif San Francisco, Med Effectiveness Res Ctr Div Populat, San Francisco, CA 94121 USA. [King, Jennifer] Univ Calif San Francisco, Sch Med, San Francisco, CA 94121 USA. [Ahalt, Cyrus; Knight, Sara J.; Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Eng, Catherine; Knight, Sara J.] Lok Lifeways, San Francisco, CA USA. RP Smith, AK (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, 4150 Clement St,181G, San Francisco, CA 94121 USA. EM aksmith@ucsf.edu FU Resource Centers for Minority Aging Research [P30-AG15272]; National Institute on Aging, National Institutes of Health; National Center for Research Resources UCSF-CTSI [UL1 RR024131]; Atlantic Philanthropies; Society of General Internal Medicine; John A. Hartford Foundation; Association of Specialty Professors FX Dr. Smith was supported by Grant P30-AG15272 of the Resource Centers for Minority Aging Research program funded by the National Institute on Aging, National Institutes of Health. Additional support provided by the National Center for Research Resources UCSF-CTSI (UL1 RR024131), Atlantic Philanthropies, the Society of General Internal Medicine, the John A. Hartford Foundation, and the Association of Specialty Professors. An early version of this paper was presented in abstract form at the 2011 Annual Meetings of the American Geriatrics Society, National Harbor, Maryland, and the Society of General Internal Medicine, Phoenix, Arizona. NR 26 TC 16 Z9 16 U1 3 U2 24 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2012 VL 60 IS 3 BP 569 EP 576 DI 10.1111/j.1532-5415.2011.03844.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 906KM UT WOS:000301344000024 PM 22288767 ER PT J AU Noble, VE AF Noble, Vicki E. TI Think Ultrasound When Evaluating for Pneumothorax SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Editorial Material ID TRAUMATIC PNEUMOTHORAX; BEDSIDE ULTRASOUND; CHEST RADIOGRAPHY C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Noble, VE (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 0 Emerson,3B,55 Fruit St, Boston, MA 02114 USA. EM vnoble@partners.org NR 7 TC 5 Z9 5 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 2012 VL 31 IS 3 BP 501 EP 504 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 905ZZ UT WOS:000301316000019 PM 22368142 ER PT J AU Kam, WWY Wu, X Chan, ST AF Kam, Winnie Wai-Ying Wu, Xing Chan, Suk-Tak TI The feasibility of 2-back task with alphabets and functional transcranial Doppler sonography in assessing hemispheric lateralization of working memory in Chinese SO NEUROLOGY ASIA LA English DT Article ID FLOW-VELOCITY CHANGES; CEREBRAL-BLOOD-FLOW; EVENT-RELATED FMRI; LANGUAGE LATERALIZATION; PREFRONTAL CORTEX; COGNITIVE TASKS; WADA TEST; BRAIN ACTIVATION; MRI; CHARACTERS AB Background: Hemispheric asymmetry studies of working memory are mainly carried out in western countries. Data on Chinese is limited in this area of research. On the other hand, working memory assessment can be limited by the temporal resolution of the imaging modality as well as the design of the cognitive paradigm. These methodological limitations influence result interpretation hence hinder cross study comparison. Hemispheric study of memory using a pure working memory paradigm on native Chinese speakers, using a hemodynamic technique with high temporal resolution is thus mandatory. Objective: We aimed to investigate the feasibility of the functional transcranial Doppler sonography (fTCD) and 2-back task with alphabets in assessing the hemispheric lateralization of memory in healthy right-handed Chinese. Methods: Thirteen healthy right-handed Chinese subjects (7 males and 6 females, 19-22 years old) were included. Bilateral monitoring of the cerebral blood flow velocity (CFBV) changes in their left and right middle cerebral arteries (MCAs) was performed using fTCD during their performance of a 2-back working memory task with alphabets. Differences of CBFV change between left and right MCAs were analyzed, and the laterality index (LI) was determined. Results: Left lateralization was found in all subjects, with females performed better than males (p < 0.05). No difference in age, response time and LI between the male and female subjects could be observed (p > 0.05). A weak correlation was found between performance accuracy/response time and LI (r(2) = 0.12). Conclusion: To the best of our knowledge, this is the first report on the use of fTCD in memory function assessment in Chinese. The consistency of our results with previous studies demonstrates the feasibility as well as the potential application of the 2-back task with alphabets and fTCD, as a bedside assessment system of memory function in native Chinese speaking population. C1 [Kam, Winnie Wai-Ying] Australian Nucl Sci & Technol Org, Lucas Heights, NSW 2234, Australia. [Wu, Xing] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China. [Chan, Suk-Tak] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Kam, WWY (reprint author), Australian Nucl Sci & Technol Org, Lucas Heights, NSW 2234, Australia. EM wik@ansto.gov.au RI Kam, Winnie/B-7407-2013; Chan, Suk-tak/G-5846-2015 OI Kam, Winnie/0000-0002-5508-2432; NR 50 TC 0 Z9 0 U1 0 U2 6 PU ASEAN NEUROLOGICAL ASSOC PI KUALA LUMPUR PA UNIV MALAYA MEDICAL CENTRE, NEUROLOGY LABORATORY, KUALA LUMPUR, 59100, MALAYSIA SN 1823-6138 J9 NEUROL ASIA JI Neurol. Asia PD MAR PY 2012 VL 17 IS 1 BP 39 EP 48 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 917GI UT WOS:000302160400006 ER PT J AU Manchikanti, L Singh, V Hirsch, JA AF Manchikanti, Laxmaiah Singh, Vijay Hirsch, Joshua A. TI Saga of Payment Systems of Ambulatory Surgery Centers for Interventional Techniques: An Update SO PAIN PHYSICIAN LA English DT Review DE Outpatient prospective payment system; ambulatory surgery center payment system; Government Accountability Office; Medicare Modernization and Improvement Act; interventional techniques ID EPIDURAL STEROID INJECTIONS; LOW-BACK-PAIN; CHRONIC SPINAL PAIN; ACTIVE CONTROLLED-TRIAL; LUMBAR DISC HERNIATION; AFFORDABLE CARE ACT; DOUBLE-BLIND TRIAL; EQUIVALENCE CONTROLLED-TRIAL; CLINICAL-PRACTICE GUIDELINES; DRUG-MONITORING PROGRAMS AB The health care system in the United States has been criticized for skyrocketing expenditures and quality deficits. Simultaneously, health care providers and systems are under pressure to provide better and more proficient care. The landscape of the US health care system is shaped by federal and private payers which continue to develop initiatives designed to curtail costs. These include value-based reimbursement programs; cost-shifting expenses to the consumer and reducing reimbursement of providers and facilities. Moreover, there is an underlying thought to steer provision of health care to theoretically more efficient settings. Many of these initiatives are based on affordable health care reform. The major aspects of curtailing health care costs include hospital and other facility payments as well as physician payments and reductions in the approved services. Consequently, ambulatory surgery centers (ASCs) are not immune to these changes. Until 1970, all surgery was performed in hospitals The development of ASCs and site of service differential payments for in-office procedures have changed the dynamics of surgical trends with outpatient surgeries outpacing inpatient surgeries by as early as 1989. By 2008, approximately 65% of procedures were performed in all outpatient settings including hospital outpatient departments. ASCs claim that improved efficiency in health care delivery allows patients to spend less time in the health care setting with quicker turn over, improving the productivity of the health care team. However, since the majority of the ASCs are owned, in part, by the physicians who staff them, the financial incentives related to ownership have been alleged to potentially alter provider behavior. The number of Medicare certified ASCs and total Medicare payments from 1999 to 2010 increased significantly, but more recent year-to-year changes are far less substantial when compared to previous years. Net percent revenue growth from 2008 to 2009 was 3.2% and from 2009 to 2010 was 6.2% with an overall increase from 1999 of 183% over a period of 11 years. Similarly, the number of Medicare certified ASCs increased from 2,786 in 1999 to 5,316 in 2010, 1.1% increased from 2009 to 2010, however, a 91% increase from 1999 over a period of 11 years. Interventional pain management is one of the fastest growing specialties with a footprint in multiple disciplines. Interventional pain management in ASC settings has come a long way since June 1998 proposed Health Care Financing Administration's ASC rule which seriously compromised interventional pain management in the ASC setting. There are many payment challenges facing interventional pain management (IPM) in 2012. Significant changes continue to occur in the payment systems with policies of paying a certain percent of hospital outpatient department payments to ASCs which declined from 63% in 2008 to 56% in 2011, with substantial reductions for add-on codes. The Centers for Medicare and Medicaid Services (CMS) evaluation of IPM codes also consists of multiple misvalued codes. In conclusion, overall the future of ASCs may appear optimistic, but in the near perspective, specifically in 2012 to 2014, there will be challenging times specifically for interventional pain management centers with the regulatory environment and rapid changes taking place with or without implementation of Affordable Care Act. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Singh, Vijay] Pain Diagnost Associates, Niagara, WI USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 148 TC 16 Z9 16 U1 5 U2 8 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAR-APR PY 2012 VL 15 IS 2 BP 109 EP 130 PG 22 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 913ZY UT WOS:000301917800011 PM 22430649 ER PT J AU Hirsch, JA Falco, F Manchikanti, L AF Hirsch, Joshua A. Falco, Frank Manchikanti, Laxmaiah TI Necessity and Implications of ICD-10: Facts and Fallacies SO PAIN PHYSICIAN LA English DT Letter C1 [Hirsch, Joshua A.] Mass Gen Hosp, Boston, MA 02114 USA. [Falco, Frank] Mid Atlantic Spine, Newark, DE 19713 USA. [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. RP Hirsch, JA (reprint author), Mass Gen Hosp, GRB 241, Boston, MA 02114 USA. EM HIrsch@snisonline.org; cssm01@aol.com; drlm@thepainmd.com NR 1 TC 0 Z9 0 U1 0 U2 1 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD MAR-APR PY 2012 VL 15 IS 2 BP E153 EP E153 PG 1 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 913ZY UT WOS:000301917800005 PM 22430662 ER PT J AU Martel, JM Toner, M AF Martel, Joseph M. Toner, Mehmet TI Inertial focusing dynamics in spiral microchannels SO PHYSICS OF FLUIDS LA English DT Article ID CELL-SEPARATION; POISEUILLE FLOW; MICROFLUIDIC SYSTEMS; REYNOLDS-NUMBER; PARTICLE; FILTRATION; MIGRATION; DEVICE AB This report details a comprehensive study of inertial focusing dynamics and particle behavior in low aspect ratio (h/w similar to 1/1 to 1/8) spiral microchannels. A continuum of particle streak behavior is shown with longitudinal, cross-sectional, and velocity resolution, yielding a large analyzed parameter space. The dataset is then summarized and compared to prior results from both straight microchannels and other low aspect ratio spiral microchannel designs. Breakdown of focusing into a primary and secondary fluorescent streak is observed in the lowest aspect ratio channels at high average downstream velocities. Streak movement away from the theoretically predicted near inner wall equilibrium position towards the center of the channel at high average downstream velocities is also detailed as a precursor to breakdown. State diagrams detail the overall performance of each device including values of the required channel lengths and the range of velocities over which quality focusing can be achieved. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.3681228] C1 [Martel, Joseph M.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Martel, Joseph M.; Toner, Mehmet] Massachusetts Gen Hosp, BioMEMS Resource Ctr, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Martel, Joseph M.; Toner, Mehmet] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Martel, JM (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM joseph.m.martel@gmail.com FU National Institute of Biomedical Imaging and Bioengineering (BioMEMS Resource Center) [P41 EB002503] FX Joseph M. Martel is a National Science Foundation Graduate Research Fellow. This work was supported in part by the National Institute of Biomedical Imaging and Bioengineering (BioMEMS Resource Center, P41 EB002503). The authors thank Octavio Hurtado for microfabrication training, Bryan Hassel for his help generating straightened images, as well as Anh Hoang, Ian Wong, Daniel Irimia, and Dino Di Carlo for their assistance in editing the paper. NR 33 TC 44 Z9 44 U1 4 U2 46 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 1070-6631 J9 PHYS FLUIDS JI Phys. Fluids PD MAR PY 2012 VL 24 IS 3 AR 032001 DI 10.1063/1.3681228 PG 13 WC Mechanics; Physics, Fluids & Plasmas SC Mechanics; Physics GA 918BT UT WOS:000302224600004 PM 22454556 ER PT J AU Shimazaki, H Amari, S Brown, EN Grun, S AF Shimazaki, Hideaki Amari, Shun-ichi Brown, Emery N. Gruen, Sonja TI State-Space Analysis of Time-Varying Higher-Order Spike Correlation for Multiple Neural Spike Train Data SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID CELL ASSEMBLIES; UNITARY EVENTS; NEURONAL INTERACTIONS; SOMATOSENSORY CORTEX; INFORMATION GEOMETRY; MAXIMUM-LIKELIHOOD; BOLTZMANN MACHINES; PREFRONTAL CORTEX; CORTICAL NETWORKS; DYNAMIC-ANALYSIS AB Precise spike coordination between the spiking activities of multiple neurons is suggested as an indication of coordinated network activity in active cell assemblies. Spike correlation analysis aims to identify such cooperative network activity by detecting excess spike synchrony in simultaneously recorded multiple neural spike sequences. Cooperative activity is expected to organize dynamically during behavior and cognition; therefore currently available analysis techniques must be extended to enable the estimation of multiple time-varying spike interactions between neurons simultaneously. In particular, new methods must take advantage of the simultaneous observations of multiple neurons by addressing their higher-order dependencies, which cannot be revealed by pairwise analyses alone. In this paper, we develop a method for estimating time-varying spike interactions by means of a state-space analysis. Discretized parallel spike sequences are modeled as multi-variate binary processes using a log-linear model that provides a well-defined measure of higher-order spike correlation in an information geometry framework. We construct a recursive Bayesian filter/smoother for the extraction of spike interaction parameters. This method can simultaneously estimate the dynamic pairwise spike interactions of multiple single neurons, thereby extending the Ising/spin-glass model analysis of multiple neural spike train data to a nonstationary analysis. Furthermore, the method can estimate dynamic higher-order spike interactions. To validate the inclusion of the higher-order terms in the model, we construct an approximation method to assess the goodness-of-fit to spike data. In addition, we formulate a test method for the presence of higher-order spike correlation even in nonstationary spike data, e. g., data from awake behaving animals. The utility of the proposed methods is tested using simulated spike data with known underlying correlation dynamics. Finally, we apply the methods to neural spike data simultaneously recorded from the motor cortex of an awake monkey and demonstrate that the higher-order spike correlation organizes dynamically in relation to a behavioral demand. C1 [Shimazaki, Hideaki; Amari, Shun-ichi; Gruen, Sonja] RIKEN Brain Sci Inst, Wako, Saitama, Japan. [Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Brown, Emery N.] Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gruen, Sonja] Forschungszentrum Julich, Inst Neurosci & Med INM 6, D-52425 Julich, Germany. [Gruen, Sonja] Rhein Westfal TH Aachen, Aachen, Germany. RP Shimazaki, H (reprint author), RIKEN Brain Sci Inst, Wako, Saitama, Japan. EM shimazaki@brain.riken.jp RI Shimazaki, Hideaki/C-8606-2009; Grun, Sonja/I-6321-2013; Amari, Shun-ichi/A-5901-2016 OI Shimazaki, Hideaki/0000-0001-7794-3064; Grun, Sonja/0000-0003-2829-2220; FU JSPS; RIKEN; [R01 MH59733]; [DP1 OD003646]; [R01 MH071847] FX This work was supported in part by JSPS Research Fellowships for Young Scientists (HS), R01 MH59733 (ENB), DP1 OD003646 (ENB), R01 MH071847 (ENB), and RIKEN Strategic Programs for R&D (SG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 111 TC 33 Z9 33 U1 1 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAR PY 2012 VL 8 IS 3 AR e1002385 DI 10.1371/journal.pcbi.1002385 PG 27 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 918IY UT WOS:000302244000002 PM 22412358 ER PT J AU Henn, MR Boutwell, CL Charlebois, P Lennon, NJ Power, KA Macalalad, AR Berlin, AM Malboeuf, CM Ryan, EM Gnerre, S Zody, MC Erlich, RL Green, LM Berical, A Wang, YY Casali, M Streeck, H Bloom, AK Dudek, T Tully, D Newman, R Axten, KL Gladden, AD Battis, L Kemper, M Zeng, QD Shea, TP Gujja, S Zedlack, C Gasser, O Brander, C Hess, C Gunthard, HF Brumme, ZL Brumme, CJ Bazner, S Rychert, J Tinsley, JP Mayer, KH Rosenberg, E Pereyra, F Levin, JZ Young, SK Jessen, H Altfeld, M Birren, BW Walker, BD Allen, TM AF Henn, Matthew R. Boutwell, Christian L. Charlebois, Patrick Lennon, Niall J. Power, Karen A. Macalalad, Alexander R. Berlin, Aaron M. Malboeuf, Christine M. Ryan, Elizabeth M. Gnerre, Sante Zody, Michael C. Erlich, Rachel L. Green, Lisa M. Berical, Andrew Wang, Yaoyu Casali, Monica Streeck, Hendrik Bloom, Allyson K. Dudek, Tim Tully, Damien Newman, Ruchi Axten, Karen L. Gladden, Adrianne D. Battis, Laura Kemper, Michael Zeng, Qiandong Shea, Terrance P. Gujja, Sharvari Zedlack, Carmen Gasser, Olivier Brander, Christian Hess, Christoph Guenthard, Huldrych F. Brumme, Zabrina L. Brumme, Chanson J. Bazner, Suzane Rychert, Jenna Tinsley, Jake P. Mayer, Ken H. Rosenberg, Eric Pereyra, Florencia Levin, Joshua Z. Young, Sarah K. Jessen, Heiko Altfeld, Marcus Birren, Bruce W. Walker, Bruce D. Allen, Todd M. TI Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection SO PLOS PATHOGENS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE ESCAPE; CELL RESPONSES; REVERSE-TRANSCRIPTASE; DRUG-RESISTANCE; VACCINE DESIGN; IN-VIVO; GAG; MUTATIONS; TRANSMISSION AB Deep sequencing technologies have the potential to transform the study of highly variable viral pathogens by providing a rapid and cost-effective approach to sensitively characterize rapidly evolving viral quasispecies. Here, we report on a high-throughput whole HIV-1 genome deep sequencing platform that combines 454 pyrosequencing with novel assembly and variant detection algorithms. In one subject we combined these genetic data with detailed immunological analyses to comprehensively evaluate viral evolution and immune escape during the acute phase of HIV-1 infection. The majority of early, low frequency mutations represented viral adaptation to host CD8+ T cell responses, evidence of strong immune selection pressure occurring during the early decline from peak viremia. CD8+ T cell responses capable of recognizing these low frequency escape variants coincided with the selection and evolution of more effective secondary HLA-anchor escape mutations. Frequent, and in some cases rapid, reversion of transmitted mutations was also observed across the viral genome. When located within restricted CD8 epitopes these low frequency reverting mutations were sufficient to prime de novo responses to these epitopes, again illustrating the capacity of the immune response to recognize and respond to low frequency variants. More importantly, rapid viral escape from the most immunodominant CD8+ T cell responses coincided with plateauing of the initial viral load decline in this subject, suggestive of a potential link between maintenance of effective, dominant CD8 responses and the degree of early viremia reduction. We conclude that the early control of HIV-1 replication by immunodominant CD8+ T cell responses may be substantially influenced by rapid, low frequency viral adaptations not detected by conventional sequencing approaches, which warrants further investigation. These data support the critical need for vaccine-induced CD8+ T cell responses to target more highly constrained regions of the virus in order to ensure the maintenance of immunodominant CD8 responses and the sustained decline of early viremia. C1 [Henn, Matthew R.; Charlebois, Patrick; Lennon, Niall J.; Macalalad, Alexander R.; Berlin, Aaron M.; Malboeuf, Christine M.; Ryan, Elizabeth M.; Gnerre, Sante; Zody, Michael C.; Erlich, Rachel L.; Green, Lisa M.; Casali, Monica; Newman, Ruchi; Zeng, Qiandong; Shea, Terrance P.; Gujja, Sharvari; Levin, Joshua Z.; Young, Sarah K.; Birren, Bruce W.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Boutwell, Christian L.; Power, Karen A.; Berical, Andrew; Wang, Yaoyu; Streeck, Hendrik; Bloom, Allyson K.; Dudek, Tim; Tully, Damien; Axten, Karen L.; Gladden, Adrianne D.; Battis, Laura; Kemper, Michael; Brumme, Zabrina L.; Brumme, Chanson J.; Pereyra, Florencia; Altfeld, Marcus; Walker, Bruce D.; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Zedlack, Carmen; Jessen, Heiko] HIV Clin Praxis Jessen, Berlin, Germany. [Gasser, Olivier; Hess, Christoph] Univ Basel Hosp, Dept Biomed, Immunobiol Lab, CH-4031 Basel, Switzerland. [Brander, Christian] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain. [Brander, Christian] Hosp Badalona Germans Trias & Pujol, Irsicaixa AIDS Res Inst HIVACAT, Badalona, Spain. [Guenthard, Huldrych F.] Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, CH-8006 Zurich, Switzerland. [Bazner, Suzane; Rychert, Jenna; Rosenberg, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bazner, Suzane; Rychert, Jenna; Rosenberg, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Tinsley, Jake P.; Mayer, Ken H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Henn, MR (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA. EM tallen2@partners.org RI gunthard, huldrych/F-1724-2011; Gasser, Olivier/I-3663-2013; Infektiologie, USZ/A-6921-2011; SHCS, all/G-4072-2011; SHCS, int. coll. A/G-4083-2011; Allen, Todd/F-5473-2011; OI gunthard, huldrych/0000-0002-1142-6723; Brander, Christian/0000-0002-0548-5778; Brumme, Chanson/0000-0003-2722-5288 FU Bill and Melinda Gates Foundation; National Institute of Allergy and Infectious Disease; National Institutes of Health; Department of Health and Human Services [NIAID P01-AI074415, NIAID T32-AI07245, HHSN272200900018C, HHSN272200900006C]; Ragon Institute of MGH, MIT and Harvard; Swiss HIV Cohort Study (SHCS) [535]; Swiss National Science Foundation (SNF) [33CSC0-108787] FX This project was funded in part with Federal funds from the Bill and Melinda Gates Foundation (BDW, TMA), the National Institute of Allergy and Infectious Disease, the National Institutes of Health, and the Department of Health and Human Services under grants NIAID P01-AI074415 (TMA, MA), NIAID T32-AI07245 (CLB), and contracts no. HHSN272200900018C (BWB) and HHSN272200900006C (BWB), as well as by an Innovation Award from the Ragon Institute of MGH, MIT and Harvard (TMA and MRH) and by the Swiss HIV Cohort Study (SHCS) project No. 535 (OG, CH, and HFG). We also thank the International HIV Controllers Study and the SHCS, supported by the Swiss National Science Foundation (SNF # 33CSC0-108787) for collaboration. NR 65 TC 139 Z9 144 U1 1 U2 33 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD MAR PY 2012 VL 8 IS 3 AR e1002529 DI 10.1371/journal.ppat.1002529 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 918CC UT WOS:000302225600005 PM 22412369 ER PT J AU Pfeiffer, PN Valenstein, M AF Pfeiffer, Paul N. Valenstein, Marcia TI Assessing the Costs of Second-Generation Antipsychotics SO PSYCHIATRIC SERVICES LA English DT Editorial Material C1 [Pfeiffer, Paul N.] Univ Michigan, US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Pfeiffer, PN (reprint author), Univ Michigan, US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2012 VL 63 IS 3 BP 199 EP 199 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 917NV UT WOS:000302185600001 PM 22388524 ER PT J AU Kilbourne, AM Neumann, MS Waxmonsky, J Bauer, MS Kim, HM Pincus, HA Thomas, M AF Kilbourne, Amy M. Neumann, Mary Spink Waxmonsky, Jeanette Bauer, Mark S. Kim, Hyungin Myra Pincus, Harold Alan Thomas, Marshall TI Evidence-Based Implementation: The Role of Sustained Community-Based Practice and Research Partnerships SO PSYCHIATRIC SERVICES LA English DT Editorial Material ID HEALTH-SERVICES RESEARCH; SCIENCE AB This column describes a process for adapting an evidence-based practice in community clinics in which researchers and community providers participated and the resulting framework for implementation of the practice Replicating Effective Programs Facilitation. A two-day meeting for the Recovery-Oriented Collaborative Care study was conducted to elicit input from more than 50 stakeholders, including community providers, health care administrators, and implementation researchers. The process illustrates an effective researcher-community partnership in which stakeholders worked together not only to adapt the evidence-based practice to the needs of the clinical settings but also to develop the implementation strategy. (Psychiatric Services 63:205 207, 2012; doi: 10.1176/appi.ps.201200032) C1 [Kilbourne, Amy M.; Kim, Hyungin Myra] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48105 USA. [Kilbourne, Amy M.; Kim, Hyungin Myra] US Dept Vet Affairs, Ann Arbor Ctr Clin Management Res, Ann Arbor, MI 48105 USA. [Neumann, Mary Spink] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. [Waxmonsky, Jeanette; Thomas, Marshall] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80202 USA. [Bauer, Mark S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Pincus, Harold Alan] Columbia Univ, Sch Med, Dept Psychiat, New York, NY USA. RP Kilbourne, AM (reprint author), Univ Michigan, Dept Psychiat, 11H,2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM amykilbo@umich.edu RI Waxmonsky, Jeanette/L-4739-2013 FU NIMH NIH HHS [R01 MH 79994, R01 MH 74509] NR 5 TC 11 Z9 11 U1 0 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2012 VL 63 IS 3 BP 205 EP 207 DI 10.1176/appi.ps.201200032 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 917NV UT WOS:000302185600003 PM 22388527 ER PT J AU Copeland, LA Pugh, MJ Hicks, PB Noel, PH AF Copeland, Laurel Anne Pugh, Mary Jo Hicks, Paul B. Noel, Polly Hitchcock TI Use of Obesity Related Care by Psychiatric Patients SO PSYCHIATRIC SERVICES LA English DT Article ID HEALTH-SERVICES RESEARCH; SEVERE MENTAL-DISORDERS; QUALITY-OF-LIFE; ANTIPSYCHOTIC MEDICATIONS; WEIGHT-MANAGEMENT; VETERANS-AFFAIRS; CONTROLLED-TRIAL; SCHIZOPHRENIA; OVERWEIGHT; PATTERNS AB Objective: The objective of this study was to assess receipt of obesity care by patients with and without mental illness. Methods: The sample consisted of 254,051 obese primary care patients surviving through fiscal year (FY) 2006. Administrative data for Veterans Health Administration (VHA) patients who were obese in FY 2002 (body mass index >= 30) and received primary care in one of six selected VHA regions were included. Outcomes were receipt of obesity care and weight loss during FY 2002 FY 2006. Covariates included baseline mental illness (major depression, posttraumatic stress disorder, and substance use disorders; ICD-9-CM codes 290-311); psychotropic medications associated with weight gain; comorbidity; and demographic characteristics. Results: Most patients were male (95%), non-Hispanic white (80%), older than 50 (mean +/- SD=61 +/- 12) with comorbid hypertension (65%) and dyslipidemia (50%). One-fifth (20%) had mental illness, primarily depression (8%) or posttraumatic stress disorder (6%). Ten percent of the sample lost weight, and 7% gained >= 10% from baseline weight). Although one-third (34%) received obesity care during the study period, receipt of this care was more common among patients with psychiatric diagnoses (46% versus 31%). In multivariable analysis, psychiatric patients prescribed obesogenic psychotropic medications were more likely than other patients to receive obesity care (interaction effect). Conclusions: VITA efforts to help obese patients manage their weight appeared more common for patients prescribed obesogenic psychotropic medication, especially those with psychiatric diagnoses. The results of this study represent an unusual example in which psychiatric patients were relatively more likely to receive care addressing cardiometabolic risk factors. (Psychiatric Services 63:230-236, 2012; doi: 10.1176/appi.ps.201100221) C1 [Copeland, Laurel Anne] Cent Texas Vet Hlth Care Syst, Ctr Appl Hlth Res, Temple, TX 76502 USA. [Hicks, Paul B.] Cent Texas Vet Hlth Care Syst, Dept Med, Temple, TX 76502 USA. [Copeland, Laurel Anne] Scott & White Healthcare, Temple, TX USA. [Pugh, Mary Jo; Noel, Polly Hitchcock] S Texas Vet Hlth Care Syst, VERDICT Res, San Antonio, TX USA. [Pugh, Mary Jo] UT Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX USA. [Noel, Polly Hitchcock] UT Hlth Sci Ctr San Antonio, Div Clin Epidemiol, San Antonio, TX USA. RP Copeland, LA (reprint author), Cent Texas Vet Hlth Care Syst, Ctr Appl Hlth Res, 2102 Birdcreek Dr, Temple, TX 76502 USA. EM laurelacopeland@gmail.com OI Pugh, Mary Jo/0000-0003-4196-7763; Copeland, Laurel/0000-0002-9478-0209 FU U.S. Department of Veterans Affairs (VA), Health Services Research and Development Services [IIR-05-121]; Central Texas Veterans Health Care System; Scott and White Healthcare (Temple, Texas); VERDICT Research at South Texas Veterans Health Care System; University of Texas Health Science Center San Antonio FX This work was supported by the U.S. Department of Veterans Affairs (VA), Health Services Research and Development Services IIR-05-121, with additional support from Central Texas Veterans Health Care System, Scott and White Healthcare (Temple, Texas), VERDICT Research at the South Texas Veterans Health Care System, and the University of Texas Health Science Center San Antonio. The views expressed in this article are those of the authors and do not necessarily represent the views of the VA. NR 31 TC 6 Z9 6 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2012 VL 63 IS 3 BP 230 EP 236 DI 10.1176/appi.ps.201100221 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 917NV UT WOS:000302185600007 PM 22307880 ER PT J AU Yang, S Mulvey, EP Loughran, TA Hanusa, BH AF Yang, Suzanne Mulvey, Edward P. Loughran, Thomas A. Hanusa, Barbara H. TI Psychiatric Symptoms and Alcohol Use in Community Violence by Persons With a Psychotic Disorder or Depression SO PSYCHIATRIC SERVICES LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; RATING-SCALE; SUBSTANCE-ABUSE; MENTAL-DISORDER; RISK-ASSESSMENT; BEHAVIOR; SCHIZOPHRENIA; OTHERS; METAANALYSIS; MEDICATION AB Objective: Prior studies have shown a significant but modest association between mental disorders and violence and an increased risk in the presence of co-occurring substance use disorders. Categorical diagnoses, however, have limited utility when assessing dynamic risk state over time. This study used data from the MacArthur Violence Risk Assessment Study to examine the relationship of symptom levels and alcohol use to violence in repeated observations within two diagnostic groups. Methods: Participants with a primary categorical diagnosis of depression (N=386) or a psychotic disorder (N=201) were identified. Subscale scores for affective or positive symptoms from the Brief Psychiatric Rating Scale and self-reported alcohol consumption were tested in panel logistic models over five ten-week intervals for their concurrent and lagged relationship to violence. An interaction term between each type of symptom and alcohol use was also tested. Results: In models including the amount of alcohol consumed and symptom levels, a high level of affective symptoms was associated with violence during the next follow-up period only for participants with depression. There was a significant interaction between alcohol use and affective symptoms for participants with depression. Conclusions: The relationship of symptoms and alcohol use to community violence should be considered in the context of the individual's primary diagnosis. Further characterization of interactions between symptoms and substance use in relation to violent behavior may allow for more effective assessment of risk state and interventions for violence prevention. (Psychiatric Services 63:262-269, 2012; doi: 10.1176/appi.ps.201100354) C1 [Yang, Suzanne] VA Pittsburgh Healthcare Syst, Vet Integrated Serv Network VISN Mental Illness R, Pittsburgh, PA 15206 USA. [Yang, Suzanne] Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. [Yang, Suzanne] Univ Pittsburgh, Law & Psychiat Program, Pittsburgh, PA 15260 USA. [Mulvey, Edward P.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Loughran, Thomas A.] Univ Maryland, Dept Criminol, College Pk, MD 20742 USA. [Hanusa, Barbara H.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Hanusa, Barbara H.] VA Pittsburgh Healthcare Syst, VISN MIRECC 4, Pittsburgh, PA 15206 USA. RP Yang, S (reprint author), VA Pittsburgh Healthcare Syst, Vet Integrated Serv Network VISN Mental Illness R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM yangs@upmc.edu FU National Institute of Mental Health [T32 MH16804]; U.S. Department of Veterans Affairs (VA), Office of Academic Affiliations FX During the preparation of the manuscript, Dr. Yang was supported by grant T32 MH16804 from the National Institute of Mental Health and by the U.S. Department of Veterans Affairs (VA), Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment. Contents do not represent the views of the VA or the U.S. government. Dr. Yang thanks Kevin Kim, Ph.D., Candice Odgers, Ph.D., and Ada Youk, Ph.D., for valuable advice during data analysis and Bruno Falissard, M.D., Ph.D., for insightful comments on the manuscript. NR 40 TC 3 Z9 3 U1 2 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2012 VL 63 IS 3 BP 262 EP 269 DI 10.1176/appi.ps.201100354 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 917NV UT WOS:000302185600012 PM 22388531 ER PT J AU Chang, G Weiss, A Kosowsky, JM Orav, EJ Smallwood, JA Rauch, SL AF Chang, Grace Weiss, Anthony Kosowsky, Joshua M. Orav, Endel John Smallwood, Jennifer A. Rauch, Scott L. TI Characteristics of Adult Psychiatric Patients With Stays of 24 Hours or More in the Emergency Department SO PSYCHIATRIC SERVICES LA English DT Article ID CARE AB Objective: This study identified characteristics of adult psychiatric patients who remained for 24 or more hours in the emergency departments of general hospitals in Massachusetts. Methods: Data were collected starting in June 2008 on a prospective cohort of 1,076 patients who presented for emergency psychiatric evaluation at one of five hospitals. Results: A total of 90 patients (8%) stayed 24 or more hours (median=31 hours). More than 90% (N=1,018) of all patients had health insurance. Characteristics associated with extended stays included homelessness, transfer to another hospital, public insurance, and use of restraints or sitters (p<.05). The two academic medical centers had higher proportions of extended-stay patients than the three community hospitals (12% and 15% versus 1%, 7%, and 7%, respectively; p<.001). Conclusions: Despite overall high rates of health insurance coverage, publicly insured patients waited longer than those with private insurance. Future reforms of Massachusetts' mandatory health insurance program should consider treatment capacity as well. (Psychiatric Services 63:283-286, 2012; doi: 10.1176/appi.ps.201000563) C1 [Chang, Grace] Boston Hlth Care Syst, Dept Vet Affairs, Dept Psychiat, Brockton, MA 02301 USA. [Weiss, Anthony] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kosowsky, Joshua M.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Orav, Endel John] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Smallwood, Jennifer A.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. [Chang, Grace; Weiss, Anthony; Kosowsky, Joshua M.; Orav, Endel John; Rauch, Scott L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Chang, G (reprint author), Boston Hlth Care Syst, Dept Vet Affairs, Dept Psychiat, 940 Belmont St, Brockton, MA 02301 USA. EM grace.chang2@va.gov FU Partners Psychiatry and Mental Health Division of Health Services Research from National Institute on Alcohol Abuse and Alcoholism [K-24-AA000289] FX This study was supported by the Partners Psychiatry and Mental Health Division of Health Services Research and grant K-24-AA000289 to Dr. Chang from the National Institute on Alcohol Abuse and Alcoholism. The authors thank Kenneth J. Sklar, Ed.D. NR 11 TC 10 Z9 10 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAR PY 2012 VL 63 IS 3 BP 283 EP 286 DI 10.1176/appi.ps.201000563 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 917NV UT WOS:000302185600017 PM 22267250 ER PT J AU Dubovsky, AN Arvikar, S Stern, TA Axelrod, L AF Dubovsky, Amelia N. Arvikar, Sheila Stern, Theodore A. Axelrod, Lloyd TI The Neuropsychiatric Complications of Glucocorticoid Use: Steroid Psychosis Revisited SO PSYCHOSOMATICS LA English DT Review ID RECEIVING CORTICOSTEROID-THERAPY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; WITHDRAWAL SYNDROME; MAJOR DEPRESSION; CUSHINGS-DISEASE; MOOD DISORDERS; INDUCED MANIA; PREDNISONE; MEMORY; COGNITION AB Background: Glucocorticoids are widely prescribed for a variety of diseases and are known to cause neuropsychiatric as well as somatic side effects. Objective: This article will review the incidence, clinical characteristics, course, and treatment of neuropsychiatric effects of glucocorticoids. Methods: We performed a literature review of the neuropsychiatric complications of glucocorticoids using the PubMed database. Results: The neuropsychiatric effects of glucocorticoids involve affective, behavioral, and cognitive manifestations. Serious neuropsychiatric effects occur in about 6% of patients who receive steroids. Although the effects of glucocorticoids are unpredictable, the administered dose is the most significant risk factor for the development of neuropsychiatric symptoms. Dosage reduction typically results in clinical recovery. Although evidence from controlled trials is sparse, administration of antipsychotics or mood stabilizers may be beneficial in the prevention and treatment of neuropsychiatric effects of steroids. Conclusion: The neuropsychiatric effects of glucocorticoids are more diverse than the often-misleading term "steroid psychosis" suggests. This label should be limited to those patients who are truly psychotic, and specific designations applied to patients with other effects. The adverse neuropsychiatric effects of glucocorticoids remain poorly characterized in the literature (which consists largely of case reports and case series). Reliable risk factors (other than dose) that identify individuals at risk are lacking; guidelines for the prevention of neuropsychiatric effects are not evidence-based. Further controlled clinical studies are needed to elucidate the optimal management of glucocorticoid-induced neuropsychiatric symptoms. (Psychosomatics 2012; 53:103-115) C1 [Dubovsky, Amelia N.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Arvikar, Sheila] Dept Rheumatol Allergy & Immunol, Boston, MA USA. [Axelrod, Lloyd] Massachusetts Gen Hosp, Dept Med, Div Endocrine, Boston, MA 02114 USA. RP Dubovsky, AN (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 815,55 Fruit St, Boston, MA 02114 USA. EM ADUBOVSKY@PARTNERS.ORG NR 90 TC 36 Z9 38 U1 2 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAR-APR PY 2012 VL 53 IS 2 BP 103 EP 115 PG 13 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 915BO UT WOS:000301998100001 PM 22424158 ER PT J AU Wodchis, WP Bhatia, RS Leblanc, K Meshkat, N Morra, D AF Wodchis, Walter P. Bhatia, R. Sacha Leblanc, Kori Meshkat, Nazanin Morra, Dante TI A Review of the Cost of Atrial Fibrillation SO VALUE IN HEALTH LA English DT Review DE atrial fibrillation; cost analysis; cost of illness; direct cost; systematic review ID CATHETER ABLATION; UNITED-STATES; ANTIARRHYTHMIC-DRUGS; ECONOMIC-EVALUATION; STROKE PREVENTION; WARFARIN THERAPY; RHYTHM-CONTROL; RISK-FACTORS; CARE; ANTICOAGULATION AB Objectives: To systematically review and synthesize the literature on the costs of atrial fibrillation (AF) with attention to study design and costing methods, geography, and intervention approaches. Methods: A systematic search for previously published studies reporting the costs for AF patients was conducted. Data were analyzed in three steps: first by evaluating overall system costs; second by evaluating the relative contribution of specific cost components; and third by examining variations across study designs, across primary treatment approach, and by geography. Finally, a specific review of the treatment costs associated with anticoagulation treatment was examined given the clinical importance and attention given to these costs in the literature. Results: The literature search resulted in 115 articles. On review of the abstracts or full text of these articles, 21 articles met all study criteria and reported on health system AF-related direct costs. A further six articles focused exclusively on anticoagulation costs for patients with AF. The overall average annual system cost across 27 esti-mates obtained from the literature was $5450 (SD = $3624) in 2010 Canadian dollars and ranged from a low of $1,632 to a high of $21,099. About one-third of these costs could be attributed to anticoagulation management. The largest cost component was acute care, followed by outpatient and physician and then medication-related costs. Conclusion: AF-related medical costs are high, reflecting resource-intensive and long-term treatments including anticoagulation treatment. These costs, accompanied with increasing prevalence, justify increased attention to the management of patients with AF. Future studies of AF cost should ensure a broad assessment of the incremental direct medical and societal cost associated with this diagnosis. C1 [Wodchis, Walter P.] Univ Toronto, Fac Med, Toronto, ON M5T 3M6, Canada. [Wodchis, Walter P.] Toronto Rehabil Inst, Toronto, ON, Canada. [Bhatia, R. Sacha] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Leblanc, Kori] Univ Toronto, Ctr Innovat & Complex Care, Univ Hlth Network, Fac Pharm, Toronto, ON, Canada. [Leblanc, Kori] Univ Toronto, Dept Pharm, Toronto, ON, Canada. [Meshkat, Nazanin; Morra, Dante] Univ Toronto, Dept Med, Toronto, ON, Canada. [Meshkat, Nazanin] Univ Hlth Network, Div Emergency Med, Toronto, ON, Canada. [Morra, Dante] Univ Hlth Network, Ctr Innovat Complex Care, Toronto, ON, Canada. RP Wodchis, WP (reprint author), Univ Toronto, Fac Med, 155 Coll St,4th Floor, Toronto, ON M5T 3M6, Canada. EM walter.wodchis@utoronto.ca FU Boehringer Ingelheim FX The Center for Innovation in Complex Care is supported in part by Boehringer Ingelheim. The study was carried out independently of the funder. The publication of this study's results was not reviewed by or contingent on the approval or censorship of any affiliated sponsor. NR 55 TC 28 Z9 28 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 EI 1524-4733 J9 VALUE HEALTH JI Value Health PD MAR-APR PY 2012 VL 15 IS 2 BP 240 EP 248 DI 10.1016/j.jval.2011.09.009 PG 9 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 914DZ UT WOS:000301930600004 PM 22433754 ER PT J AU Renaud, B Brun-Buisson, C Santin, A Coma, E Noyez, C Fine, MJ Yealy, DM Labarere, J AF Renaud, Bertrand Brun-Buisson, Christian Santin, Aline Coma, Eva Noyez, Cecile Fine, Michael J. Yealy, Donald M. Labarere, Jose TI Outcomes of Early, Late, and No Admission to the Intensive Care Unit for Patients Hospitalized with Community-acquired Pneumonia SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID INFECTIOUS-DISEASES-SOCIETY; PREDICTION RULE; EMERGENCY-DEPARTMENT; CONTROLLED-TRIAL; SEVERITY-INDEX; RISK-FACTORS; VALIDATION; GUIDELINES; MORTALITY; CRITERIA AB Objectives: The objective was to compare outcomes associated with early, late, and no admission to the intensive care unit (ICU) for patients hospitalized with community-acquired pneumonia (CAP). Methods: This was a post hoc analysis of the original data from the Emergency Department Community-Acquired Pneumonia (EDCAP) and Pneumocom-1 prospective multicenter cohort studies of adult patients hospitalized with CAP. Propensity scoreadjusted analysis was used to compare 28-day mortality and hospital length of stay (LOS) for 199, 144, and 2,215 patients with early (i.e., ICU admission on the day of emergency department [ED] presentation), late, and no ICU admission. Results: Unadjusted 28-day mortality rates were 13.1, 19.4, and 5.7% for early, late, and no ICU admissions, respectively (p < 0.001). After adjusting for quintile of propensity score, the odds of 28-day mortality were higher for late ICU admissions relative to early ICU admissions (odds ratio [OR] = 2.63; 95% confidence interval [CI] = 1.42 to 4.90), and no ICU admissions (OR = 3.40; 95% CI = 2.11 to 5.48), but did not differ between early and no ICU admissions (OR = 1.29; 95% CI = 0.79 to 2.09). The median hospital LOS was 10 days for early (interquartile range [IQR] = 7 to 18), 15 days for late (IQR 9 to 23), and 6 days (IQR 4 to 9) for no ICU admissions (p < 0.001). Conclusions: This study suggests that late but not early admission to the ICU is associated with higher 28-day mortality for patients hospitalized with CAP. Patients admitted to the ICU have longer hospital LOS in comparison to those managed on the wards, particularly if they are admitted late to the ICU. ACADEMIC EMERGENCY MEDICINE 2012; 19:## (C) 2012 by the Society for Academic Emergency Medicine C1 [Renaud, Bertrand; Santin, Aline] Grp Hosp Henri Mondor Albert Chenevier, AP HP, Serv Urgence, Creteil, France. [Renaud, Bertrand; Brun-Buisson, Christian; Santin, Aline] Univ Paris 12, Fac Med, Creteil, France. [Coma, Eva] Hosp Duran & Reynals, Inst Catala Oncol, Serv Atencio Continuada USAC, Barcelona 08907, Spain. [Noyez, Cecile] Ctr Hosp Montauban, Emergency Dept, Montauban, France. [Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Fine, Michael J.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Yealy, Donald M.] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA USA. [Labarere, Jose] CHU Grenoble, Qual Care Unit, F-38043 Grenoble, France. [Labarere, Jose] Univ Grenoble 1, TIMC UMR CNRS 5525, Grenoble, France. RP Renaud, B (reprint author), Grp Hosp Henri Mondor Albert Chenevier, AP HP, Serv Urgence, Creteil, France. EM bertrand.renaud@hmn.aphp.fr RI Labarere, Jose/N-1688-2014; OI Labarere, Jose/0000-0001-7621-6586 FU Direction de la Recherche Clinique d'Ile de France [AOM 89-145]; Departement de la Formation Continue des Medecins de l'Assistance Publique des Hopitaux de Paris (AP-HP); l'ARMUR (Association de Recherche en Medecine d'Urgence, Henri Mondor, Creteil) France; AQUARE (Association pour la QUAlite, la Recherche et l'Enseignement a l'Hopital Saint-Joseph (Paris)); GlaxoSmithKline France; Direction de la Recherche Clinique du Centre Hospitalier Universitaire de Grenoble FX This study was funded by the Direction de la Recherche Clinique d'Ile de France as part of the Programme Hospitalier de Recherche Clinique (Grant No. AOM 89-145). B. Renaud was supported by the Departement de la Formation Continue des Medecins de l'Assistance Publique des Hopitaux de Paris (AP-HP), by l'ARMUR (Association de Recherche en Medecine d'Urgence, Henri Mondor, Creteil) France; by AQUARE (Association pour la QUAlite, la Recherche et l'Enseignement a l'Hopital Saint-Joseph (Paris)); and by GlaxoSmithKline France. J. Labarere was supported by the Direction de la Recherche Clinique du Centre Hospitalier Universitaire de Grenoble. NR 36 TC 7 Z9 8 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 2012 VL 19 IS 3 BP 294 EP 303 DI 10.1111/j.1553-2712.2012.01301.x PG 10 WC Emergency Medicine SC Emergency Medicine GA 912EE UT WOS:000301776700007 PM 22435862 ER PT J AU Ikonomovic, MD Abrahamson, EE Price, JC Hamilton, RL Mathis, CA Paljug, WR Debnath, ML Cohen, AD Mizukami, K DeKosky, ST Lopez, OL Klunk, WE AF Ikonomovic, Milos D. Abrahamson, Eric E. Price, Julie C. Hamilton, Ronald L. Mathis, Chester A. Paljug, William R. Debnath, Manik L. Cohen, Anne D. Mizukami, Katsuyoshi DeKosky, Steven T. Lopez, Oscar L. Klunk, William E. TI Early AD pathology in a [C-11]PiB-negative case: a PiB-amyloid imaging, biochemical, and immunohistochemical study SO ACTA NEUROPATHOLOGICA LA English DT Article DE Alzheimer's disease; Brain amyloidosis; Pittsburgh Compound B; Plaques; Imaging ID PITTSBURGH COMPOUND-B; POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS-DISEASE; SENILE PLAQUES; NEUROPATHOLOGIC ASSESSMENT; NEUROFIBRILLARY TANGLES; REGIONAL-DISTRIBUTION; BETA PROTEIN; PET; BRAIN AB Amyloid-beta (A beta) deposits are detectable in the brain in vivo using positron emission tomography (PET) and [C-11]-labeled Pittsburgh Compound B ([C-11]PiB); however, the sensitivity of this technique is not well understood. In this study, we examined A beta pathology in an individual who had clinical diagnoses of probable dementia with Lewy bodies and possible Alzheimer's disease (AD) but with no detectable [C-11]PiB PET retention ([C-11]PiB(-)) when imaged 17 months prior to death. Brain samples were processed in parallel with region-matched samples from an individual with a clinical diagnosis of probable AD and a positive [C-11]PiB PET scan ([C-11]PiB(+)) when imaged 10 months prior to death. In the [C-11]PiB(-) case, A beta plaques were sparse, occupying less than 2% cortical area, and were weakly labeled with 6-CN-PiB, a highly fluorescent derivative of PiB. In contrast, A beta plaques occupied up to 12% cortical area in the [C-11]PiB(+) case, and were intensely labeled with 6-CN-PIB. The [C-11]PiB(-) case had low levels of [H-3]PiB binding (<100 pmol/g) and A beta 1-42 (<500 pmol/g) concentration except in the frontal cortex where A beta 1-42 values (788 pmol/g) approached cortical values in the [C-11]PiB(+) case (800-1,700 pmol/g). In several cortical regions of the [C-11]PiB(-) case, A beta 1-40 levels were within the range of cortical A beta 1-40 values in the [C-11]PiB(+) case. Antemortem [C-11]PiB DVR values correlated well with region-matched postmortem measures of A beta 1-42 and A beta 1-40 in the [C-11]PiB(+), and with A beta 1-42 only in the [C-11]PiB(-) case. The low ratios of [H-3]PiB binding levels to Ab concentrations and 6-CN-PiB to Ab plaque loads in the [C-11]PiB(-) case indicate that Ab pathology in the brain may be associated with low or undetectable levels of [C-11]PiB retention. Studies in greater numbers of [C-11]PiB PET autopsy cases are needed to define the Ab concentration and [H-3]PiB binding levels required to produce a positive [C-11]PiB PET signal. C1 [Ikonomovic, Milos D.; Abrahamson, Eric E.; Paljug, William R.; Lopez, Oscar L.; Klunk, William E.] Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh, PA 15213 USA. [Ikonomovic, Milos D.; Debnath, Manik L.; Cohen, Anne D.; Klunk, William E.] Univ Pittsburgh, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. [Price, Julie C.; Mathis, Chester A.] Univ Pittsburgh, Dept Radiol, Sch Med, Pittsburgh, PA 15213 USA. [Hamilton, Ronald L.] Univ Pittsburgh, Dept Neuropathol, Sch Med, Pittsburgh, PA 15213 USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Mizukami, Katsuyoshi] Univ Tsukuba, Inst Clin Med, Dept Psychiat, Tsukuba, Ibaraki 305, Japan. [DeKosky, Steven T.] Univ Virginia, Sch Med, Off Dean, Charlottesville, VA 22908 USA. [DeKosky, Steven T.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA. RP Ikonomovic, MD (reprint author), Univ Pittsburgh, Dept Neurol, Sch Med, 200 Lothrop St,BST S521, Pittsburgh, PA 15213 USA. EM ikonomovicmd@upmc.edu OI Klunk, William/0000-0001-5512-0251 FU National Institutes of Health [AG025204, AG025516, AG005133, AG014449, AG033042]; GE Healthcare; Phillip V. and Anna S. Brown Foundation; Snee-Reinhardt Charitable Foundation FX We gratefully acknowledge the technical expertise of Suganya Srinivasan, Lan Shao, Hui Wang, and Jonette Werley. We thank the staff at the University of Pittsburgh Alzheimer's Disease Research Center and PET facility for their efforts in conducting and analyzing these studies. We are indebted to our subjects and their families for the selfless contributions that made this work possible. This work was supported by the National Institutes of Health grants AG025204, AG025516, AG005133, AG014449, and AG033042, GE Healthcare, The Phillip V. and Anna S. Brown Foundation, and the Snee-Reinhardt Charitable Foundation. NR 52 TC 41 Z9 41 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAR PY 2012 VL 123 IS 3 BP 433 EP 447 DI 10.1007/s00401-012-0943-2 PG 15 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 913EJ UT WOS:000301856300009 PM 22271153 ER PT J AU Drye, LT Ismail, Z Porsteinsson, AP Rosenberg, PB Weintraub, D Marano, C Pelton, G Frangakis, C Rabins, PV Munro, CA Meinert, CL Devanand, DP Yesavage, J Mintzer, JE Schneider, LS Pollock, BG Lyketsos, CG AF Drye, Lea T. Ismail, Zahinoor Porsteinsson, Anton P. Rosenberg, Paul B. Weintraub, Daniel Marano, Christopher Pelton, Gregory Frangakis, Constantine Rabins, Peter V. Munro, Cynthia A. Meinert, Curtis L. Devanand, D. P. Yesavage, Jerome Mintzer, Jacobo E. Schneider, Lon S. Pollock, Bruce G. Lyketsos, Constantine G. CA CitAD Res Grp TI Citalopram for agitation in Alzheimer's disease: Design and methods SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer dementia; Citalopram; Agitation; Randomized trial ID PLACEBO-CONTROLLED TRIAL; NEUROPSYCHIATRIC-SYMPTOMS; ELDERLY-PATIENTS; NURSING-HOME; DOUBLE-BLIND; BEHAVIORAL DISTURBANCES; SEROTONIN TRANSPORTER; DEMENTED PATIENTS; DEPRESSION; ASSOCIATION AB Background: Agitation is one of the most common neuropsychiatric symptoms of Alzheimer's disease (AD), and is associated with serious adverse consequences for patients and caregivers. Evidence-supported treatment options for agitation are limited. The citalopram for agitation in Alzheimer's disease (CitAD) study was designed to evaluate the potential of citalopram to ameliorate these symptoms. Methods: CitAD is a randomized, double-masked, placebo-controlled multicenter clinical trial, with two parallel treatment groups assigned in a 1:1 ratio and randomization stratified by clinical center. The study included eight recruiting clinical centers, a chair's office, and a coordinating center located in university settings in the United States and Canada. A total of 200 individuals having probable AD with clinically significant agitation and without major depression were recruited for this study. Patients were randomized to receive citalopram (target dose of 30 mg/d) or matching placebo. Caregivers of patients in both treatment groups received a structured psychosocial therapy. Agitation was compared between treatment groups using the NeuroBehavioral Rating Scale and the AD Cooperative Study- Clinical Global Impression of Change, which are the primary outcomes. Functional performance, cognition, caregiver distress, and rates of adverse and serious adverse events were also measured. Conclusion: The authors believe the design elements in CitAD are important features to he included in trials assessing the safety and efficacy of psychotropic medications for clinically significant agitation in AD. (C) 2012 The Alzheimer's Association. All rights reserved. C1 [Drye, Lea T.; Frangakis, Constantine; Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Drye, Lea T.; Frangakis, Constantine; Meinert, Curtis L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Ismail, Zahinoor; Pollock, Bruce G.] Univ Toronto, Div Geriatr Psychiat, Toronto, ON, Canada. [Porsteinsson, Anton P.] Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. [Rosenberg, Paul B.; Marano, Christopher; Rabins, Peter V.; Munro, Cynthia A.; Lyketsos, Constantine G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Rosenberg, Paul B.; Marano, Christopher; Rabins, Peter V.; Munro, Cynthia A.; Lyketsos, Constantine G.] Johns Hopkins Bayview Med Ctr, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD USA. [Weintraub, Daniel] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Pelton, Gregory; Devanand, D. P.] Columbia Univ, Div Geriatr Psychiat, New York State Psychiat Inst, New York, NY USA. [Pelton, Gregory; Devanand, D. P.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Yesavage, Jerome] Stanford Univ, Sch Med,Dept Vet Affairs, Med Res Serv Vet Affairs Palo Alto Hlth Care Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Palo Alto, CA 94304 USA. [Yesavage, Jerome] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Mintzer, Jacobo E.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Mintzer, Jacobo E.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Schneider, Lon S.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Schneider, Lon S.] Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90033 USA. RP Drye, LT (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. EM ldrye@jhsph.edu OI Drye, Lea/0000-0002-2964-1878 FU National Institute on Aging; National Institute of Mental Health [R01AG031348] FX Grant funding: National Institute on Aging and National Institute of Mental Health, R01AG031348. NR 59 TC 20 Z9 20 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD MAR PY 2012 VL 8 IS 2 BP 121 EP 130 DI 10.1016/j.jalz.2011.01.007 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 914ZE UT WOS:000301991600005 PM 22301195 ER PT J AU Funke, M Zhao, ZW Xu, Y Chun, J Tager, AM AF Funke, Manuela Zhao, Zhenwen Xu, Yan Chun, Jerold Tager, Andrew M. TI The Lysophosphatidic Acid Receptor LPA(1) Promotes Epithelial Cell Apoptosis after Lung Injury SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE pulmonary fibrosis; apoptosis; epithelial cells, lysophosphatidic acid; LPA(1) ID IDIOPATHIC PULMONARY-FIBROSIS; GROWTH-FACTOR BETA(1); MESSENGER-RNA; EXPRESSION; ANOIKIS; ACTIVATION; BLEOMYCIN; MICE; DEATH; FIBROBLASTS AB Increased epithelial cell apoptosis in response to lung injury has been implicated in the development of idiopathic pulmonary fibrosis (IPF), but the molecular pathways promoting epithelial cell apoptosis in this disease have yet to be fully identified. Lysophosphatidic acid (LPA), which we have previously demonstrated to mediate bleomycin lung injury-induced fibroblast recruitment and vascular leak in mice and fibroblast recruitment in patients with IPF, is an important regulator of survival and apoptosis in many cell types. We now show that LPA signaling through its receptor LPA(1) promotes epithelial cell apoptosis induced by bleomycin injury. The number of apoptotic cells present in the alveolar and bronchial epithelia of LPA(1)-deficient mice was significantly reduced compared with wild-type mice at Day 3 after bleomycin challenge, as was lung caspase3 activity. Consistent with these in vivo results, we found that LPA signaling through LPA(1) induced apoptosis in normal human bronchial epithelial cells in culture. LPA-LPA(1) signaling appeared to specifically mediate anoikis, the apoptosis of anchorage-dependent cells induced by their detachment. Similarly, LPA negatively regulated attachment of R3/1 rat alveolar epithelial cell line cells. In contrast, LPA signaling through LPA(1) promoted the resistance of lung fibroblasts to apoptosis, which has also been implicated in IPF. The ability of LPA-LPA(1) signaling to promote epithelial cell apoptosis and fibroblast resistance to apoptosis may therefore contribute to the capacity of this signaling pathway to regulate the development of pulmonary fibrosis after lung injury. C1 [Zhao, Zhenwen; Xu, Yan] Indiana Univ Sch Med, Dept Obstet & Gynecol, Indianapolis, IN USA. [Chun, Jerold] Scripps Res Inst, Dept Mol Biol, Dorris Neurosci Ctr, La Jolla, CA 92037 USA. [Funke, Manuela; Tager, Andrew M.] Harvard Univ, Pulm & Crit Care Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Funke, Manuela; Tager, Andrew M.] Harvard Univ, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Tager, AM (reprint author), Harvard Univ, Pulm & Crit Care Unit, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp,Med Sch, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM amtager@partners.org FU NIH [R01-HL095732, R01-HL108975, R01-CA095042]; Pulmonary Fibrosis Foundation; Coalition for Pulmonary Fibrosis/American Thoracic Society; Nirenberg Center for Advanced Lung Disease; Swiss National Foundation; Swiss Society of Pulmonology; Fondation pour la Recherche et le Traitement des Maladies Respiratoires; [NIH-HD050685]; [NIH-DA019674] FX This work was supported by NIH R01-HL095732 and R01-HL108975, a Pulmonary Fibrosis Foundation grant, a Coalition for Pulmonary Fibrosis/American Thoracic Society grant, and a Nirenberg Center for Advanced Lung Disease Grant (A.M.T); by a Swiss National Foundation grant, a Swiss Society of Pulmonology grant, and a grant from the Fondation pour la Recherche et le Traitement des Maladies Respiratoires (M.F.); by NIH grant R01-CA095042 (Y.X.); and by grants NIH-HD050685 and NIH-DA019674 (J.C.). NR 50 TC 46 Z9 48 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 2012 VL 46 IS 3 BP 355 EP 364 DI 10.1165/rcmb.2010-0155OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 901HD UT WOS:000300953800010 PM 22021336 ER PT J AU Pankratz, N Beecham, GW DeStefano, AL Dawson, TM Doheny, KF Factor, SA Hamza, TH Hung, AY Hyman, BT Ivinson, AJ Krainc, D Latourelle, JC Clark, LN Marder, K Martin, ER Mayeux, R Ross, OA Scherzer, CR Simon, DK Tanner, C Vance, JM Wszolek, ZK Zabetian, CP Myers, RH Payami, H Scott, WK Foroud, T AF Pankratz, Nathan Beecham, Gary W. DeStefano, Anita L. Dawson, Ted M. Doheny, Kimberly F. Factor, Stewart A. Hamza, Taye H. Hung, Albert Y. Hyman, Bradley T. Ivinson, Adrian J. Krainc, Dmitri Latourelle, Jeanne C. Clark, Lorraine N. Marder, Karen Martin, Eden R. Mayeux, Richard Ross, Owen A. Scherzer, Clemens R. Simon, David K. Tanner, Caroline Vance, Jeffery M. Wszolek, Zbigniew K. Zabetian, Cyrus P. Myers, Richard H. Payami, Haydeh Scott, William K. Foroud, Tatiana CA PD GWAS Consortium TI Meta-analysis of Parkinson's Disease: Identification of a novel locus, RIT2 SO ANNALS OF NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN; RISK-FACTORS; CALMODULIN; SNCA; SUSCEPTIBILITY; HAPLOTYPES; VARIANTS; SEQUENCE; GENETICS AB Objective: Genome-wide association (GWAS) methods have identified genes contributing to Parkinson's disease (PD); we sought to identify additional genes associated with PD susceptibility. C1 [Pankratz, Nathan; Foroud, Tatiana] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Beecham, Gary W.; Martin, Eden R.; Vance, Jeffery M.; Scott, William K.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [DeStefano, Anita L.; Latourelle, Jeanne C.; Myers, Richard H.] Boston Univ, Sch Med, Boston, MA 02118 USA. [DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Dawson, Ted M.; Doheny, Kimberly F.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Factor, Stewart A.] Emory Univ, Atlanta, GA 30322 USA. [Hamza, Taye H.; Payami, Haydeh] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Hung, Albert Y.; Hyman, Bradley T.; Krainc, Dmitri] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hyman, Bradley T.; Ivinson, Adrian J.; Scherzer, Clemens R.] Harvard Univ, Sch Med, Biomarker Program, Harvard NeuroDiscovery Ctr, Boston, MA USA. [Clark, Lorraine N.; Marder, Karen; Mayeux, Richard] Columbia Univ, Coll Phys & Surg, Sch Med, New York, NY USA. [Ross, Owen A.; Wszolek, Zbigniew K.] Mayo Clin, Jacksonville, FL 32224 USA. [Scherzer, Clemens R.] Partners Parkinson Ctr, Boston, MA USA. [Scherzer, Clemens R.] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Simon, David K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Tanner, Caroline] Parkinsons Inst, Sunnyvale, CA USA. [Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Zabetian, Cyrus P.] Univ Washington, Seattle, WA 98195 USA. RP Foroud, T (reprint author), Indiana Univ Sch Med, 410 W 10th St HS 4000, Indianapolis, IN 46202 USA. EM tforoud@iupui.edu RI Kowall, Neil/G-6364-2012; Haines, Jonathan/C-3374-2012; Ross, Owen/D-7573-2013; Ottman, Ruth/O-2371-2013; OI Kowall, Neil/0000-0002-6624-0213; Latourelle, Jeanne/0000-0002-4218-9572; Hirschberger, Johannes/0000-0002-1382-6114; Myers, Richard/0000-0002-8365-2674; Zabetian, Cyrus/0000-0002-7739-4306; Goldwurm, Stefano/0000-0002-1651-567X FU Indiana CTSI CRC [M01RR00750/ RR025761, R01NS36960, P50NS39764, R01NS064155, U10NS44482, 1RC2NS070276, R01NS057567, P50NS072187, IH NS36630, UL1 RR024156, NS050487, R01NS060113, U24AG026395, 1I01BX000531, R01NS36711]; Harvard NeuroDiscovery Center; Michael J. Fox Foundation; Michael J. Fox Foundation Edmond J Safra Michael J Fox Foundation Global Genetic Consortium Initiative; Bumpus Foundation; Robert P. and Judith N. Goldberg Foundation; National Parkinson Foundation; Parkinson's Disease Foundation; Mayo Clinic Florida (MCF) Research Committee [90052018, 90052030]; Dystonia Medical Research Foundation; National Institute on Aging [P30 AG19610]; Arizona Department of Health Services [211002]; Arizona Biomedical Research Commission [4001, 0011, 05-901]; Prescott Family Initiative of the Michael J. Fox Foundation for Parkinson's Research; Harvard Brain Tissue Resource Center; PHS [R24 MH 068855]; Human Brain and Spinal Fluid Resource Center VA West Los Angeles Healthcare Center; NINDS/NIMH, National Multiple Sclerosis Society, Department of Veterans; [R01CA141668]; [R01NS37167]; [R01NS065070]; [R56NS037167]; [90052031/PAU #90052] FX This project was supported by R01CA141668 (TF), R01NS37167 (TF), R01NS065070 (CPZ), R56NS037167 (TF), Indiana CTSI CRC (M01RR00750/ RR025761 - TF), R01NS36960 (HP), P50NS39764 (WKS), R01NS064155 (CRS), U10NS44482 (DS), 1RC2NS070276 (ZKW, OAR), R01NS057567 (ZKW), P50NS072187 (ZKW, OAR), IH NS36630 (KSM), UL1 RR024156 (KSM), NS050487 (LNC), R01NS060113 (LNC), U24AG026395 (RM), 1I01BX000531 (CPZ), R01NS36711 (RHM), Harvard NeuroDiscovery Center (CRS), The Michael J. Fox Foundation (CRS), The Michael J. Fox Foundation Edmond J Safra Michael J Fox Foundation Global Genetic Consortium Initiative (HP), Bumpus Foundation (RHM), Robert P. and Judith N. Goldberg Foundation (RHM), National Parkinson Foundation; Parkinson's Disease Foundation (KSM, LNC, DK, AYH) Joseph R. Mazzulli and Grace Bwala (DK, AYH), Mayo Clinic Florida (MCF) Research Committee CR programs (MCF #90052018 and MCF #90052030) (ZKW), and the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch (MCF #90052031/PAU #90052) (ZKW, OAR), and Dystonia Medical Research Foundation (ZKW).; Control samples and clinical data were provided from the National Cell Repository for Alzheimer's Disease (U24 AG021886; TF) and the NINDS Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds). PD and control brain samples provided by the Sun Health Research Institute in Sun City, Arizona, which is supported by the National Institute on Aging (P30 AG19610 Arizona Alzheimer's Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer's Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011 and 05-901 to the Arizona Parkinson's Disease Consortium) and the Prescott Family Initiative of the Michael J. Fox Foundation for Parkinson's Research; the Harvard Brain Tissue Resource Center, which is supported in part by PHS grant number R24 MH 068855, and the Human Brain and Spinal Fluid Resource Center VA West Los Angeles Healthcare Center, 11301 Wilshire Blvd. Los Angeles, CA 90073, which is sponsored by NINDS/NIMH, National Multiple Sclerosis Society, Department of Veterans. NR 25 TC 102 Z9 102 U1 0 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2012 VL 71 IS 3 BP 370 EP 384 DI 10.1002/ana.22687 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 914BD UT WOS:000301922800012 PM 22451204 ER PT J AU Lichtman, SM Hurria, A Cirrincione, CT Seidman, AD Winer, E Hudis, C Cohen, HJ Muss, HB AF Lichtman, S. M. Hurria, A. Cirrincione, C. T. Seidman, A. D. Winer, E. Hudis, C. Cohen, H. J. Muss, H. B. CA Canc Leukemia Grp B TI Paclitaxel efficacy and toxicity in older women with metastatic breast cancer: combined analysis of CALGB 9342 and 9840 SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; elderly; geriatric oncology; geriatrics; neurotoxicity; paclitaxel ID ELDERLY-PATIENTS; ADJUVANT CHEMOTHERAPY; 1ST-LINE CHEMOTHERAPY; RANDOMIZED-TRIAL; EXPERIENCE; ONCOLOGY; TABLES; LIFE; AGE AB Background: Two Cancer and Leukemia Group B (CALGB) studies were utilized to determine the efficacy and tolerability of paclitaxel (Taxol) in older patients with metastatic breast cancer. Patients and methods: CALGB 9840 evaluated weekly paclitaxel (80 mg/m(2)) versus paclitaxel every 3 weeks (175 mg/m(2)); CALGB 9342 evaluated three doses of paclitaxel as follows: 175, 210 and 250 mg/m(2) each over 3 h every 3 weeks. Of the 1048 patients, paclitaxel was used first line in 57%. The groups: (i) <55 years (45%), (ii) 55-64 years (29%), and (iii) >= 65 years (26%). Results: Tumor response was also similar among age groups. First-line therapy (P = 0.0001) and better performance status (PS) (P = 0.018) were significantly related to higher response. Age did not significantly relate to overall survival (OS) or progression-free survival (PFS). First-line therapy, better PS, estrogen receptor positive status and a fewer number of metastatic sites were significantly related to improved OS and PFS. The grade >= 3 toxic effects that increased linearly with age were leucopenia (P = 0.0099), granulocytopenia (P = 0.022), anorexia (P = 0.028), bilirubin elevation (P = 0.0035) and neurotoxicity (P < 0.0001). Patients over 65 years receiving second-line therapy had the shortest time to neurotoxicity. Conclusions: Older women with breast cancer derive similar efficacy from treatment with paclitaxel as younger women. Older women are at increased risk for specific toxic effects. C1 [Lichtman, S. M.; Seidman, A. D.; Hudis, C.] Mem Sloan Kettering Canc Ctr, Dept Med, Commack, NY 11725 USA. [Hurria, A.] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA. [Hurria, A.] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA USA. [Cirrincione, C. T.] CALGB Stat Ctr, Durham, NC USA. [Winer, E.] Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. [Cohen, H. J.] Duke Univ, Ctr Study Aging & Human Dev, Durham, NC 27706 USA. [Muss, H. B.] Univ N Carolina, UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA. RP Lichtman, SM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 650 Commack Rd, Commack, NY 11725 USA. EM lichtmas@mskcc.org FU National Cancer Institute [CA31946, CA33601, CA45418, CA32291, CA77597, CA11028, CA12449, CA03927, CA77651, CA45564, CA04457, CA35421, CA35279, CA08025, CA02599, CA45808, CA21060, CA45389, CA77658, CA47545, CA11789, CA60138, CA41287, CA74811, CA47642, CA31983, CA37135]; the National Cancer Institute [CA16450, CA12046, CA77298, CA47559, CA47555, CA77406, CA26806, CA77440, CA07968] FX The research for CALGB 9342 and 9840 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Monica M. Bertagnolli) and to the CALGB Statistical Center (Daniel J. Sargent, CA33601). The following institutions participated in this study: CALGB Statistical Office, Durham, NC. Stephen George, supported by CA33601; Christiana Care Health Services, Inc CCOP, Wilmington, DE. Stephen Grubbs, supported by CA45418; Dana-Farber Cancer Institute, Boston, MA. George P. Canellos, supported by CA32291; Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, NH. Marc S. Ernstoff, supported by Georgetown University Medical Center, Washington, DC. Edward Gelmann, supported by CA77597; Long Island Jewish Medical Center, Lake Success, NY. Marc Citron, supported by CA11028; Massachusetts General Hospital, Boston, MA. Michael L. Grossbard, supported by CA12449; Medical University of South Carolina, Charleston, SC. Mark Green, supported by CA03927; Memorial Sloan-Kettering Cancer Center, New York, NY. Clifford Hudis, supported by CA77651; Missouri Baptist Medical Center, St Louis, MO. Alan P. Lyss, Mount Sinai Medical Center, Miami, FL. Rogerio Lilenbaum, supported by CA45564; Mount Sinai School of Medicine, New York, NY. Lewis R. Silverman, supported by CA04457; Nevada Cancer Research Foundation CCOP, Las Vegas, NV. John Ellerton, supported by CA35421; New Hampshire Oncology-Hematology P. A., Hooksett, NH. Douglas J. Weckstein, North Shore, Long Island Jewish Medical Center, Manhasset, NY. Daniel R. Budman, supported by CA35279; Rhode Island Hospital, Providence, RI. Louis A. Leone, supported by CA08025; Roswell Park Cancer Institute, Buffalo, NY. Ellis Levine, supported by CA02599; Southeast Cancer Control Consortium Inc CCOP, Goldsboro, NC. James N. Atkins, supported by CA45808; State University of New York Upstate Medical University, Syracuse, NY. Stephen L. Graziano, supported by CA21060; Syracuse Hematology-Oncology Assoc. CCOP, Syracuse, NY. Jeffrey Kirshner, supported by CA45389; The Ohio State University Medical Center, Columbus, OH. Clara D. Bloomfield, supported by CA77658; University of Alabama Birmingham, Birmingham, AL. Robert Diasio, supported by CA47545; University of California at San Diego, San Diego, CA. Joanne Mortimer, supported by CA11789; University of California at San Francisco, San Francisco, CA. Alan P. Venook, supported by CA60138; University of Chicago Medical Center, Chicago, IL. Gini Fleming, supported by CA41287; University of Illinois at Chicago, Chicago, IL. David Gustin, supported by CA74811; University of Iowa, Iowa City, IA. Gerald Clamon, supported by CA47642; University of Maryland Cancer Center, Baltimore, MD. David Van Echo, supported by CA31983; University of Massachusetts Medical Center, Worcester, MA. Mary Ellen Taplin, supported by CA37135; University of Minnesota, Minneapolis, MN. Bruce A. Peterson, supported by CA16450; University of Missouri/Ellis Fischel Cancer Ctr., Columbia, MO. Michael C. Perry, supported by CA12046; University of Nebraska Medical Center, Omaha, NE. Anne Kessinger, supported by CA77298; University of North Carolina at Chapel Hill, Chapel Hill, NC. Thomas C. Shea, supported by CA47559; University of Tennessee Memphis, Memphis, TN. Harvey B. Niell, supported by CA47555; Vermont Cancer Center, Burlington, VT. Hyman B. Muss, supported by CA77406; Wake Forest University School of Medicine, Winston-Salem, NC. David D. Hurd; supported by CA03927; Walter Reed Army Medical Center, Washington, DC. John C.; Byrd, supported by CA26806; Washington University, St Louis, MO. Nancy Bartlett, supported by CA77440; Weill Medical College of Cornell University, New York, NY. Michael Schuster, supported by CA07968. NR 20 TC 18 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2012 VL 23 IS 3 BP 632 EP + DI 10.1093/annonc/mdr297 PG 7 WC Oncology SC Oncology GA 898HV UT WOS:000300733300014 PM 21693770 ER PT J AU Gronchi, A Bui, BN Bonvalot, S Pilotti, S Ferrari, S Hohenberger, P Hohl, RJ Demetri, GD Le Cesne, A Lardelli, P Perez, I Nieto, A Tercero, JC Alfaro, V Tamborini, E Blay, JY AF Gronchi, A. Bui, B. N. Bonvalot, S. Pilotti, S. Ferrari, S. Hohenberger, P. Hohl, R. J. Demetri, G. D. Le Cesne, A. Lardelli, P. Perez, I. Nieto, A. Tercero, J. C. Alfaro, V. Tamborini, E. Blay, J. Y. TI Phase II clinical trial of neoadjuvant trabectedin in patients with advanced localized myxoid liposarcoma SO ANNALS OF ONCOLOGY LA English DT Article DE chemotherapy; liposarcoma; neoadjuvant; soft tissue sarcoma; surgery ID SOFT-TISSUE SARCOMA; PRIMARY EXTREMITY LIPOSARCOMA; OVARIAN-CANCER; CHEMOTHERAPY; ECTEINASCIDIN-743; ET-743; IMPACT; SCHEDULES; SURVIVAL; EFFICACY AB Background: To evaluate neoadjuvant trabectedin (1.5 mg/m(2) 24-h i.v. infusion every 3 weeks; three to six cycles) in patients with locally advanced myoxid liposarcoma (ML) previously untreated with chemotherapy or radiation. Patients and methods: Primary efficacy end point was pathological complete response (pCR) or tumoral regression rate. Objective response according to RECIST (v.1.0) was a secondary end point. Results: Three of 23 assessable patients had pCR [13%; 95% confidence interval (CI), 3% to 34%]. Furthermore, very good and moderate histological responses were observed in another 2 and 10 patients, respectively. Histological decrement in the cellular and vascular tumor component and maturation of tumor cells to lipoblasts were observed in both myoxid and myoxid/round cell variants. Seven patients had partial response according to RECIST (objective response rate of 24%; 95% CI, 10% to 44%). No disease progression was reported. Neoadjuvant trabectedin was usually well tolerated, with a safety profile similar to that described in patients with soft tissue sarcoma or other tumor types. Conclusion: Trabectedin 1.5 mg/m(2) given as a 24-h i.v. infusion every 3 weeks is a therapeutic option in the neoadjuvant setting of ML. C1 [Gronchi, A.; Pilotti, S.; Tamborini, E.] Natl Canc Inst, Dept Surg, I-20133 Milan, Italy. [Bui, B. N.] Inst Bergonie, Dept Med Oncol, Bordeaux, France. [Bonvalot, S.; Le Cesne, A.] Inst Gustave Roussy, Dept Surg, Paris, France. [Bonvalot, S.; Le Cesne, A.] Inst Gustave Roussy, Dept Med Oncol, Paris, France. [Ferrari, S.] Orthoped Inst Rizzoli, Dept Chemotherapy, Bologna, Italy. [Hohenberger, P.] Heidelberg Univ, Mannheim Univ Med Ctr, Div Surg Oncol & Thorac Surg, D-6900 Heidelberg, Germany. [Demetri, G. D.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lardelli, P.; Perez, I.; Nieto, A.; Tercero, J. C.; Alfaro, V.] PharmaMar, Dept Clin R&D, Madrid, Spain. [Blay, J. Y.] Leon Berard Canc Ctr, Dept Med Oncol, Lyon, France. RP Gronchi, A (reprint author), Natl Canc Inst, Dept Surg, Via G Venezian 1, I-20133 Milan, Italy. EM alessandro.gronchi@istitutotumori.mi.it RI Blay, Jean-Yves/N-3966-2016; Tamborini, Elena/C-3307-2017; OI Blay, Jean-Yves/0000-0001-7190-120X; Tamborini, Elena/0000-0002-3819-8687; Gronchi, Alessandro/0000-0002-4703-3534 FU PharmaMar S.A., Sociedad Unipersonal [NCT00579501]; Novartis; Pfizer; Roche; PharmaMar; Amgen; Ariad; Daiichi-Sankyo; Infinity Pharmaceuticals; Johnson Johnson; PhamaMar FX PharmaMar S.A., Sociedad Unipersonal (ClinicalTrials.gov number, NCT00579501).; BNB (GlaxoSmithKline, Imclone, Novartis, Pfizer, PharmaMar, Roche, MSD), PH (PharmaMar), GDD (Amgen, Ariad, ArQule, Champions Biotechnology, Daiichi-Sankyo, EMD-Serono, Enzon, Genentech, GlaxoSmithKline, Infinity Pharmaceuticals, Johnson & Johnson, Koltan Phamaceuticals, Millenium/Takeda, N-of-One, Novartis, Pfizer, PharmaMar, Plekkixon, Ziopharm), ALC (PharmaMar) and JYB (PhamaMar) were compensated as consultants or advisors. BNB (GlaxoSmithKline, Imclone, MSD, Novartis, Pfizer, Roche), SB (Novartis), PH (PharmaMar), GDD (Novartis, Pfizer), ALC (PharmaMar) and JYB (PhamaMar) received honoraria. BNB (Novartis, Pfizer, Roche), SB (Novartis), RJH (PharmaMar), SF (PharmaMar), GDD (Amgen, Ariad, Daiichi-Sankyo, Infinity Pharmaceuticals, Johnson & Johnson, Novartis, Pfizer, PhamaMar) and JYB (PhamaMar) received research funding. GDD (Ariad, Inifinity Pharmaceuticals, Johnson & Johnson, PharmaMar, Ziopharm) gave expert testimony. AG received remuneration from PharmaMar. PL, IP, AN, JCT and VA are employees in PharmaMar. PL (Zeltia), IP (Zeltia), AN (Zeltia) and JCT (Zeltia) are stock ownership. NR 25 TC 62 Z9 62 U1 0 U2 2 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 MAR PY 2012 VL 23 IS 3 BP 771 EP 776 DI 10.1093/annonc/mdr265 PG 6 WC Oncology SC Oncology GA 898HV UT WOS:000300733300035 PM 21642514 ER PT J AU Lenihan, D Suter, T Brammer, M Neate, C Ross, G Baselga, J AF Lenihan, D. Suter, T. Brammer, M. Neate, C. Ross, G. Baselga, J. TI Pooled analysis of cardiac safety in patients with cancer treated with pertuzumab SO ANNALS OF ONCOLOGY LA English DT Article DE cardiac; combination; HER; pertuzumab; safety ID METASTATIC BREAST-CANCER; EPIDERMAL-GROWTH-FACTOR; TRASTUZUMAB-RELATED CARDIOTOXICITY; RECEPTOR DIMERIZATION INHIBITOR; SINGLE-AGENT PERTUZUMAB; ADVANCED SOLID TUMORS; RHUMAB 2C4; PHASE-II; ADJUVANT TRASTUZUMAB; VENTRICULAR MYOCYTES AB Background: Pertuzumab, a human epidermal growth factor receptor (HER) 2 dimerization inhibitor, has demonstrated promising efficacy in combination with trastuzumab in patients with metastatic breast cancer. As HER signaling pathways are not only involved in oncogenesis, but also in myocardial homeostasis, an analysis of cardiac safety data was undertaken in a large group of patients treated with pertuzumab. Patients and methods: A complete database of patients treated with full-dose pertuzumab was used to describe the incidence of asymptomatic left ventricular systolic dysfunction (LVSD) and symptomatic heart failure (HF). Results: Information for 598 unique patients was available for the current analysis. Of the patients treated with pertuzumab alone (n = 331) or pertuzumab in combination with a non-anthracycline-containing cytotoxic (n = 175) or trastuzumab (n = 93), 23 (6.9%), 6 (3.4%), and 6 (6.5%), respectively, developed asymptomatic LVSD and 1 (0.3%), 2 (1.1%), and 1 (1.1%), respectively, displayed symptomatic HF. None of the 15 patients receiving both pertuzumab and erlotinib demonstrated LVSD. Conclusions: Patients treated with pertuzumab experienced relatively low levels of asymptomatic LVSD or symptomatic HF. There was no notable increase in cardiac side-effects when pertuzumab was given in combination with other anticancer agents. C1 [Lenihan, D.] Vanderbilt Univ, Dept Cardiovasc Med, Nashville, TN 37232 USA. [Suter, T.] Univ Hosp Bern, Dept Cardiol, CH-3010 Bern, Switzerland. [Suter, T.] Univ Bern, Bern, Switzerland. [Brammer, M.] Genentech Inc, BioOncol, US Med Affairs, San Francisco, CA 94080 USA. [Neate, C.] Roche Prod Ltd, Pharmaceut Dev, Biostat, Welwyn Garden City AL7 3AY, Herts, England. [Ross, G.] Roche Prod Ltd, Pharmaceut Dev Oncol, Welwyn Garden City AL7 3AY, Herts, England. [Baselga, J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Baselga, J.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Lenihan, D (reprint author), Vanderbilt Univ, Dept Cardiovasc Med, 1215 21st Ave,Suite 5209, Nashville, TN 37232 USA. EM daniel.lenihan@vanderbilt.edu FU F. Hoffmann-La Roche Ltd; Genentech, Inc.; Roche FX This analysis was sponsored by F. Hoffmann-La Roche Ltd and Genentech, Inc.; MB is an employee of Genentech and has a stock interest in Roche; C. Neate is an employee of Roche Products Ltd, UK; GR is an employee of Roche Products; DL has acted as a consultant to AstraZeneca; TS has received a commercial research grant from Roche, speaker bureau honoraria from sanofi-aventis and Chugai, and has acted as a consultant to GSK. NR 52 TC 41 Z9 42 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2012 VL 23 IS 3 BP 791 EP 800 DI 10.1093/annonc/mdr294 PG 10 WC Oncology SC Oncology GA 898HV UT WOS:000300733300038 PM 21665955 ER PT J AU Kumar, A Goldfarb, JW Bittner, EA AF Kumar, Asheesh Goldfarb, Jeremy W. Bittner, Edward A. TI A case of drug rash with eosinophilia and systemic symptoms (DRESS) syndrome complicating airway management SO CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article ID HYPERSENSITIVITY-SYNDROME; CARBAMAZEPINE AB Purpose Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe multi-system reaction defined by fever, rash, eosinophilia, and internal organ involvement. The condition typically occurs one to eight weeks following exposure to inciting medications. In severe cases, it can develop into multi-organ system failure and death. We present a case of DRESS syndrome with mucosal edema that led to extreme difficulties with airway management. Clinical features A 65-yr-old male treated for an esophageal perforation with broad-spectrum antibiotics developed fever, eosinophilia, and extensive rash consistent with DRESS syndrome. This condition resulted in a rapid progression to multi-organ system dysfunction, severe hemodynamic instability, and the need for high-dose vasopressors and tracheal intubation. Extensive mucous membrane involvement led to significant complications with airway management and a nearly impossible tracheal intubation, features in the disease not previously described. With the airway secure, initiation of steroids resulted in regression of the disease within 24 hr, resolution of airway edema, and uneventful tracheal extubation a few days later. Conclusion We emphasize the need for early identification of DRESS syndrome as well as the possible airway implications associated with this increasingly recognized clinical entity. C1 [Kumar, Asheesh] Uniformed Hlth Sci Univ, Dept Anesthesiol, Walter Reed Natl Mil Med Ctr Bethesda, Bethesda, MD 20889 USA. [Kumar, Asheesh; Bittner, Edward A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. [Goldfarb, Jeremy W.] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. RP Kumar, A (reprint author), Uniformed Hlth Sci Univ, Dept Anesthesiol, Walter Reed Natl Mil Med Ctr Bethesda, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM Asheesh.Kumar@med.navy.mil NR 11 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0832-610X J9 CAN J ANESTH JI Can. J. Anesth. PD MAR PY 2012 VL 59 IS 3 BP 295 EP 298 DI 10.1007/s12630-011-9644-x PG 4 WC Anesthesiology SC Anesthesiology GA 916KT UT WOS:000302103100008 PM 22271506 ER PT J AU Yang, Y Schuhle, DT Dai, GP Alford, JK Caravan, P AF Yang, Yan Schuehle, Daniel T. Dai, Guangping Alford, Jamu K. Caravan, Peter TI 1H chemical shift magnetic resonance imaging probes with high sensitivity for multiplex imaging SO CONTRAST MEDIA & MOLECULAR IMAGING LA English DT Article DE Chemical shift imaging; multiplex; gadolinium ID QUANTITATIVE TISSUE OXIMETRY; CONTRAST AGENT; SPECTROSCOPY; NANOPARTICLES; COMPLEXES; LIPOSOMES; MRI AB Proton-based chemical shift imaging probes were encapsulated inside nano-carriers to increase the sensivitity of the reporters. Co-encapsulation with a relaxation agent results in improved sensitivity and suppresses background signals. Simultaneous imaging of different chemical shift reporters allows multiplexed detection. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Yang, Yan; Schuehle, Daniel T.; Dai, Guangping; Alford, Jamu K.; Caravan, Peter] Massachusetts Gen Hosp, Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Yang, Yan] Wuhan Univ, Zhongnan Hosp, Wuhan 430072, Hubei Province, Peoples R China. RP Caravan, P (reprint author), Massachusetts Gen Hosp, Ctr Biomed Imaging, Harvard Med Sch 149,13th St,Suite 2301, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU German Academic Exchange Service; National Institute of Biomedical Imaging and Bioengineering [R01EB009062]; National Center for Research Resources [P41RR14075, S10RR025563] FX This work was partially supported by a fellowship within the postdoc-program of the German Academic Exchange Service, by grant R01EB009062 from the National Institute of Biomedical Imaging and Bioengineering, and by grants P41RR14075 and S10RR025563 from the National Center for Research Resources. NR 20 TC 3 Z9 3 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1555-4309 J9 CONTRAST MEDIA MOL I JI Contrast Media Mol. Imaging PD MAR PY 2012 VL 7 IS 2 BP 276 EP 279 DI 10.1002/cmmi.490 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 911JU UT WOS:000301713900020 PM 22434641 ER PT J AU Razansky, D Deliolanis, NC Vinegoni, C Ntziachristos, V AF Razansky, Daniel Deliolanis, Nikolaos C. Vinegoni, Claudio Ntziachristos, Vasilis TI Deep Tissue Optical and Optoacoustic Molecular Imaging Technologies for Pre-Clinical Research and Drug Discovery SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE Optical molecular imaging; drug discovery; optoacoustic tomography; small animals; contrast agents; in-vivo imaging ID RESOLUTION PHOTOACOUSTIC MICROSCOPY; LAPLACIAN-TYPE REGULARIZATION; NEAR-INFRARED TOMOGRAPHY; IN-VIVO; PROJECTION TOMOGRAPHY; BIOLUMINESCENCE TOMOGRAPHY; FLUORESCENCE TOMOGRAPHY; SMALL ANIMALS; CONTRAST AGENTS; GOLD NANORODS AB For centuries, biological discoveries were based on optical imaging, in particular microscopy but also several chromophoric assays and photographic approaches. With the recent emergence of methods appropriate for bio-marker in vivo staining, such as bioluminescence, fluorescent molecular probes and proteins, as well as nanoparticle-based targeted agents, significant attention has been shifted toward in vivo interrogations of different dynamic biological processes at the molecular level. This progress has been largely supported by the development of advanced tomographic imaging technologies suitable for obtaining volumetric visualization of bio-marker distributions in small animals at a whole-body or whole-organ scale, an imaging frontier that is not accessible by the existing tissue-sectioning microscopic techniques due to intensive light scattering beyond the depth of a few hundred microns. Major examples of such recently developed optical imaging modalities are reviewed here, including bioluminescence tomography (BLT), fluorescence molecular tomography (FMT), and optical projection tomography (OPT). The pharmaceutical imaging community has quickly appropriated itself of these novel forms of optical imaging, since they come with very compelling advantages, such as quantitative three-dimensional capabilities, direct correlation to the biological cultures, easiness and cost-effectiveness of use, and the use of safe non-ionizing radiation. Some multi-modality approaches, combining light with other imaging modalities such as X-Ray CT or MRI, giving the ability to acquire both an optical contrast reconstruction along with a hi-fidelity anatomical images, are also reviewed. A separate section is devoted to the hybrid imaging techniques based on the optoacoustic phenomenon, such as multispectral optoacoustic tomography (MSOT), which are poised to leverage the traditional contrast and specificity advantages of optical spectrum by delivering an ever powerful set of capabilities, including real-time operation and high spatial resolution, not affected by the scattering nature of biological tissues. C1 [Razansky, Daniel; Deliolanis, Nikolaos C.; Ntziachristos, Vasilis] Tech Univ Munich, IBMI, D-85764 Neuherberg, Germany. [Razansky, Daniel; Deliolanis, Nikolaos C.; Ntziachristos, Vasilis] Helmholtz Ctr Munich, D-85764 Neuherberg, Germany. [Vinegoni, Claudio] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Razansky, D (reprint author), Tech Univ Munich, IBMI, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany. EM dr@tum.de OI Deliolanis, Nikolaos/0000-0002-6392-3035 NR 95 TC 33 Z9 34 U1 1 U2 50 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD MAR PY 2012 VL 13 IS 4 BP 504 EP 522 PG 19 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 916PS UT WOS:000302116300003 PM 22216767 ER PT J AU Bennett, KO Billings, CJ Molis, MR Leek, MR AF Bennett, Keri O'Connell Billings, Curtis J. Molis, Michelle R. Leek, Marjorie R. TI Neural Encoding and Perception of Speech Signals in Informational Masking SO EAR AND HEARING LA English DT Article ID EVENT-RELATED POTENTIALS; SOUNDS VERTICAL-BAR; PASS NOISE MASKING; BROAD-BAND NOISE; NORMAL-HEARING; RECOGNITION; FREQUENCY; LISTENERS; WAVE; N1 AB Objective: To investigate the contributions of energetic and informational masking to neural encoding and perception in noise, using oddball discrimination and sentence recognition tasks. Design: P3 auditory evoked potential, behavioral discrimination, and sentence recognition data were recorded in response to speech and tonal signals presented to nine normal-hearing adults. Stimuli were presented at a signal to noise ratio of -3 dB in four background conditions: quiet, continuous noise, intermittent noise, and four-talker babble. Results: Responses to tonal signals were not significantly different for the three maskers. However, responses to speech signals in the four-talker babble resulted in longer P3 latencies, smaller P3 amplitudes, poorer discrimination accuracy, and longer reaction times than in any of the other conditions. Results also demonstrate significant correlations between physiological and behavioral data. As latency of the P3 increased, reaction times also increased and sentence recognition scores decreased. Conclusion: The data confirm a differential effect of masker type on the P3 and behavioral responses and present evidence of interference by an informational masker to speech understanding at the level of the cortex. Results also validate the use of the P3 as a useful measure to demonstrate physiological correlates of informational masking. C1 [Bennett, Keri O'Connell; Billings, Curtis J.; Molis, Michelle R.; Leek, Marjorie R.] Portland VA Med Ctr, NCRAR, Portland, OR 97239 USA. [Bennett, Keri O'Connell; Billings, Curtis J.; Molis, Michelle R.; Leek, Marjorie R.] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. RP Bennett, KO (reprint author), Portland VA Med Ctr, NCRAR, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM keri.oconnell2@va.gov FU National Institute on Deafness and Other Communication Disorders [R01 DC 00626]; Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service [C6116W, C6971M] FX This research was supported by a grant R01 DC 00626 from the National Institute on Deafness and Other Communication Disorders. Support was also provided by the Department of Veterans Affairs, Veterans Health Administration, Rehabilitation Research and Development Service [Career Development grants C6116W (to M.R.M.) and C6971M (to C.J.B.), and Senior Research Career Scientist award (to M.R.L.)]. The work was supported with resources and the use of facilities at the Portland VA Medical Center. NR 28 TC 12 Z9 12 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD MAR-APR PY 2012 VL 33 IS 2 BP 243 EP 250 DI 10.1097/AUD.0b013e31823173fd PG 8 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 899YM UT WOS:000300852600009 PM 22367094 ER PT J AU Shafi, MM Westover, MB Fox, MD Pascual-Leone, A AF Shafi, Mouhsin M. Westover, M. Brandon Fox, Michael D. Pascual-Leone, Alvaro TI Exploration and modulation of brain network interactions with noninvasive brain stimulation in combination with neuroimaging SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE EEG; fMRI; functional connectivity; human; transcranial direct current stimulation; transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; DORSOLATERAL PREFRONTAL CORTEX; STATE FUNCTIONAL CONNECTIVITY; GRAPH-THEORETICAL ANALYSIS; SMALL-WORLD NETWORKS; CORTICAL EFFECTIVE CONNECTIVITY; MOOD-REGULATING CIRCUIT; HUMAN DORSAL PREMOTOR; DEFAULT-MODE NETWORK AB Much recent work in systems neuroscience has focused on how dynamic interactions between different cortical regions underlie complex brain functions such as motor coordination, language and emotional regulation. Various studies using neuroimaging and neurophysiologic techniques have suggested that in many neuropsychiatric disorders, these dynamic brain networks are dysregulated. Here we review the utility of combined noninvasive brain stimulation and neuroimaging approaches towards greater understanding of dynamic brain networks in health and disease. Brain stimulation techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation, use electromagnetic principles to alter brain activity noninvasively, and induce focal but also network effects beyond the stimulation site. When combined with brain imaging techniques such as functional magnetic resonance imaging, positron emission tomography and electroencephalography, these brain stimulation techniques enable a causal assessment of the interaction between different network components, and their respective functional roles. The same techniques can also be applied to explore hypotheses regarding the changes in functional connectivity that occur during task performance and in various disease states such as stroke, depression and schizophrenia. Finally, in diseases characterized by pathologic alterations in either the excitability within a single region or in the activity of distributed networks, such techniques provide a potential mechanism to alter cortical network function and architectures in a beneficial manner. C1 [Shafi, Mouhsin M.; Westover, M. Brandon; Fox, Michael D.; Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Div Cognit Neurol, Dept Neurol, Boston, MA 02215 USA. [Shafi, Mouhsin M.; Westover, M. Brandon; Fox, Michael D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Shafi, Mouhsin M.; Westover, M. Brandon; Fox, Michael D.; Pascual-Leone, Alvaro] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Pascual-Leone, Alvaro] Univ Autonoma Barcelona, Inst Univ Neurorehabil Guttmann, Badalona, Spain. RP Pascual-Leone, A (reprint author), Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Div Cognit Neurol, Dept Neurol, 330 Brookline Ave, Boston, MA 02215 USA. EM apleone@bidmc.harvard.edu FU National Center for Research Resources: Harvard Clinical and Translational Science Center [UL1 RR025758]; Center for Integration of Medicine and Innovative Technology (CIMIT); Sidney R. Baer, Jr. Foundation; Nexstim; NIH [R01-NS062092, R25-NS065743] FX Work on this study was supported by grants from the National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758), Center for Integration of Medicine and Innovative Technology (CIMIT), the Sidney R. Baer, Jr. Foundation, and Nexstim to A.P.L. M.S. was supported by funds from the National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758), and the Center for Integration of Medicine and Innovative Technology (CIMIT). M. B. W. was supported by NIH Grant R01-NS062092. M.D.F. was supported by NIH Grant R25-NS065743. A.P.L. serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Allied Mind, Neosync and Novavision, and is an inventor on patents and patent applications related to noninvasive brain stimulation and the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging. M.M.S., M.B.W. and M.D.F. declare no conflict of interest. NR 201 TC 43 Z9 44 U1 1 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2012 VL 35 IS 6 BP 805 EP 825 DI 10.1111/j.1460-9568.2012.08035.x PG 21 WC Neurosciences SC Neurosciences & Neurology GA 910PR UT WOS:000301652300001 PM 22429242 ER PT J AU Connolly, KR Thase, ME AF Connolly, Kevin Ryan Thase, Michael E. TI Emerging drugs for major depressive disorder SO EXPERT OPINION ON EMERGING DRUGS LA English DT Review DE bipolar disorder; major depressive disorder; medication; treatment ID SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED-TRIAL; TREATMENT-RESISTANT DEPRESSION; RANDOMIZED CONTROLLED-TRIALS; EXTENDED-RELEASE QUETIAPINE; GLUTAMATE-RECEPTOR AGONISTS; BDNF MESSENGER-RNA; DOUBLE-BLIND; OLANZAPINE/FLUOXETINE COMBINATION; ADJUNCTIVE THERAPY AB Introduction: Major depressive disorder (MDD) remains a major public health concern, and one that continues to suffer an incompletely-met need for effective and acceptable treatments. The development of antidepressants, to date, has focused primarily on increasing monoamine neurotransmission with increasing efficacy while minimizing adverse effects. Medications currently recommended as 'first-line' are far more tolerable than the older medications they replaced, but as many as 70% of patients continue to suffer significant depressive symptoms after treatment with one of these agents, and as many as 50% will discontinue a trial due to issues with acceptability. This review will summarize antidepressants that have recently entered the market as well as those still in development to help characterize the current state of antidepressant development. Areas covered: Currently available first-line antidepressants are reviewed with respect to efficacy and tolerability, and their weaknesses are discussed as targets for future development. The background, clinical trial data and potential significance of the three most recently introduced antidepressants (trazodone-ER, desvenlafaxine and vilazodone) and the most recently approved augmentation agents (aripiprazole and quetiapine) are discussed. Following a review of the current market, all medications currently in Phase II or later clinical trials are listed and discussed, based on a thorough review of the US National Institutes of Health clinicaltrials.gov index for trials using medications to treat MDD and a search of the Informa Pharmaprojects database for medications currently being developed for a depression indication. Compounds thus identified were then used as search terms in a PubMed search of each medication. Based on pharmacologic properties, medications in development were grouped into those acting on: i) monoamine neurotransmission; ii) cholinergic neurotransmission; iii) glutamatergic neurotransmission; iv) opioid receptors; v) sigma receptors; vi) neurokinin receptors; vii) corticotrophin-releasing factor receptors and viii) other mechanisms. In the discussion of each, a brief review of the pharmacology and physiology of the related system is provided. Potential issues for the future of antidepressant development and an expert opinion are discussed. Expert opinion: The past decade has not yielded a large number of new antidepressants and, with the possible exception of agomelatine, none of the newer medications that have been introduced have decisively addressed the several unmet needs in this area of therapeutics. Among the various novel strategies that are being evaluated, results of several small studies of ketamine suggest that drugs that modulate glutamatergic neurotransmission may hold the greatest promise for exerting rapid and large antidepressant effects in patients who have not responded to SSRIs or SNRIs. C1 [Connolly, Kevin Ryan; Thase, Michael E.] Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. [Connolly, Kevin Ryan] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Connolly, KR (reprint author), Univ Penn, Perelman Sch Med, Philadelphia Vet Affairs Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM kevin.connolly2@va.gov FU Agency for Healthcare Research and Quality; Eli Lilly Co.; Forest Pharmaceuticals; GlaxoSmithKline; NIMH; Otsuka Pharmaceuticals; Pfizer Pharmaceuticals; Roche, Inc. FX KR Connolly states no conflict of interest and has received no payment in preparation of this manuscript. ME Thase has earned income as a consultant to Aldolor, Alkermes, AstraZeneca, Bristol-Myers Squibb, Dey Pharmaceuticals, Eli Lilly & Co., Forest Laboratories, Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante, Inc., Merck (Organon; Schering-Plough), Neuronetics, Inc., Novartis, Otsuka, Ortho-McNeil (Johnson & Johnson), PamLab, Pfizer (Wyeth), PharmaNeuroboost, Rexahn, Roche, Inc., Shire US, Inc., Supernus, Takeda and Transcept. He has also received grants from the Agency for Healthcare Research and Quality, Eli Lilly & Co., Forest Pharmaceuticals, GlaxoSmithKline, NIMH, Otsuka Pharmaceuticals, Pfizer Pharmaceuticals and Roche, Inc. NR 107 TC 35 Z9 36 U1 4 U2 36 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1472-8214 EI 1744-7623 J9 EXPERT OPIN EMERG DR JI Expert Opin Emerg. Drugs PD MAR PY 2012 VL 17 IS 1 BP 105 EP 126 DI 10.1517/14728214.2012.660146 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 915LA UT WOS:000302025800010 PM 22339643 ER PT J AU Pidala, J Vogelsang, G Martin, P Chai, XY Storer, B Pavletic, S Weisdorf, DJ Jagasia, M Cutler, C Palmer, J Jacobsohn, D Arai, S Lee, SJ AF Pidala, Joseph Vogelsang, Georgia Martin, Paul Chai, Xiaoyu Storer, Barry Pavletic, Steven Weisdorf, Daniel J. Jagasia, Madan Cutler, Corey Palmer, Jeanne Jacobsohn, David Arai, Sally Lee, Stephanie J. TI Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: a Chronic Graft-versus-Host Disease Consortium study SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE overlap subtype; graft-versus-host disease; GVHD; prognosis ID QUALITY-OF-LIFE; HEMATOPOIETIC-CELL TRANSPLANTATION; CONSENSUS DEVELOPMENT PROJECT; BONE-MARROW-TRANSPLANTATION; WORKING GROUP-REPORT; CLINICAL-TRIALS; CRITERIA; SEVERITY; SCALE; VALIDATION AB Background The National Institutes of Health Consensus Conference proposed the term "overlap" graft-versus-host disease to describe the situation when both acute and chronic graft-versus-host disease are present. Design and Methods We examined whether the overlap subtype of graft-versus-host disease was associated with a different prognosis, functional limitations, or patient-reported outcomes compared to "classic" chronic graft-versus-host disease without any acute features. Results Prospective data were collected from 427 patients from nine centers. Patients were classified as having overlap (n=352) or classic chronic (n=75) graft-versus-host disease based on reported organ involvement. Overlap cases had a significantly shorter median time from transplantation to cohort enrollment (P=0.01), were more likely to be incident cases (P < 0.001), and had a lower platelet count at onset of the graft-versus-host disease (P < 0.001). Patients with overlap graft-versus-host disease had significantly greater functional impairment measured by a 2-minute walk test, higher symptom burden and lower Human Activity Profile scores. Quality of life was similar, except patients with overlap graft-versus-host disease had worse social functioning, assessed by the Short Form-36. Multivariable analysis utilizing time-varying covariates demonstrated that the overlap subtype of graft-versus-host disease was associated with worse overall survival (HR 2.1, 95% CI 1.1-4.7; P=0.03) and higher non-relapse mortality (HR 2.8, 95% CI 1.2-8.3; P=0.02) than classic chronic graft-versus-host disease. Conclusions These findings suggest that the presence of acute features in patients with chronic graft-versus-host disease is a marker of adverse prognosis, greater functional impairment, and higher symptom burden. C1 [Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Vogelsang, Georgia] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Martin, Paul; Chai, Xiaoyu; Storer, Barry; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Pavletic, Steven] NCI, Bethesda, MD 20892 USA. [Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA. [Jagasia, Madan] Vanderbilt Univ, Nashville, TN USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Palmer, Jeanne] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Jacobsohn, David] Childrens Mem Hosp, Chicago, IL 60614 USA. [Arai, Sally] Stanford Univ, Stanford, CA 94305 USA. RP Pidala, J (reprint author), Blood & Marrow Transplantat Moffitt Canc Ctr, 12902 Magnolia Dr,FOB 3308, Tampa, FL 33612 USA. EM joseph.pidala@moffitt.org FU NCI NIH HHS [P30 CA015704, P30 CA076292, U54 CA163438] NR 33 TC 24 Z9 24 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD MAR PY 2012 VL 97 IS 3 BP 451 EP 458 DI 10.3324/haematol.2011.055186 PG 8 WC Hematology SC Hematology GA 914TP UT WOS:000301975700024 PM 22058206 ER PT J AU Pointer, MA Daumerie, G Bridges, L Yancey, S Howard, K Davis, W Huang, P Loscalzo, J AF Pointer, Mildred A. Daumerie, Geraldine Bridges, LaKessha Yancey, Sadiqa Howard, Kelly Davis, Wendell Huang, Paul Loscalzo, Joseph TI Physiological stress increases renal injury in eNOS-knockout mice SO HYPERTENSION RESEARCH LA English DT Article DE kidney injury; salt; stress ID NITRIC-OXIDE SYNTHASE; IMPROVES ENDOTHELIAL FUNCTION; AFRICAN-AMERICANS; BLOOD-PRESSURE; CARDIAC-HYPERTROPHY; SALT INTAKE; PSYCHOLOGICAL-FACTORS; CARDIOVASCULAR RISK; KIDNEY-DISEASE; EXERCISE AB African Americans have a fourfold greater likelihood of developing end-stage renal disease (ESRD) compared with Caucasians. It has been proposed that the increased prevalence may be explained by non-traditional factors such as environmental stress and psychosocial factors. In this study, we used infrequent running to exhaustion as a physiological stressor to mimic real life experiences, such walking up stairs when an elevator is malfunctioning or running to catch a bus, to study its effect on renal injury in a hypertensive mouse model (endothelial nitric oxide synthase-deficient mice; eNOS(-/-)). This model has previously been shown to have renal injury comparable to that observed in African Americans. The effect of physiological stress on renal injury was examined in the setting of low (0.12%), control (0.45%) and high (8%) dietary salt. Following bouts of physiological stress, eNOS(-/-) mice had significantly greater interstitial inflammation compared with unstressed eNOS(-/-) mice (two-way analysis of variance (2-ANOVA), Holm-Sidak; P<0.01). Interestingly, eNOS(-/-) mice on a high-salt diet had greater interstitial inflammation compared with similarly stressed eNOS(-/-) mice on a low-or control-salt diet (2-ANOVA, Holm-Sidak; P<0.03). These effects of stress were independent of systolic blood pressure (141+/-7, 143+/-4, and 158+/-8 vs. 141+/-4, 138+/-5, 150+/-4mmHg; end of study vs. baseline, respectively). There was no significant effect of stress or dietary salt on renal injury in control wild-type mice (eNOS(+/+)). These data demonstrate that physiological stress exacerbates the renal injury associated with hypertension and that high-salt compounds this effect of stress. These results provide support for the idea that psychosocial and environmental factors contribute to the increased prevalence of ESRD in hypertensive African Americans. Hypertension Research (2012) 35, 318-324; doi:10.1038/hr.2011.185; published online 15 December 2011 C1 [Pointer, Mildred A.; Bridges, LaKessha; Yancey, Sadiqa; Howard, Kelly] N Carolina Cent Univ, Dept Biol, Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA. [Daumerie, Geraldine] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Daumerie, Geraldine] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Davis, Wendell] Biogen Idec Inc, Dept Comparat Pathol, Cambridge, MA USA. [Huang, Paul] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Loscalzo, Joseph] Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. RP Pointer, MA (reprint author), N Carolina Cent Univ, Dept Biol, Julius L Chambers Biomed Biotechnol Res Inst, Durham, NC 27707 USA. EM mpointer@nccu.edu FU NCMHD [000175]; NHLBI [UH1 HL59868, R01 HL64761, R25 HL59868]; NIGMS [2 S06 GM008049] FX This work was supported in part by NCMHD 000175, NHLBI UH1 HL59868, R01 HL64761, R25 HL59868 and NIGMS 2 S06 GM008049. NR 55 TC 2 Z9 2 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0916-9636 J9 HYPERTENS RES JI Hypertens. Res. PD MAR PY 2012 VL 35 IS 3 BP 318 EP 324 DI 10.1038/hr.2011.185 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 904IP UT WOS:000301188600013 PM 22170389 ER PT J AU Hamrahi, VF Goverman, J Jung, W Wu, JC Fischman, AJ Tompkins, RG Yu, YY Fagan, SP Carter, EA AF Hamrahi, Victoria F. Goverman, Jeremy Jung, Walter Wu, Joseph C. Fischman, Alan J. Tompkins, Ronald G. Yu, Yong Y. Fagan, Shawn P. Carter, Edward A. TI In Vivo Molecular Imaging of Murine Embryonic Stem Cells Delivered to a Burn Wound Surface via Integra (R) Scaffolding SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID CULTURED SKIN SUBSTITUTES; ARTIFICIAL SKIN; REGENERATION; REPAIR AB It has been demonstrated that restoration of function to compromised tissue can be accomplished by transplantation of bone marrow stem cells and/or embryonic stem cells (ESCs). One limitation to this approach has been the lack of noninvasive techniques to longitudinally monitor stem cell attachment and proliferation. Recently, murine ESC lines that express green fluorescent protein (GFP), luciferase (LV), and herpes simplex thymidine kinase (HVTK) were developed for detection of actively growing cells in vivo by imaging. In this study, the authors investigated the use of these ESC lines in a burned mouse model using Integra (R) as a delivery scaffolding/matrix. Two different cell lines were used: one expressing GFP and LV and the other expressing GFP, LV, and HVTK. Burn wounds were produced by application of a brass block (2 x 2 cm kept in boiling water before application) to the dorsal surface of SV129 mice for 10 seconds. Twenty-four hours after injury, Integra (R) with adherent stem cells was engrafted onto a burn wound immediately after excision of eschar. The stem cells were monitored in vivo by measuring bioluminescence with a charge-coupled device camera and immunocytochemistry of excised tissue. Bioluminescence progressively increased in intensity over the time course of the study, and GFP-positive cells growing into the Integra (R) were detected. These studies demonstrate the feasibility of using Integra (R) as a scaffolding, or matrix, for the delivery of stem cells to burn wounds as well as the utility of bioluminescence for monitoring in vivo cellular tracking of stably transfected ESC cells. (J Burn Care Res 2012;33:e49-e54) C1 [Hamrahi, Victoria F.; Carter, Edward A.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Goverman, Jeremy; Jung, Walter; Tompkins, Ronald G.; Yu, Yong Y.; Fagan, Shawn P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Goverman, Jeremy; Jung, Walter; Fischman, Alan J.; Tompkins, Ronald G.; Yu, Yong Y.; Fagan, Shawn P.; Carter, Edward A.] Shriners Hosp Children, Boston, MA USA. [Goverman, Jeremy; Jung, Walter; Fischman, Alan J.; Tompkins, Ronald G.; Yu, Yong Y.; Fagan, Shawn P.; Carter, Edward A.] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Joseph C.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. RP Carter, EA (reprint author), Massachusetts Gen Hosp, Dept Pediat, 51 Blossom St, Boston, MA 02114 USA. FU National Institutes of Health [2P50 GM21700-27A]; Shriners Hospitals for Children FX Supported in part by grants from the National Institutes of Health (2P50 GM21700-27A) and Shriners Hospitals for Children. NR 16 TC 6 Z9 6 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAR-APR PY 2012 VL 33 IS 2 BP E49 EP E54 DI 10.1097/BCR.0b013e3182331d1c PG 6 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 914TU UT WOS:000301976300005 PM 22540138 ER PT J AU Spencer, TJ Bonab, AA Dougherty, DD Mirto, T Martin, J Clarke, A Fischman, AJ AF Spencer, Thomas J. Bonab, Ali A. Dougherty, Darin D. Mirto, Tara Martin, Jessica Clarke, Allison Fischman, Alan J. TI Understanding the Central Pharmacokinetics of Spheroidal Oral Drug Absorption System (SODAS) Dexmethylphenidate: A Positron Emission Tomography Study of Dopamine Transporter Receptor Occupancy Measured With C-11 Altropane SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; EXTENDED-RELEASE DEXMETHYLPHENIDATE; D-THREO-METHYLPHENIDATE; DOUBLE-BLIND; D,L-THREO-METHYLPHENIDATE HYDROCHLORIDE; LABORATORY CLASSROOM; CHILDREN; EFFICACY; PLACEBO; FORMULATIONS AB Objective: Pediatric studies of the long-acting formulation (spheroidal oral drug absorption system [SODAS]) of the isomer dexmethylphenidate have shown a dose-dependent efficacy through 12 hours. However, there are no studies of central nervous system (CNS) dopamine transporter occupancies. Method: Eighteen healthy volunteers underwent positron emission tomography (PET) imaging with C-11 altropane before and after administration of oral doses of SODAS dexmethylphenidate. Each group of 6 subjects received 1 of 3 doses (20 mg, 30 mg, 40 mg) before PET imaging at 1, 8, 10, 12 (20 mg and 30 mg), or 1, 8, 10, and 14 (40 mg) hours after dosing. Transporter occupancy was calculated by standard methods. The study was conducted from January 2007 through December 2007. Results: For all doses, plasma dexmethylphenidate levels and CNS dopamine transporter occupancies were greatest at 8 hours and decreased over time at 10, 12, and 14 hours. Plasma dexmethylphenidate levels were correlated to dose (P < .003). Mean plasma levels were 6 ng/mL to at least 8 hours with 20 mg (5.7 ng/mL), 10 hours with 30 mg, and 12 hours (extrapolated) with 40 mg. Dopamine transporter occupancies in the right caudate were 47% at 8 hours with 20 mg, 42% at hour 10 with 30 mg, and 46% (extrapolated) at hour 12 with 40 mg. Dopamine transporter occupancy was significantly correlated with plasma concentration of dexmethylphenidate (P < .001). Conclusions: These results confirm the study hypothesis that central dopamine transporter occupancy parallels peripheral pharmacokinetic findings in orally administered long-acting dexmethylphenidate in later hours after administration. Trial Registration: ClinicalTrials.gov identifier: NCT00593138 J Clin Psychiatry 2012;73(3):346-352 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Spencer, Thomas J.; Mirto, Tara; Martin, Jessica; Clarke, Allison] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Spencer, Thomas J.; Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Spencer, Thomas J.; Bonab, Ali A.; Dougherty, Darin D.; Fischman, Alan J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bonab, Ali A.] Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. [Bonab, Ali A.; Fischman, Alan J.] Shriners Hosp Children, Boston, MA USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit YAW6A, Fruit St, Boston, MA 02114 USA. EM tspencer@partners.org FU Eli Lilly; GlaxoSmithKline; Janssen; McNeil; Novartis; Cephalon; Pfizer; National Institute of Mental Health (NIMH); National Alliance for Research on Schizophrenia and Depression; Tourette Syndrome Association; Obsessive Compulsive Foundation; Wyeth; Jazz; Bristol-Myers Squibb; Brand Ideas; Reed Elsevier; Medtronic; Cyberonics; Northstar; Shire FX Dr Spencer has received research support from, has been a speaker for, or has been on a speaker bureau or advisory board of Shire, Eli Lilly, GlaxoSmithKline, Janssen, McNeil, Novartis, Cephalon, Pfizer, and the National Institute of Mental Health (NIMH). Dr Dougherty has received research funding support from NIMH, National Alliance for Research on Schizophrenia and Depression, Tourette Syndrome Association, and Obsessive Compulsive Foundation; has received honoraria, consultation fees and/or royalties from Wyeth, Jazz, Bristol-Myers Squibb, Brand Ideas, and Reed Elsevier; and has participated in research funded by Medtronic, Cyberonics, Eli Lilly, McNeil, and Northstar. Drs Bonab and Fischman and Mss Mirto, Martin, and Clarke report no financial or other interests related to the subject of the article. NR 28 TC 2 Z9 2 U1 4 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2012 VL 73 IS 3 BP 346 EP 352 DI 10.4088/JCP.10m06393 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 916OV UT WOS:000302114000010 PM 22154896 ER PT J AU Mischoulon, D Witte, J Levy, M Papakostas, GI Pet, LR Hsieh, WH Pencina, MJ Ward, S Pollack, MH Fava, M AF Mischoulon, David Witte, Janet Levy, Michael Papakostas, George I. Pet, L. Russell Hsieh, Wen-hua Pencina, Michael J. Ward, Sean Pollack, Mark H. Fava, Maurizio TI Efficacy of Dose Increase Among Nonresponders to Low-Dose Aripiprazole Augmentation in Patients With Inadequate Response to Antidepressant Treatment: A Randomized, Double-Blind, Placebo-Controlled, Efficacy Trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; ADJUNCTIVE THERAPY; QUESTIONNAIRE; MULTICENTER; SAFETY; SCALE AB Objective: To examine the efficacy of a dose increase of aripiprazole to 5 mg/d in subjects with major depressive disorder (MDD) who did not respond to 4 weeks of treatment with aripiprazole 2 mg/d in a randomized, double-blind, placebo-controlled, parent study. Method: 221 Subjects with Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition-diagnosed DSM-IV-TR MDD (mean +/- SD age, 45 +/- 11 years; 64% women) with inadequate antidepressant response were recruited from September 2008-July 2009 and randomized to 60 days of double-blind augmentation with either aripiprazole or placebo in two 30-day phases. The study was performed across 8 academic hospital sites and 14 nonacademic (private clinic) sites throughout the United States. Randomization in a 2:3:3 ratio per sequential parallel comparison design was drug/drug (aripiprazole 2 mg/d in phase 1 and 5 mg/d in phase 2), placebo/placebo (placebo in both phases), and placebo/drug (placebo in phase 1 and aripiprazole 2 mg/d in phase 2). In phase 2, we examined efficacy of an aripiprazole dose increase to 5 mg/d in nonresponders to 2 mg/d by assessing response rates 50% reduction in Montgomery-Asberg Depression Rating Scale [MADRS] score [primary outcome measure]) and score changes in MADRS, Quick Inventory of Depressive Symptomatology-Self-Report, 9-item Patient Health Questionnaire (PHQ-9), the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, and patient-rated versions of the CGI-I and CGI-S scales. Results: Response rate for aripiprazole 2 mg/d in phase 1 was 18.5% (n/n =10/54). Among 39 nonresponders who increased their dose to 5 mg/d, response rate was 12.8% (95% CI, 4.30%-27.43%), with significant overall mean SD reductions in MADRS scores (-9.46 +/- 7.83 [95% CI, -12.00 to -6.92]; P < .0001), Symptoms Questionnaire Distress scores (19.51 +/- 17.73 [95% CI, 13.60 to 25.43]; P < .0001), PHQ-9 scores (-7.92 +/- 5.92 [95% CI, -9.89 to -5.94]; P < .0001), and CGI-S scores (-0.86 +/- 0.86 [95% CI, -1.15 to -0.58]; P < .0001). Differences in efficacy between drug and placebo groups were nonsignificant, however. Aripiprazole and placebo were well tolerated. Conclusions: Augmentation with aripiprazole 5 mg/d may provide only a modest additional benefit in patients who do not benefit from lower doses. Trial Registration: clinicaltrials.gov Identifier: NCT00683852 J Clin Psychiatry 2012;73(3):353-357 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Mischoulon, David; Witte, Janet; Papakostas, George I.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Mischoulon, David; Witte, Janet; Levy, Michael; Papakostas, George I.; Pet, L. Russell; Hsieh, Wen-hua; Ward, Sean; Pollack, Mark H.; Fava, Maurizio] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Hsieh, Wen-hua; Pencina, Michael J.] Harvard Clin Res Inst, Boston, MA USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM dmischoulon@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU Laxdale (Amarin); Nordic Naturals; Ganeden; SwissMedica; Independent Medical Education (IME); MGH Psychiatry Academy; Forest Laboratories; Bristol-Myers Squibb; Forest; National Institute of Mental Health (NIMH); Pamlab; Pfizer; Ridge Diagnostics; GlaxoSmithKline; Eli Lilly; National Center for Complementary and Alternative Medicine (NCCAM); National Institute on Drug Abuse (NIDA); NIMH; Sepracor; AstraZeneca; Abbott; Alkermes; Aspect Medical Systems; BioResearch; BrainCells; Cephalon; Clinical Trial Solutions; EnVivo; Johnson Johnson; Lichtwer Pharma GmbH; Lorex; National Alliance for Research on Schizophrenia and Depression; NCCAM; NIDA; Novartis; Organon; Pharmavite; Roche; Sanofi-Aventis; Shire; Solvay; Synthelabo; Wyeth-Ayerst Laboratories FX Dr Mischoulon has received research support from Laxdale (Amarin), Nordic Naturals, Ganeden, and SwissMedica; has served as a consultant to Bristol-Myers-Squibb; has received speaking honoraria from Pamlab, Virbac, and Nordic Naturals; has received writing honoraria from Pamlab; has received royalties from Back Bay Scientific for PMS Escape and from Lippincott Williams & Wilkins for textbook Natural Medications for Psychiatric Disorders: Considering the Alternatives (David Mischoulon, MD, PhD; and Jerrold E Rosenbaum, MD; eds); has received honoraria from Reed Medical Education (a company working as a logistics collaborator for the Massachusetts General Hospital [MGM Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were supported through Independent Medical Education (IME) grants from pharmaceutical companies co-supporting programs along with participant tuition. Commercial entities currently supporting the MGH Psychiatry Academy are listed on the Academy's Website www.mghcme. org. Dr Witte is an employee of Massachusetts General Hospital, has received research support from Forest Laboratories, and has received honoraria from the American Psychiatric Association and Eli Lilly. Dr Papakostas has served as a consultant to Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Evotec AG, Inflabloc, Jazz, Otsuka, Pamlab, Pfizer, Pierre Fabre Laboratories, Shire, and Wyeth; has received honoraria from Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Evotec AG, GlaxoSmithKline, Inflabloc, Jazz, Lundbeck, Otsuka, Pamlab, Pfizer, Pierre Fabre Laboratories, Shire, Titan, and Wyeth; has received research support from Bristol-Myers Squibb, Forest, the National Institute of Mental Health (NIMH), Pamlab, Pfizer, and Ridge Diagnostics (formerly known as Precision Human Biolaboratories); and has served on the speaker's bureau for Bristol-Myers Squibb and Pfizer. Dr Pollack has served on advisory boards and consulted for BrainCells, Eli Lilly, Johnson & Johnson, Medavante, Labopharm, Mindsite, Sepracor, Targia Pharmaceuticals, and Pfizer; has received research grants from Bristol-Myers Squibb, Forest, GlaxoSmithKline, Eli Lilly, National Center for Complementary and Alternative Medicine (NCCAM), National Institute on Drug Abuse (NIDA), NIMH, and Sepracor; has received continuing medical education activity support from AstraZeneca, Sepracor, and Pfizer; has equity in Medavante, Mensante, Mindsite, and Targia Pharmaceuticals; and has received royalties for the Structured Interview Guide for the Hamilton Anxiety Scale, and SAFER interviews.; Dr Fava has received research support from Abbott, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trial Solutions, Eli Lilly, EnVivo, Forest, Ganeden, GlaxoSmithKline, Johnson & Johnson, Lichtwer Pharma GmbH, Lorex, National Alliance for Research on Schizophrenia and Depression, NCCAM, NIDA, NIMH, Novartis, Organon, Pamlab, Pfizer, Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay, Synthelabo, and Wyeth-Ayerst Laboratories; has served as an advisor and consultant to Abbott, Affectis Pharmaceuticals AG, Amarin, Aspect Medical Systems, AstraZeneca, Auspex, Bayer AG, Best Practice Project Management, BioMarin, Biovail, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress, Dov, Eisai, Eli Lilly, EPIX, Euthymics Bioscience, Fabre-Kramer, Forest, GlaxoSmithKline, Grunenthal GmbH, Janssen, Jazz, Johnson & Johnson, Knoll, Labopharm, Lorex, Lundbeck, MedAvate, Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, Pamlab, Pfizer, PharmaStar, Pharmavite, Precision Human Biolaboratory, Prexa, PsychoGenics, Psylin Neurosciences, Ridge Diagnostics, Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay, Somaxon, Somerset, Synthelabo, Takeda, Tetragenex, TransForm, Transcept, Vanda, and Wyeth-Ayerst; has received speaking and publishing honoraria from Adamed, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Imedex, Novartis, Organon, Pfizer, PharmaStar, MGH Psychiatry Academy/Primedia, MGH Psychiatry Academy/Reed-Elsevier, United Biosource Corporation, and Wyeth-Ayerst; holds equity in Compellis; currently holds a patent for sequential parallel comparison design and a patent application for a combination of azapirones and bupropion in major depressive disorder; and has received copyright royalties for the MGH Cognitive and Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs and Symptoms, and SAFER diagnostic instruments. Drs Levy, Pet, Hsieh, and Pencina and Mr Ward have no competing interests. NR 16 TC 12 Z9 12 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2012 VL 73 IS 3 BP 353 EP 357 DI 10.4088/JCP.10m06541 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 916OV UT WOS:000302114000011 PM 21939613 ER PT J AU Biederman, J Petty, CR Woodworth, KY Lomedico, A O'Connor, KB Wozniak, J Faraone, SV AF Biederman, Joseph Petty, Carter R. Woodworth, K. Yvonne Lomedico, Alexandra O'Connor, Katherine B. Wozniak, Janet Faraone, Stephen V. TI How Informative Are Open-Label Studies for Youth With Bipolar Disorder? A Meta-Analysis Comparing Open-Label Versus Randomized, Placebo-Controlled Clinical Trials SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PHARMACOLOGICAL-TREATMENT; OLANZAPINE MONOTHERAPY; DOUBLE-BLIND; CHILDREN; ADOLESCENTS; MANIA; ARIPIPRAZOLE; RISPERIDONE; DIVALPROEX AB Objective: To examine the informativeness of open-label trials toward predicting results in subsequent randomized, placebo-controlled clinical trials of psychopharmacologic treatments for pediatric bipolar disorder. Data Sources: We searched journal articles through PubMed at the National Library of Medicine using bipolar disorder, mania, pharmacotherapy, treatment and clinical trial as keywords. This search was supplemented with scientific presentations at national and international scientific meetings and submitted manuscripts from our group. Study Selection: Selection criteria included (1) enrollment of children diagnosed with DSM-IV bipolar disorder; (2) prospective assessment of at least 3 weeks; (3) monotherapy of a pharmacologic treatment for bipolar disorder; (4) use of a randomized placebo-controlled design or an open-label design for the same therapeutic compound; and (5) repeated use of the Young Mania Rating Scale (YMRS) as an outcome. Data Extraction:The following information and data were extracted from 14 studies: study design, name of medication, class of medication, dose of medication, sample size, age, sex, trial length, and YMRS mean and standard deviation baseline and follow-up scores. Results: For both study designs, the pooled effect size was statistically significant (open-label studies, z=8.88, P<.001; randomized placebo-controlled studies, z=13.75, P<.001), indicating a reduction in the YMRS from baseline to endpoint in both study designs. In a meta-analysis regression, study design was not a significant predictor of mean change in the YMRS. Conclusions: We found similarities in the treatment effects between open-label and randomized placebo-controlled studies in youth with bipolar disorder indicating that open-label studies are useful predictors of the potential safety and efficacy of a given compound in the treatment of pediatric bipolar disorder. J Clin Psychiatry 2012;73(3):358-365 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Biederman, Joseph; Petty, Carter R.; Woodworth, K. Yvonne; Lomedico, Alexandra; O'Connor, Katherine B.; Wozniak, Janet] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, Boston, MA 02114 USA. [Biederman, Joseph; Wozniak, Janet] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Neurosci, Syracuse, NY USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol & Adult, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU ElMindA; Janssen; McNeil; Next Wave Pharmaceuticals; Shire; Eli Lilly; AstraZeneca; Fundacion Dr Manuel Camelo A.C. in Monterrey Mexico; Fundacion Areces (Spain); Medice Pharmaceuticals (Germany); Spanish Child Psychiatry Association; Abbott; Alza; Bristol-Myers Squibb; Celltech; Cephalon; Esai; Forest; Glaxo; Gliatech; Merck; National Alliance for Research on Schizophrenia and Depression (NARSAD); National Institute on Drug Abuse; New River; National Institute of Child Health and Development; National Institute of Mental Health (NIMH); Novartis; Noven; Neurosearch; Organon; Otsuka; Pfizer; Pharmacia; Prechter Foundation; Stanley Foundation; UCB Pharma; Wyeth; Boehringer-Ingelheim; Schwarz-Pharma; Pediatric Psychopharmacology Council FX Dr Biederman is currently receiving research support from ElMindA, Janssen, McNeil, Next Wave Pharmaceuticals, and Shire. In 2011, he gave a single unpaid talk for Juste Pharmaceutical Spain; received honoraria from the Massachusetts General Hospital (MGH) Psychiatry Academy for a tuition-funded continuing medical education (CME) course and from Cambridge University Press for a chapter publication; and received departmental royalties-which were paid by Eli Lilly, Shire, and AstraZeneca and paid to the Department of Psychiatry at MGH-from a copyrighted rating scale used for attention-deficit/hyperactivity disorder diagnoses. In 2010, he received a speaker's fee from a single talk given at Fundacion Dr Manuel Camelo A.C. in Monterrey Mexico; provided single consultations, which were paid to the Department of Psychiatry at MGH, for Shionogi Pharma and Cipher Pharmaceuticals; and received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In 2009, he received a speaker's fee from Fundacion Areces (Spain), Medice Pharmaceuticals (Germany), and the Spanish Child Psychiatry Association. In previous years, he received research support, consultation fees, or speaker's fees for/from Abbott, Alza, AstraZeneca, Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly, Esai, Forest, Glaxo, Gliatech, Janssen, McNeil, Merck, National Alliance for Research on Schizophrenia and Depression (NARSAD), National Institute on Drug Abuse, New River, National Institute of Child Health and Development, National Institute of Mental Health (NIMH), Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Prechter Foundation, Shire, Stanley Foundation, UCB Pharma, and Wyeth. Dr Wozniak is the author of the book Is Your Child Bipolar? published May 2009, Bantam Books. She has been a consultant to Pfizer, Shire, and Eli Lilly; has received research funding from Eli Lilly and NIMH; and has served on speakers bureaus of Eli Lilly and Janssen. Her spouse, John Winkelman, MD, PhD, has been on the speakers bureau for Cephalon, Sanofi-Aventis, Sepracor, GlaxoSmith Kline, and Takeda; has served on advisory boards for Pfizer, GlaxoSmithKline, Sepracor, Schwarz-Pharma, Takeda, and Boehringer-Ingelheim, and has received research support from Pfizer, GlaxoSmithKline, UCB Pharma, Boehringer-Ingelheim, and Schwarz-Pharma. Dr. Faraone receives royalties from a book published by Guilford Press: Straight Talk about Your Child's Mental Health. In the past year, he has received consulting fees and was on advisory boards for Shire Development and has received research support from Shire and National Institutes of Health (NIH). In previous years, he has received consulting fees, was on advisory boards, or participated in CME programs sponsored by Shire, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly and has received research support from Eli Lilly, Shire, Pfizer, and NIH. Mr Petty and Mss Woodworth, Lomedico, and O'Connor report no conflicts of interests.; This work was supported in part by the Pediatric Psychopharmacology Council Fund. NR 28 TC 6 Z9 6 U1 3 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2012 VL 73 IS 3 BP 358 EP 365 DI 10.4088/JCP.10m06490 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 916OV UT WOS:000302114000012 PM 22154898 ER PT J AU Silva, MJB Kajiya, M AlShwaimi, E Sasaki, H Hong, JN Ok, P Rezende, TMB Pagonis, TC White, RR Paster, BJ Stashenko, P Kawai, T AF Silva, Marcelo J. B. Kajiya, Mikihito AlShwaimi, Emad Sasaki, Hajime Hong, Jennifer Ok, Peter Rezende, Taia M. B. Pagonis, Tom C. White, Robert R. Paster, Bruce J. Stashenko, Philip Kawai, Toshihisa TI Bacteria-reactive Immune Response May Induce RANKL-expressing T Cells in the Mouse Periapical Bone Loss Lesion SO JOURNAL OF ENDODONTICS LA English DT Article DE Bacterial infectcion; memory T cell; periapical bone lesion; RANKL ID KAPPA-B-LIGAND; APICAL PERIODONTITIS; RECEPTOR ACTIVATOR; OSTEOPROTEGERIN; LYMPHOCYTE; KINETICS; TEETH AB Introduction: The present study investigated whether bacteria infecting the root canal can activate any infiltrating T cells to produce receptor activator of nuclear factor kappa B (NF-kappa B) ligand (RANKL). Methods: Using a mouse model of periapical lesion induced by artificial dental pulp exposure, the presence of RANKLpositive T cells and osteoclasts in the periapical lesion was examined by an immunohistochemical approach. The bacteria colonizing the exposed root canal were identified by 16S ribosomal RNA (rRNA) sequence analysis. The isolated endodontic bacteria were further immunized to normal mice, and soluble activator of NF-kappa B ligand (sRANKL) production by the T cells isolated from the immunized mice was evaluated by ex vivo culture system. Results: RANKL-positive T cells along with TRAP+ osteoclasts were identified in periapical bone resorption lesions. The gram-negative bacterium Pasteurella pnumotropica, which was most frequently detected from the root canal of exposed pulp, showed remarkably elevated serum immunoglobulin G (IgG)-antibody response in pulp-exposed mice compared with control nontreated mice. Immunization of mice with P pneumotropica induced not only serum IgG-antibody but also primed bacteria-reactive T cells that produced sRANKL in response to ex vivo exposure to P pneumotropica. Conclusions: T cells infiltrating the periapical region express RANKL, and the endodontic bacteria colonizing the root canal appear to induce RANKL expression from bacteria-reactive T cells, suggesting the possible pathogenic engagement of the immune response to endodontic bacteria in the context of developing bone resorptive periapical lesions. (J Endod 2012;38:346-350) C1 [Silva, Marcelo J. B.; Kajiya, Mikihito; Hong, Jennifer; Ok, Peter; Rezende, Taia M. B.; Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Cambridge, MA 02142 USA. [AlShwaimi, Emad; Sasaki, Hajime; Stashenko, Philip] Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02142 USA. [Paster, Bruce J.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Hong, Jennifer; Ok, Peter; Pagonis, Tom C.; White, Robert R.] Harvard Univ, Sch Dent Med, Dept Restorat Dent & Biomat Sci, Div Endodont, Boston, MA 02115 USA. [Kajiya, Mikihito; Sasaki, Hajime; Paster, Bruce J.; Stashenko, Philip; Kawai, Toshihisa] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Silva, Marcelo J. B.] Univ Fed Uberlandia, Lab Immunoparasitol, Inst Biomed Sci, BR-38400 Uberlandia, MG, Brazil. [AlShwaimi, Emad] Univ Dammam, Restorat Dent Sci Dept, Coll Dent, Dammam, Saudi Arabia. [Rezende, Taia M. B.] Univ Catolica Brasilia, Curso Odontol & Posgrad Ciencias Genom & Biotecno, Brasilia, DF, Brazil. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 245 1st St, Cambridge, MA 02142 USA. EM tkawai@forsyth.org RI AlShwaimi, Emad /F-4077-2012; Rezende, Taia/D-3732-2015; Silva, Marcelo/J-4298-2012 OI Silva, Marcelo/0000-0002-5807-4286 FU NIDCR NIH HHS [R01 DE003420, R01 DE018499-04, R01 DE018499, DE-18499, R01 DE019917, DE-19917, R37 DE003420, R01 DE019917-03] NR 22 TC 15 Z9 15 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD MAR PY 2012 VL 38 IS 3 BP 346 EP 350 DI 10.1016/j.joen.2011.12.029 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 912UJ UT WOS:000301826600014 PM 22341072 ER PT J AU Mizukami, Y AF Mizukami, Yusuke TI Bone marrow-derived proangiogenic cells in pancreatic cancer SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE angiogenesis; bone marrow-derived cell; hedgehog; pancreatic cancer ID ENDOTHELIAL GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; PHASE-III TRIAL; SONIC HEDGEHOG; TUMOR-GROWTH; PROGENITOR CELLS; MYOFIBROBLASTS CONTRIBUTE; DUCTAL ADENOCARCINOMA; STELLATE CELLS; THERAPY AB Tumor-derived signals systemically induce an angiogenic switch that allows cancer cells to survive and grow. However, the vascular network in tumors is not well organized and fails to meet metabolic needs to maintain tissue homeostasis, resulting in significant hypoxia. Among various tumors, pancreatic ductal adenocarcinoma (PDAC) typically develops in an unusually disordered microenvironment, which contributes to its highly aggressive behavior. Since anti-vascular endothelial growth factor (VEGF) (Avastin) has failed to demonstrate a survival benefit in PDAC, we need to re-visit the basic biology of this disease and understand what makes it so refractory to the anti-angiogenic approaches that are clinically effective in other neoplasms. To address this issue, we specifically focused on the process of neovascularization where bone marrow-derived cells (BMDCs) play a role during pancreatic tumorigenesis. We have identified subsets of BMDCs that regulate key processes during development of the neovessels through paracrine Hedgehog signaling. Considering the importance of systemic responses occurring in tumor bearing hosts, we are currently using genetically engineered mice, which spontaneously develop PDAC, Pdx1-Cre;LSL-KrasG12D;p53lox/+ strain, to clarify critical events that can trigger aberrant angiogenesis in pancreatic cancer. These studies allow us to provide insights into the cellular and molecular mechanisms of pancreatic tumorigenesis and have an implication for the design of therapies against this difficult disease. C1 [Mizukami, Yusuke] Sapporo Higashi Tokushukai Hosp, Ctr Clin & Biomed Res, Sapporo, Hokkaido, Japan. [Mizukami, Yusuke] Asahikawa Med Univ, Dept Med, Asahikawa, Hokkaido, Japan. [Mizukami, Yusuke] Massachusetts Gen Hosp, Ctr Canc Res, Gastrointestinal Unit, Boston, MA 02114 USA. [Mizukami, Yusuke] Harvard Univ, Sch Med, Boston, MA USA. RP Mizukami, Y (reprint author), Sapporo Higashi Tokusyukai Hosp, Ctr Clin & Biomed Res, 3-1,North 33,East 14, Sapporo, Hokkaido 0650033, Japan. EM ymizu1968@gmail.com NR 50 TC 2 Z9 2 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2012 VL 27 SU 2 SI SI BP 23 EP 26 DI 10.1111/j.1440-1746.2011.07012.x PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 889AX UT WOS:000300047000006 PM 22320912 ER PT J AU Gukovsky, I Pandol, SJ Mareninova, OA Shalbueva, N Jia, WZ Gukovskaya, AS AF Gukovsky, Ilya Pandol, Stephen J. Mareninova, Olga A. Shalbueva, Natalia Jia, Wenzhuo Gukovskaya, Anna S. TI Impaired autophagy and organellar dysfunction in pancreatitis SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE cathepsin; lysosome-associated membrane protein; lysosome; pancreatic mitochondria; permeability transition pore ID KEY PATHOLOGICAL RESPONSES; KAPPA-B ACTIVATION; CELL-DEATH; ACINAR-CELLS; PERMEABILITY TRANSITION; TRYPSINOGEN ACTIVATION; MITOCHONDRIA; PATHOGENESIS; MECHANISMS; PATHWAYS AB Recent findings from our group, obtained on experimental in vivo and ex vivo models of pancreatitis, reveal that this disease causes a profound dysfunction of key cellular organelles, lysosomes and mitochondria. We found that autophagy, the main cellular degradative, lysosome-driven process, is activated but also impaired in acute pancreatitis because of its' inefficient progression/resolution (flux) resulting from defective function of lysosomes. One mechanism underlying the lysosomal dysfunction in pancreatitis is abnormal processing (maturation) and activation of cathepsins, major lysosomal hydrolases; another is a decrease in pancreatic levels of key lysosomal membrane proteins LAMP-1 and LAMP-2. Our data indicate that lysosomal dysfunction plays an important initiating role in pancreatitis pathobiology. The impaired autophagy mediates vacuole accumulation in acinar cells; furthermore, the abnormal maturation and activation of cathepsins leads to increase in intra-acinar trypsin, the hallmark of pancreatitis; and LAMP-2 deficiency causes inflammation and acinar cell necrosis. Thus, the autophagic and lysosomal dysfunctions mediate key pathologic responses of pancreatitis. On the other hand, we showed that pancreatitis causes acinar cell mitochondria depolarization, mediated by the permeability transition pore (PTP). Genetic (via deletion of cyclophilin D) inactivation of PTP prevents mitochondrial depolarization and greatly ameliorates the pathologic responses of pancreatitis. Further, our data suggest that mitochondrial damage, by stimulating autophagy, increases the demand for efficient lysosomal degradation and therefore aggravates the pathologic consequences of lysosomal dysfunction. Thus, the combined autophagic, lysosomal and mitochondrial dysfunctions are key to the pathogenesis of pancreatitis. C1 [Gukovsky, Ilya; Pandol, Stephen J.; Mareninova, Olga A.; Shalbueva, Natalia; Gukovskaya, Anna S.] VA Greater Los Angeles Healthcare Syst, So Calif Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. [Gukovsky, Ilya; Pandol, Stephen J.; Mareninova, Olga A.; Shalbueva, Natalia; Gukovskaya, Anna S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Jia, Wenzhuo] Beijing Hosp, Beijing, Peoples R China. [Gukovsky, Ilya; Pandol, Stephen J.; Mareninova, Olga A.; Shalbueva, Natalia; Gukovskaya, Anna S.] VA Greater Los Angeles Healthcare Syst, So Calif Res Ctr Cirrhosis, Los Angeles, CA USA. RP Gukovskaya, AS (reprint author), UCLA VA Greater Los Angeles, W Los Angeles VA Healthcare Ctr, Pancreat Res Grp, 11308 Wilshire Blvd,Blg 258,Rm 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NCI NIH HHS [P01 CA163200]; NIAAA NIH HHS [P50 AA011999-09, AA19730, R01 AA019730-01A1, P50AA11999, R01 AA019730, P50 AA011999]; NIDDK NIH HHS [R01 DK059936-09, DK59936, R01 DK059936] NR 51 TC 41 Z9 44 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 2012 VL 27 SU 2 SI SI BP 27 EP 32 DI 10.1111/j.1440-1746.2011.07004.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 889AX UT WOS:000300047000007 PM 22320913 ER PT J AU Jha, AK Epstein, AM AF Jha, Ashish K. Epstein, Arnold M. TI Governance Around Quality of Care at Hospitals that Disproportionately Care for Black Patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE quality of care; disparities; quality improvement ID DISPARITIES; PERFORMANCE; MEDICARE; TRENDS AB BACKGROUND: Hospital boards of directors can play a pivotal role in improving care, yet we know little about how the boards of hospitals that disproportionately serve minority patients engage in this issue. OBJECTIVES: To examine how boards of directors at black-serving hospitals are engaged in quality of care issues and compare priorities and practices of black-serving and non-black-serving hospital boards. DESIGN: We identified all nonprofit U. S. hospitals in the top decile of proportion of elderly black patients ("black-serving") and surveyed their board chairpersons and a national sample of chairpersons from other nonprofit U. S. hospitals ("non-black-serving"). PARTICIPANTS: Board chairpersons of black-serving and non-black-serving U. S. hospitals. MAIN MEASURES: Board chairpersons' familiarity and expertise with quality of care issues, level of engagement with quality management, prioritization of quality issues, and efforts to improve quality or to reduce racial disparities in the quality of care. KEY RESULTS: We received responses from 79% of black-serving hospitals and 78% of non-black-serving hospitals. We found that board chairpersons from black-serving hospitals less often reported having at least moderate expertise in quality of care (68% versus 79%, P=0.04) or rating it as one of the top two priorities for board oversight (48% versus 57%, P=0.09) or for CEO performance evaluation (40% versus 50%, P=0.05). Only 14.2% of board chairpersons from black-serving hospitals (and 7.7% of non-black-serving hospitals) agreed with the statement that disparities exist among my hospital patients, although less than 10% of all board chairpersons reported examining quality or patient satisfaction data stratified by race. CONCLUSIONS: Board chairpersons of black-serving hospitals report less expertise with quality of care issues and are less likely to give high priority to these issues than board chairpersons of non-black-serving hospitals. Interventions to engage and educate board members in issues of quality and racial disparities may be needed to improve quality and reduce disparities in care. C1 [Jha, Ashish K.; Epstein, Arnold M.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Jha, Ashish K.; Epstein, Arnold M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu FU Hauser Center for Nonprofit Organizations at Harvard University; Rx Foundation, Cambridge, MA FX The project was funded by the Hauser Center for Nonprofit Organizations at Harvard University and the Rx Foundation, Cambridge, MA. NR 16 TC 8 Z9 8 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2012 VL 27 IS 3 BP 297 EP 303 DI 10.1007/s11606-011-1880-9 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 912YP UT WOS:000301838500010 PM 21948204 ER PT J AU Yano, EM Chaney, EF Campbell, DG Klap, R Simon, BF Bonner, LM Lanto, AB Rubenstein, LV AF Yano, Elizabeth M. Chaney, Edmund F. Campbell, Duncan G. Klap, Ruth Simon, Barbara F. Bonner, Laura M. Lanto, Andrew B. Rubenstein, Lisa V. TI Yield of Practice-Based Depression Screening In VA Primary Care Settings SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE depression; screening; primary care; health care delivery; veterans ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL-COMORBIDITY-SURVEY; IDENTIFICATION TEST AUDIT; ALCOHOL-USE DISORDERS; MENTAL-HEALTH; MAJOR DEPRESSION; COLLABORATIVE MANAGEMENT; MEDICAL OUTPATIENTS; SUICIDAL IDEATION; UNITED-STATES AB BACKGROUND: Many patients who should be treated for depression are missed without effective routine screening in primary care (PC) settings. Yearly depression screening by PC staff is mandated in the VA, yet little is known about the expected yield from such screening when administered on a practice-wide basis. OBJECTIVE: We characterized the yield of practice-based screening in diverse PC settings, as well as the care needs of those assessed as having depression. DESIGN: Baseline enrollees in a group randomized trial of implementation of collaborative care for depression. PARTICIPANTS: Randomly sampled patients with a scheduled PC appointment in ten VA primary care clinics spanning five states. MEASUREMENTS: PHQ-2 screening followed by the full PHQ-9 for screen positives, with standardized sociodemographic and health status questions. RESULTS: Practice-based screening of 10,929 patients yielded 20.1% positive screens, 60% of whom were assessed as having probable major depression based on the PHQ-9 (11.8% of all screens) (n=1,313). In total, 761 patients with probable major depression completed the baseline assessment. Comorbid mental illnesses (e. g., anxiety, PTSD) were highly prevalent. Medical comorbidities were substantial, including chronic lung disease, pneumonia, diabetes, heart attack, heart failure, cancer and stroke. Nearly one-third of the depressed PC patients reported recent suicidal ideation (based on the PHQ-9). Sexual dysfunction was also common (73.3%), being both longstanding (95.1% with onset >6 months) and frequently undiscussed and untreated (46.7% discussed with any health care provider in past 6 months). CONCLUSIONS: Practice-wide survey-based depression screening yielded more than twice the positive-screen rate demonstrated through chart-based VA performance measures. The substantial level of comorbid physical and mental illness among PC patients precludes solo management by either PC or mental health (MH) specialists. PC practice-and provider-level guideline adherence is problematic without systems-level solutions supporting adequate MH assessment, PC treatment and, when needed, appropriate MH referral. C1 [Yano, Elizabeth M.; Klap, Ruth; Simon, Barbara F.; Lanto, Andrew B.; Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, VA Greater Los Angeles Ctr Excellence Study Healt, Sepulveda, CA USA. [Yano, Elizabeth M.; Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Sci, Los Angeles, CA 90024 USA. [Chaney, Edmund F.; Bonner, Laura M.] VA Puget Sound Healthcare Syst, NW Ctr Outcomes Res, VA HSR&D Ctr Excellence, Seattle, WA USA. [Chaney, Edmund F.; Bonner, Laura M.] Univ Washington, Seattle, WA 98195 USA. [Campbell, Duncan G.] Univ Montana, Dept Psychol, Missoula, MT 59812 USA. [Rubenstein, Lisa V.] VA Greater Los Angeles Healthcare Syst, Dept Med, Sepulveda, CA USA. [Rubenstein, Lisa V.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Rubenstein, Lisa V.] RAND Hlth, Santa Monica, CA USA. RP Yano, EM (reprint author), VA Greater Los Angeles HSRD Ctr Excellence, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM elizabeth.yano@va.gov FU Department of Veterans Affairs (VA) Health Services Research and Development (HSRD) Service; Quality Enhancement Research Initiative (QUERI) [MHI 99-375, MNT 01-027]; VA HSRD [05-195]; VA Office of Academic Affiliations (OAA) at the Northwest Center for Outcomes Research FX This project was funded by the Department of Veterans Affairs (VA) Health Services Research and Development (HSR&D) Service and the Quality Enhancement Research Initiative (QUERI) (Project #MHI 99-375 and MNT 01-027). The manuscript reflects baseline data from a group randomized trial (Trial Registration No. NCT00105820). Dr. Yano is funded under a VA HSR&D Research Career Scientist award (Project #05-195). Dr. Campbell was funded by a VA Office of Academic Affiliations (OAA) Associated Health Postdoctoral Fellowship Program at the Northwest Center for Outcomes Research at the time the study was conducted; he is now Assistant Professor at the University of Montana. NR 65 TC 16 Z9 16 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2012 VL 27 IS 3 BP 331 EP 338 DI 10.1007/s11606-011-1904-5 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 912YP UT WOS:000301838500015 PM 21975821 ER PT J AU Bowden, MG Behrman, AL Woodbury, M Gregory, CM Velozo, CA Kautz, SA AF Bowden, Mark G. Behrman, Andrea L. Woodbury, Michelle Gregory, Chris M. Velozo, Craig A. Kautz, Steven A. TI Advancing Measurement of Locomotor Rehabilitation Outcomes to Optimize Interventions and Differentiate Between Recovery Versus Compensation SO JOURNAL OF NEUROLOGIC PHYSICAL THERAPY LA English DT Article DE measurement; rehabilitation; walking ID SPINAL-CORD-INJURY; RANDOMIZED CONTROLLED-TRIAL; CHRONIC STROKE SURVIVORS; GROUND REACTION FORCES; STEP ACTIVITY MONITOR; BODY-WEIGHT SUPPORT; AMBULATORY ACTIVITY; HEMIPARETIC WALKING; CLINICAL-TRIAL; MOTOR CONTROL AB Progress in locomotor rehabilitation has created an increasing need to understand the factors that contribute to motor behavior, to determine whether these factors are modifiable, and if so, to determine how best to modify them in a way that promotes improved function. Currently available clinical measures do not have the capacity to distinguish between neuromotor recovery and compensation for impaired underlying body structure/functions. This Special Interest article examines the state of outcomes measurement in physical therapy in regard to locomotor rehabilitation, and suggests approaches that may improve assessment of recovery and clinical decision-making capabilities. We examine historical approaches to measurement of locomotor rehabilitation outcomes, including rating scales, timed movement tasks, and laboratory-based outcome measures, and we discuss the emerging use of portable technology to assess walking in a free-living environment. The ability to accurately measure outcomes of rehabilitation, both in and away from the clinical/laboratory setting, allows assessment of skill acquisition, retention, and long-term carryover in a variety of environments. Accurate measurement allows behavioral changes to be observed, and assessments to be made, regarding an individual's ability to adapt during interventions and to incorporate new skills into real-world behaviors. The result of such an approach to assessment may be that interventions truly translate from clinical/laboratory to real-world environments. Future locomotor measurement tools must be based on a theoretical framework that can guide their use to accurately quantify treatment effects and provide a basis upon which to develop and refine therapeutic interventions. C1 [Bowden, Mark G.; Woodbury, Michelle; Gregory, Chris M.; Kautz, Steven A.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Bowden, Mark G.; Woodbury, Michelle; Gregory, Chris M.; Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC USA. [Behrman, Andrea L.] Univ Florida, Dept Phys Therapy, Gainesville, FL USA. [Velozo, Craig A.] Univ Florida, Dept Occupat Therapy, NF SG Vet Hlth Syst, Gainesville, FL USA. RP Bowden, MG (reprint author), 77 President St,MSC 700, Charleston, SC 29425 USA. EM bowdenm@musc.edu OI Kautz, Steven/0000-0003-3151-8235 FU VA Career Development Award (Phase I) [B7177]; National Institutes of Health National Center for Medical and Rehabilitation Research (NICHD) [KI2 HD055929]; National Institute for Neurological Disorders Stroke; VA Merit Review [B3983-R]; VA Center of Excellence [F2182C] FX Funding : VA Career Development Award (Phase I): B7177; KI2 HD055929 National Institutes of Health National Center for Medical and Rehabilitation Research (NICHD) and National Institute for Neurological Disorders & Stroke; VA Merit Review grant B3983-R; and VA Center of Excellence grant #F2182C (Brain Rehabilitation Research Center). NR 59 TC 12 Z9 12 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1557-0576 J9 J NEUROL PHYS THER JI J. Neurol. Phys. Ther. PD MAR PY 2012 VL 36 IS 1 BP 38 EP 44 DI 10.1097/NPT.0b013e3182472cf6 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 915CS UT WOS:000302001500007 PM 22333921 ER PT J AU Lilaonitkul, W Guinan, JJ AF Lilaonitkul, Watjana Guinan, John J., Jr. TI Frequency tuning of medial-olivocochlear-efferent acoustic reflexes in humans as functions of probe frequency SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE hearing; cochlear amplifier; masking; tuning curves; otoacoustic emissions ID AUDITORY-NERVE-FIBER; EVOKED OTOACOUSTIC EMISSIONS; COCHLEAR HAIR-CELLS; GUINEA-PIG COCHLEA; ELECTRICAL-STIMULATION; CONTRALATERAL SOUND; RESPONSE PROPERTIES; STIMULUS VARIABLES; VISUAL-ATTENTION; FINE-STRUCTURE AB Lilaonitkul W, Guinan JJ Jr. Frequency tuning of medial-olivocochlear-efferent acoustic reflexes in humans as functions of probe frequency. J Neurophysiol 107: 1598-1611, 2012. First published December 21, 2011; doi:10.1152/jn.00549.2011.-The medial-olivocochlear (MOC) acoustic reflex is thought to provide frequency-specific feedback that adjusts the gain of cochlear amplification, but little is known about how frequency specific the reflex actually is. We measured human MOC tuning through changes in stimulus frequency otoacoustic emissions (SFOAEs) from 40-dB-SPL tones at probe frequencies (f(p)s) near 0.5, 1.0, and 4.0 kHz. MOC activity was elicited by 60-dB-SPL ipsilateral, contralateral, or bilateral tones or half-octave noise bands, with elicitor frequency (f(e)) varied in half-octave steps. Tone and noise elicitors produced similar results. At all probe frequencies, SFOAE changes were produced by a wide range of elicitor frequencies with elicitor frequencies near 0.7-2.0 kHz being particularly effective. MOC-induced changes in SFOAE magnitude and SFOAE phase were surprisingly different functions of f(e): magnitude inhibition largest for f(e) close to f(p), phase change largest for f(e) remote from f(p). The metric Delta SFOAE, which combines both magnitude and phase changes, provided the best match to reported (cat) MOC neural inhibition. Ipsilateral and contralateral MOC reflexes often showed dramatic differences in plots of MOC effect vs. elicitor frequency, indicating that the contralateral reflex does not give an accurate picture of ipsilateral-reflex properties. These differences in MOC effects appear to imply that ipsilateral and contralateral reflexes have different actions in the cochlea. The implication of these results for MOC function, cochlear mechanics, and the production of SFOAEs are discussed. C1 [Lilaonitkul, Watjana; Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Lilaonitkul, Watjana] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Guinan, John J., Jr.] Harvard Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM John_Guinan@meei.harvard.edu FU National Institute of Deafness and Other Communication Disorders [RO1 DC-005977, P30 DC-05029] FX This work was supported by National Institute of Deafness and Other Communication Disorders Grants RO1 DC-005977 and P30 DC-05029. NR 72 TC 19 Z9 19 U1 1 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 2012 VL 107 IS 6 BP 1598 EP 1611 DI 10.1152/jn.00549.2011 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 916YY UT WOS:000302140300007 PM 22190630 ER PT J AU Schiffenbauer, AI Wahl, C Pittaluga, S Jaffe, ES Hoffman, R Khosroshahi, A Stone, JH Deshpande, V Gahl, WA Gill, F AF Schiffenbauer, Adam I. Wahl, Colleen Pittaluga, Stefania Jaffe, Elaine S. Hoffman, Ronald Khosroshahi, Arezou Stone, John H. Deshpande, Vikram Gahl, William A. Gill, Fred TI IgG4-related disease presenting as recurrent mastoiditis SO LARYNGOSCOPE LA English DT Editorial Material ID SYSTEMIC-DISEASE; SCLEROSING DISEASE C1 [Wahl, Colleen; Gahl, William A.; Gill, Fred] NHGRI, NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Pittaluga, Stefania; Jaffe, Elaine S.] NHGRI, Pathol Lab, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Gill, Fred] NHGRI, Internal Med Consult Serv, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Gahl, William A.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Schiffenbauer, Adam I.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Hoffman, Ronald] New York Eye & Ear Infirm, Ear Inst, New York, NY 10003 USA. [Khosroshahi, Arezou; Stone, John H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Rheumatol Unit, Boston, MA USA. [Deshpande, Vikram] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Schiffenbauer, AI (reprint author), NIH, Ctr Clin, Bldg 10,Room 6N216A,10 Ctr Dr, Bethesda, MD 20892 USA. EM adam.schiffenbauer@nih.gov OI Jaffe, Elaine/0000-0003-4632-0301; Schiffenbauer, Adam/0000-0001-9964-9966 FU Intramural NIH HHS [Z99 AR999999] NR 12 TC 15 Z9 16 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 2012 VL 122 IS 3 BP 681 EP 684 DI 10.1002/lary.22486 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 897TN UT WOS:000300680200033 PM 22252885 ER PT J AU Wu, QH Xuan, WJ Ando, T Xu, T Huang, LY Huang, YY Dai, TH Dhital, S Sharma, SK Whalen, MJ Hamblin, MR AF Wu, Qiuhe Xuan, Weijun Ando, Takahiro Xu, Tao Huang, Liyi Huang, Ying-Ying Dai, Tianghong Dhital, Saphala Sharma, Sulbha K. Whalen, Michael J. Hamblin, Michael R. TI Low-Level Laser Therapy for Closed-Head Traumatic Brain Injury in Mice: Effect of Different Wavelengths SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE photobiomodulation; low-level laser therapy; traumatic brain injury; mouse model; Neurological Severity Score ID TERM NEUROLOGICAL DEFICITS; CYTOCHROME-C-OXIDASE; TRANSCRANIAL LASER; CEREBRAL-ISCHEMIA; UNITED-STATES; IR RADIATION; SPINAL-CORD; STROKE; PHOTOTHERAPY; LIGHT AB Background and Objectives Traumatic brain injury (TBI) affects millions worldwide and is without effective treatment. One area that is attracting growing interest is the use of transcranial low-level laser therapy (LLLT) to treat TBI. The fact that near-infrared light can penetrate into the brain would allow non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. LLLT may treat TBI by increasing respiration in the mitochondria, causing activation of transcription factors, reducing inflammatory mediators and oxidative stress, and inhibiting apoptosis. Study Design/Materials and Methods: We tested LLLT in a mouse model of closed-head TBI produced by a controlled weight drop onto the skull. Mice received a single treatment with continuous-wave 665, 730, 810, or 980 nm lasers (36 J/cm(2) delivered at 150 mW/cm(2)) 4-hour post-TBI and were followed up by neurological performance testing for 4 weeks. Results: Mice with moderate-to-severe TBI treated with 665 and 810 nm laser (but not with 730 or 980 nm) had a significant improvement in Neurological Severity Score that increased over the course of the follow-up compared to sham-treated controls. Morphometry of brain sections showed a reduction in small deficits in 665 and 810 nm laser treated mouse brains at 28 days. Conclusions: The effectiveness of 810 nm agrees with previous publications, and together with the effectiveness of 660 nm and non-effectiveness of 730 and 980 nm can be explained by the absorption spectrum of cytochrome oxidase, the candidate mitochondrial chromophore in transcranial LLLT. Lasers Surg. Med. 44: 218-226, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Wu, Qiuhe; Xuan, Weijun; Ando, Takahiro; Xu, Tao; Huang, Liyi; Huang, Ying-Ying; Dai, Tianghong; Dhital, Saphala; Sharma, Sulbha K.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Wu, Qiuhe; Xuan, Weijun; Xu, Tao; Huang, Liyi; Huang, Ying-Ying; Dai, Tianghong; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Wu, Qiuhe] Shandong Univ, Dept Burns & Plast Surg, Jinan Cent Hosp, Jinan 250100, Peoples R China. [Xuan, Weijun] Tradit Chinese Med Univ Guangxi, Dept Otolaryngol, Nanning, Peoples R China. [Ando, Takahiro] Keio Univ, Dept Elect & Elect Engn, Kohoku Ku, Yokohama, Kanagawa 2238522, Japan. [Xu, Tao] Shanghai Jiao Tong Univ, Lab Anesthesiol, Shanghai, Peoples R China. [Huang, Liyi] Guangxi Med Univ, Dept Infect Dis, Affiliated Coll & Hosp 1, Nanning, Peoples R China. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Dhital, Saphala] Univ Tokyo, Dept Microbiol, Tokyo, Japan. [Whalen, Michael J.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Dhital, Saphala/0000-0001-5566-0733; Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01AI050875] NR 49 TC 37 Z9 40 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2012 VL 44 IS 3 BP 218 EP 226 DI 10.1002/lsm.22003 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA 909NZ UT WOS:000301572700005 PM 22275301 ER PT J AU Kodituwakku, S Lazar, SW Indic, P Chen, Z Brown, EN Barbieri, R AF Kodituwakku, Sandun Lazar, Sara W. Indic, Premananda Chen, Zhe Brown, Emery N. Barbieri, Riccardo TI Point process time-frequency analysis of dynamic respiratory patterns during meditation practice SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE Respiratory sinus arrhythmia; Heart rate variability; Meditation; Point processes; Time-frequency analysis ID HEART-RATE-VARIABILITY; PARASYMPATHETIC CARDIAC CONTROL; SINUS ARRHYTHMIA; VAGAL TONE; HUMANS; MECHANISMS; PRESSURE; SLEEP; MODEL; INDEX AB Respiratory sinus arrhythmia (RSA) is largely mediated by the autonomic nervous system through its modulating influence on the heart beats. We propose a robust algorithm for quantifying instantaneous RSA as applied to heart beat intervals and respiratory recordings under dynamic breathing patterns. The blood volume pressure-derived heart beat series (pulse intervals, PIs) are modeled as an inverse Gaussian point process, with the instantaneous mean PI modeled as a bivariate regression incorporating both past PIs and respiration values observed at the beats. A point process maximum likelihood algorithm is used to estimate the model parameters, and instantaneous RSA is estimated via a frequency domain transfer function evaluated at instantaneous respiratory frequency where high coherence between respiration and PIs is observed. The model is statistically validated using Kolmogorov-Smirnov goodness-of-fit analysis, as well as independence tests. The algorithm is applied to subjects engaged in meditative practice, with distinctive dynamics in the respiration patterns elicited as a result. The presented analysis confirms the ability of the algorithm to track important changes in cardiorespiratory interactions elicited during meditation, otherwise not evidenced in control resting states, reporting statistically significant increase in RSA gain as measured by our paradigm. C1 [Kodituwakku, Sandun; Chen, Zhe; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Kodituwakku, Sandun] Australian Natl Univ, Sch Engn, Appl Signal Proc Grp, Canberra, ACT, Australia. [Lazar, Sara W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Indic, Premananda] Univ Massachusetts, Dept Neurol, Sch Med, Worcester, MA 01655 USA. [Chen, Zhe; Brown, Emery N.; Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Barbieri, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM sandun.kodituwakku@anu.edu.au; lazar@nmr.mgh.harvard.edu; premananda.indic@umassmed.edu; zhechen@mit.edu; enb@neurostat.mit.edu; barbieri@neurostat.mit.edu RI Lazar, Sara/G-3809-2012; OI Lazar, Sara/0000-0003-1126-8363; Barbieri, Riccardo/0000-0001-9381-3833; Chen, Zhe/0000-0002-6483-6056 FU National Institutes of Health (NIH) [R01-HL084502, R01-DA015644, DP1-OD003646, K01-AT00694-01] FX This work was supported by the National Institutes of Health (NIH) under Grant R01-HL084502, Grant R01-DA015644, Grant DP1-OD003646, Grant K01-AT00694-01. NR 49 TC 4 Z9 4 U1 1 U2 12 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 MAR PY 2012 VL 50 IS 3 BP 261 EP 275 DI 10.1007/s11517-012-0866-z PG 15 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 918PQ UT WOS:000302263100007 PM 22350435 ER PT J AU Roberts, DA Hansen, VN Thompson, MG Poludniowski, G Niven, A Seco, J Evans, PM AF Roberts, D. A. Hansen, V. N. Thompson, M. G. Poludniowski, G. Niven, A. Seco, J. Evans, P. M. TI Kilovoltage energy imaging with a radiotherapy linac with a continuously variable energy range SO MEDICAL PHYSICS LA English DT Article DE radiotherapy verification; radiotherapy imaging; linear accelerators; conebeam CT ID BEAM COMPUTED-TOMOGRAPHY; MEGAVOLTAGE CT SCANNER; LOW-Z TARGETS; TREATMENT VERIFICATION; GUIDED RADIOTHERAPY; RADIATION-THERAPY; CARBON TARGET; SYSTEM; OPTIMIZATION; CONTRAST AB Purpose: In this paper, the effect on image quality of significantly reducing the primary electron energy of a radiotherapy accelerator is investigated using a novel waveguide test piece. The waveguide contains a novel variable coupling device (rotovane), allowing for a wide continuously variable energy range of between 1.4 and 9 MeV suitable for both imaging and therapy. Method: Imaging at linac accelerating potentials close to 1 MV was investigated experimentally and via Monte Carlo simulations. An imaging beam line was designed, and planar and cone beam computed tomography images were obtained to enable qualitative and quantitative comparisons with kilovoltage and megavoltage imaging systems. The imaging beam had an electron energy of 1.4 MeV, which was incident on a water cooled electron window consisting of stainless steel, a 5 mm carbon electron absorber and 2.5 mm aluminium filtration. Images were acquired with an amorphous silicon detector sensitive to diagnostic x-ray energies. Results: The x-ray beam had an average energy of 220 keV and half value layer of 5.9 mm of copper. Cone beam CT images with the same contrast to noise ratio as a gantry mounted kilovoltage imaging system were obtained with doses as low as 2 cGy. This dose is equivalent to a single 6 MV portal image. While 12 times higher than a 100 kVp CBCT system (Elekta XVI), this dose is 140 times lower than a 6 MV cone beam imaging system and 6 times lower than previously published LowZ imaging beams operating at higher (4-5 MeV) energies. Conclusions: The novel coupling device provides for a wide range of electron energies that are suitable for kilovoltage quality imaging and therapy. The imaging system provides high contrast images from the therapy portal at low dose, approaching that of gantry mounted kilovoltage x-ray systems. Additionally, the system provides low dose imaging directly from the therapy portal, potentially allowing for target tracking during radiotherapy treatment. There is the scope with such a tuneable system for further energy reduction and subsequent improvement in image quality. C1 [Roberts, D. A.; Hansen, V. N.; Poludniowski, G.; Evans, P. M.] Inst Canc Res, Joint Dept Phys, Sutton SM2 5PT, Surrey, England. [Roberts, D. A.; Hansen, V. N.; Poludniowski, G.; Evans, P. M.] Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England. [Roberts, D. A.; Thompson, M. G.; Niven, A.] Elekta, Crawley RH10 9RR, W Sussex, England. [Seco, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roberts, DA (reprint author), Inst Canc Res, Joint Dept Phys, Downs Rd, Sutton SM2 5PT, Surrey, England. EM david.roberts@elekta.com RI Evans, Philip/A-6257-2009; Seco, Joao/J-4451-2012 FU Elekta; Institute of Cancer Research; Cancer Research UK [C46/A3970] FX This work is supported by Elekta and The Institute of Cancer Research. Work of the ICR radiotherapy physics group is partially supported by Cancer Research UK under programme Grant No. C46/A3970. The authors are grateful for information provided by Elekta and Perkin Elmer for the purposes of modeling the linac and detectors. They are extremely grateful to Kevin Brown, Alan Hitchings, Chris Knox, Andrew Lake, Terry Large, Carlos Sandin, and Abdul Sayeed from Elekta and to Craig Cummings, Clive Long, Nick Smith, Ellen Donovan, and Karen Rosser from the Royal Marsden for component manufacture, advice on the waveguide testing and setup, and advice on various aspects of this project and paper. NR 41 TC 6 Z9 6 U1 0 U2 7 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAR PY 2012 VL 39 IS 3 BP 1218 EP 1226 DI 10.1118/1.3681011 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 908PV UT WOS:000301503400006 PM 22380352 ER PT J AU Li, XA Alber, M Deasy, JO Jackson, A Jee, KWK Marks, LB Martel, MK Mayo, C Moiseenko, V Nahum, AE Niemierko, A Semenenko, VA Yorke, ED AF Li, X. Allen Alber, Markus Deasy, Joseph O. Jackson, Andrew Jee, Kyung-Wook Ken Marks, Lawrence B. Martel, Mary K. Mayo, Charles Moiseenko, Vitali Nahum, Alan E. Niemierko, Andrzej Semenenko, Vladimir A. Yorke, Ellen D. TI The use and QA of biologically related models for treatment planning: Short report of the TG-166 of the therapy physics committee of the AAPM(a)) SO MEDICAL PHYSICS LA English DT Article DE biologically based treatment planning; outcome modeling; planning system QA; TCP; NTCP; EUD ID INTENSITY-MODULATED RADIOTHERAPY; CONFORMAL RADIATION-THERAPY; TISSUE COMPLICATION PROBABILITIES; VOLUME HISTOGRAM ANALYSIS; PRIMARY LIVER-CARCINOMA; MULTIPLE LOCAL MINIMA; TUMOR SUBVOLUMES; DOSE-RESPONSE; IMRT OPTIMIZATION; QUALITY-ASSURANCE AB Treatment planning tools that use biologically related models for plan optimization and/or evaluation are being introduced for clinical use. A variety of dose-response models and quantities along with a series of organ-specific model parameters are included in these tools. However, due to various limitations, such as the limitations of models and available model parameters, the incomplete understanding of dose responses, and the inadequate clinical data, the use of biologically based treatment planning system (BBTPS) represents a paradigm shift and can be potentially dangerous. There will be a steep learning curve for most planners. The purpose of this task group is to address some of these relevant issues before the use of BBTPS becomes widely spread. In this report, the authors (1) discuss strategies, limitations, conditions, and cautions for using biologically based models and parameters in clinical treatment planning; (2) demonstrate the practical use of the three most commonly used commercially available BBTPS and potential dosimetric differences between biologically model based and dose-volume based treatment plan optimization and evaluation; (3) identify the desirable features and future directions in developing BBTPS; and (4) provide general guidelines and methodology for the acceptance testing, commissioning, and routine quality assurance (QA) of BBTPS. (C) 2012 American Association of Physicists in Medicine. [DOI: 10.1118/1.3685447] C1 [Li, X. Allen; Semenenko, Vladimir A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Alber, Markus] Univ Munich, Clin Radiooncol, D-72076 Tubingen, Germany. [Deasy, Joseph O.; Jackson, Andrew; Yorke, Ellen D.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Jee, Kyung-Wook Ken; Niemierko, Andrzej] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Marks, Lawrence B.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Martel, Mary K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Mayo, Charles] Mayo Clin, Rochester, MN 55905 USA. [Moiseenko, Vitali] Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. [Nahum, Alan E.] Clatterbridge Ctr Oncol, Dept Phys, Wirral CH63 4JY, Merseyside, England. RP Li, XA (reprint author), Med Coll Wisconsin, Milwaukee, WI 53226 USA. EM ali@mcw.edu OI Deasy, Joseph/0000-0002-9437-266X NR 66 TC 32 Z9 33 U1 0 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 MAR PY 2012 VL 39 IS 3 BP 1386 EP 1409 DI 10.1118/1.3685447 PG 24 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 908PV UT WOS:000301503400026 ER PT J AU Weinstein, MM AF Weinstein, Milena M. TI Hormone therapy and urinary incontinence SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID PROGESTIN; ESTROGEN; RISK C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weinstein, MM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAR PY 2012 VL 19 IS 3 BP 255 EP 256 DI 10.1097/gme.0b013e31824e9bb0 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 899ZA UT WOS:000300854000004 PM 22367730 ER PT J AU Sreenivasan, R Bassett, EK Cervantes, TM Hoganson, DM Vacanti, JP Gleason, KK AF Sreenivasan, Ramaswamy Bassett, Erik K. Cervantes, Thomas M. Hoganson, David M. Vacanti, Joseph P. Gleason, Karen K. TI Solvent-free surface modification by initiated chemical vapor deposition to render plasma bonding capabilities to surfaces SO MICROFLUIDICS AND NANOFLUIDICS LA English DT Article DE iCVD; Plasma bonding; Solvent-free; Surface modification ID SYSTEMS AB A versatile solvent-free method for surface modification of various materials including both metals and polymers is described. Strong irreversible bonds were formed when substrates modified by initiated chemical vapor deposition (iCVD) of poly(1,3,5-trivinyltrimethylcyclotrisiloxane) or poly(V3D3) and exposed to an oxygen plasma were brought into contact with plasma-treated poly(dimethylsiloxane) (PDMS). The strength of these bonds was quantified by burst pressure testing microfluidic channels in the PDMS. The burst pressures of PDMS bonded to various coated substrates were in some cases comparable to that of PDMS bonded directly to PDMS. In addition, porous PTFE membrane coated with poly(V3D3) was successfully bonded to a PDMS microfluidic device and withstood pressures of over 300 mmHg. Bond strength was shown to correlate with surface roughness and quality of the bond between the coating and substrate. This work paves a methodology to fabricate microfluidic devices that include a specifically tailored membrane. Furthermore, the bonded devices exhibited hydrolytic stability; no dramatic change was observed even after immersion in water at room temperature over a period of 10 days. C1 [Sreenivasan, Ramaswamy; Gleason, Karen K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Bassett, Erik K.; Cervantes, Thomas M.; Hoganson, David M.; Vacanti, Joseph P.] Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. RP Gleason, KK (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM kkg@mit.edu RI Gleason, Karen/G-1471-2013 OI Gleason, Karen/0000-0001-6127-1056 FU US Army through the Institute for Soldier Nanotechnologies [DAAD-19-02-D-0002]; US Army Research Office FX This research was supported in part by the US Army through the Institute for Soldier Nanotechnologies, under Contract DAAD-19-02-D-0002 with the US Army Research Office. NR 13 TC 3 Z9 3 U1 1 U2 22 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1613-4982 EI 1613-4990 J9 MICROFLUID NANOFLUID JI Microfluid. Nanofluid. PD MAR PY 2012 VL 12 IS 5 BP 835 EP 839 DI 10.1007/s10404-011-0913-3 PG 5 WC Nanoscience & Nanotechnology; Instruments & Instrumentation; Physics, Fluids & Plasmas SC Science & Technology - Other Topics; Instruments & Instrumentation; Physics GA 897QU UT WOS:000300670200017 ER PT J AU Litvan, I Goldman, JG Troster, AI Schmand, BA Weintraub, D Petersen, RC Mollenhauer, B Adler, CH Marder, K Williams-Gray, CH Aarsland, D Kulisevsky, J Rodriguez-Oroz, MC Burn, DJ Barker, RA Emre, M AF Litvan, Irene Goldman, Jennifer G. Troester, Alexander I. Schmand, Ben A. Weintraub, Daniel Petersen, Ronald C. Mollenhauer, Brit Adler, Charles H. Marder, Karen Williams-Gray, Caroline H. Aarsland, Dag Kulisevsky, Jaime Rodriguez-Oroz, Maria C. Burn, David J. Barker, Roger A. Emre, Murat TI Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; cognition; mild cognitive impairment; diagnostic criteria; dementia ID SLEEP BEHAVIOR DISORDER; DEMENTIA RATING-SCALE; CSF AMYLOID-BETA; NEUROPSYCHOLOGICAL CHARACTERISTICS; DECLINE; COHORT; MOCA; MULTICENTER; BIOMARKERS; CAMPAIGN AB Mild cognitive impairment is common in nondemented Parkinson's disease (PD) patients and may be a harbinger of dementia. In view of its importance, the Movement Disorder Society commissioned a task force to delineate diagnostic criteria for mild cognitive impairment in PD. The proposed diagnostic criteria are based on a literature review and expert consensus. This article provides guidelines to characterize the clinical syndrome and methods for its diagnosis. The criteria will require validation, and possibly refinement, as additional research improves our understanding of the epidemiology, presentation, neurobiology, assessment, and long-term course of this clinical syndrome. These diagnostic criteria will support future research efforts to identify at the earliest stage those PD patients at increased risk of progressive cognitive decline and dementia who may benefit from clinical interventions at a predementia stage. (c) 2012 Movement Disorder Society C1 [Litvan, Irene] Univ Louisville, Dept Neurol, Div Movement Disorders, Louisville, KY 40292 USA. [Litvan, Irene] Frazier Rehab Neurosci Inst, Movement Disorders Program, Louisville, KY USA. [Goldman, Jennifer G.] Rush Univ, Med Ctr, Sect Parkinson Dis & Movement Disorders, Dept Neurol Sci, Chicago, IL 60612 USA. [Troester, Alexander I.] Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA. [Schmand, Ben A.] Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands. [Schmand, Ben A.] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands. [Weintraub, Daniel] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Ctr, Philadelphia, PA USA. [Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. [Petersen, Ronald C.] Mayo Clin, Mayo Alzheimers Dis Res Ctr, Rochester, MN USA. [Mollenhauer, Brit] Univ Gottingen, Gottingen, Germany. [Mollenhauer, Brit] Paracelsus Elena Klin, Kassel, Germany. [Adler, Charles H.] Mayo Clin, Dept Neurol, Parkinsons Dis & Movement Disorders Ctr, Scottsdale, AZ USA. [Marder, Karen] Columbia Univ, Dept Neurol, New York Presbyterian Hosp, Taub Inst Alzheimers Dis & Aging Brain,Med Ctr, New York, NY USA. [Williams-Gray, Caroline H.; Barker, Roger A.] Univ Cambridge, Dept Clin Neurosci, Cambridge Ctr Brain Repair, Cambridge, England. [Aarsland, Dag] Karolinska Inst, Stockholm, Sweden. [Aarsland, Dag] Stavanger Univ Hosp, Ctr Age Related Med, Stavanger, Norway. [Aarsland, Dag] Univ Oslo, Akershus Univ Hosp, Oslo, Norway. [Kulisevsky, Jaime] Univ Autonoma Barcelona, St Pau Hosp, Dept Neurol, Movement Disorders Unit, E-08193 Barcelona, Spain. [Kulisevsky, Jaime] Univ Autonoma Barcelona, Inst Biomed Res IIB St Pau, E-08193 Barcelona, Spain. [Kulisevsky, Jaime; Rodriguez-Oroz, Maria C.] Ctr Invest Biomed Red Enfermedad Neurodegenerat, Barcelona, Spain. [Rodriguez-Oroz, Maria C.] Hosp Donostia, Dept Neurol, Donostia San Sebastian, Spain. [Rodriguez-Oroz, Maria C.] BioDonostia Res Inst, Neurosci Unit, San Sebatian, Spain. [Rodriguez-Oroz, Maria C.] Basque Fdn Sci, Ikerbasque, Bilbao, Spain. [Burn, David J.] Newcastle Univ, Inst Hlth & Aging, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Emre, Murat] Istanbul Univ, Istanbul Fac Med, Dept Neurol, Behav Neurol & Movement Disorders Unit, Istanbul, Turkey. RP Litvan, I (reprint author), Univ Calif San Diego, Movement Disorder Program, Dept Neurosci, 8950 Villa La Jolla Dr,Suite C112, La Jolla, CA 92037 USA. EM ilitvan@ucsd.edu OI Aarsland, Dag/0000-0001-6314-216X FU Medtronic; GlaxoSmithKline; National Parkinson Foundation; National Institutes of Health [P50 AG016574, U01 AG006786, NS36630, RR024156]; Parkinson's UK; European Union; Child Health and Development Institute; Michael J. Fox Foundation for Parkinson's Research; Teva Lundbeck; Springer FX A.I. T. has held consultancies with Medtronic, St. Jude Medical, and Boston Scientific, has served on the advisory board of St. Jude Medical, has received honoraria from Medtronic and the Parkinson's Disease Foundation, and has been awarded grants from Medtronic, GlaxoSmithKline, and the National Parkinson Foundation; D. W. has served on the advisory board of Teva Pharmaceuticals and has received honoraria from The Michael J. Fox Foundation for Parkinson's Research; R. P. has held consultancies with GE Healthcare and Elan Pharmaceuticals, has served on the advisory boards of Pfizer and Janssen Alzheimer Immunotherapy, has been awarded grants from the National Institutes of Health (P50 AG016574 and U01 AG006786), and has received royalties from Oxford University Press; C. H. A. has held consultancies with Merck Serono and Teva Pharmaceuticals; K. M. has been awarded grants from the National Institutes of Health (NS36630 and RR024156); D. B. has received honoraria from Merck Serono and The Michael J. Fox Foundation for Parkinson's Research and has received royalties from Henry Stewart Talks; R. B. has held consultancies with Oxford Biomedica, has served on the advisory board of Teva Lundbeck, has received honoraria from GlaxoSmithKline, has been awarded grants from Parkinson's UK, the European Union FP7 program, the Child Health and Development Institute, and The Michael J. Fox Foundation for Parkinson's Research, has been employed by the University of Cambridge, has received royalties from Wiley and Cambridge University Press, and has received monetary compensation from Springer for editorial work for the Journal of Neurology; and M. E. has held a consultancy with Merck Serono, has served on the advisory board of Merck Serono, has received honoraria from Merck Serono, and has received a clinical study grant from Teva Lundbeck. Full financial disclosures and author roles may be found in the online version of this article. NR 61 TC 415 Z9 428 U1 16 U2 86 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 EI 1531-8257 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2012 VL 27 IS 3 BP 349 EP 356 DI 10.1002/mds.24893 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 906IS UT WOS:000301339300006 PM 22275317 ER PT J AU Xu, S Williams, ME Pavlakis, M Breu, AC AF Xu, Shuai Williams, Mark E. Pavlakis, Martha Breu, Anthony C. TI The UNOS 'preferential allocation' concept proposal for the allocation of deceased donor kidney transplants: implications for patients with diabetes SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Editorial Material DE allocation; deceased donor; diabetes; kidney transplantation; UNOS ID UNITED-STATES; RENAL-TRANSPLANTATION; DISPARITIES; RECIPIENTS; MORTALITY; DONATION; RISK; CARE C1 [Breu, Anthony C.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Xu, Shuai] Harvard Univ, Sch Med, Boston, MA USA. [Williams, Mark E.; Pavlakis, Martha] Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA. [Williams, Mark E.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Breu, AC (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. EM abreu@bidmc.harvard.edu NR 17 TC 2 Z9 2 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAR PY 2012 VL 27 IS 3 BP 869 EP 871 DI 10.1093/ndt/gfr768 PG 3 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 913WD UT WOS:000301907200002 PM 22287657 ER PT J AU Growdon, AS Camargo, CA Clark, S Hannon, M Mansbach, JM AF Growdon, Amanda S. Camargo, Carlos A., Jr. Clark, Sunday Hannon, Megan Mansbach, Jonathan M. TI Serum 25-Hydroxyvitamin D Levels Among Boston Trainee Doctors in Winter SO NUTRIENTS LA English DT Article DE vitamin D; deficiency; residents; indoor workers ID VITAMIN-D DEFICIENCY; D INSUFFICIENCY; HEALTH; PREVENTION; PREVALENCE AB As indoor workers, trainee doctors may be at risk for inadequate vitamin D. All trainee doctors (residents) in a Boston pediatric training program (residency) were invited to complete a survey, and undergo testing for serum 25-hydroxyvitamin D [ 25(OH) D], PTH, and calcium during a 3-week period in March 2010. We examined the association between resident characteristics and serum 25(OH) D using Chi2 and Kruskal-Wallis test and multivariable linear and logistic regression. Of the 119 residents, 102 (86%) participated. Although the mean serum 25(OH) D level was 67 nmol/L (+/- 26), 25 (25%) had a level <50 nmol/L and 3 (3%) residents had levels <25 nmol/L. In the multivariable model, factors associated with 25(OH) D levels were: female sex (beta 12.7, 95% CI 3.6, 21.7), white race (beta 21.7, 95% CI 11.7, 31.7), travel to more equatorial latitudes during the past 3 months (beta 6.3, 95% CI 2.0, 10.5) and higher daily intake of vitamin D (beta 1.1, 95% CI 0.04, 2.1). Although one in four residents in our study had a serum 25(OH) D <50 nmol/L, all of them would have been missed using current Centers for Medicare and Medicaid Services (CMS) screening guidelines. The use of traditional risk factors appears insufficient to identify low vitamin D in indoor workers at northern latitudes. C1 [Growdon, Amanda S.; Hannon, Megan; Mansbach, Jonathan M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Clark, Sunday] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. RP Growdon, AS (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med, 300 Longwood AvCe, Boston, MA 02115 USA. EM Amanda.Growdon@childrens.harvard.edu; ccamargo@partners.org; Sunday.Clark@gmail.com; Megan.Hannon@childrens.harvard.edu; Jonathan.Mansbach@childrens.harvard.edu FU Clinical Translational Science Award [UL1RR025758]; Children's Hospital Boston from the National Center for Research Resources; National Institutes of Health (Bethesda, MD) [K23 AI-77801]; MGH Center for D-receptor Activation Research (Boston, MA) FX The project described was supported by Clinical Translational Science Award UL1RR025758 to Harvard University and Children's Hospital Boston from the National Center for Research Resources as well as K23 AI-77801 from the National Institutes of Health (Bethesda, MD). 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. Carlos A. Camargo was supported, in part, by the MGH Center for D-receptor Activation Research (Boston, MA). NR 25 TC 5 Z9 5 U1 0 U2 0 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD MAR PY 2012 VL 4 IS 3 BP 197 EP 207 DI 10.3390/nu4030197 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 916RP UT WOS:000302121200004 PM 22666546 ER PT J AU Perry, LJP Jakobiec, FA Zakka, FR AF Perry, Lynn J. Poole Jakobiec, Frederick A. Zakka, Fouad R. TI Bacterial and Mucopeptide Concretions of the Lacrimal Drainage System: An Analysis of 30 Cases SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID TFF PEPTIDES; CHRONIC DACRYOCYSTITIS; NASOLACRIMAL DUCT; DACRYOLITHS; CANALICULITIS; SAC; ACTINOMYCOSIS; MUCINS; CALCULI AB Purpose: To demonstrate the histopathologic characteristics of different types of lacrimal drainage system concretions with clinical correlations. Methods: Thirty lacrimal drainage system concretions submitted to the Cogan Eye Pathology Laboratory at the Massachusetts Eye and Ear Infirmary over a 2-year period were reviewed. Concretions were studied in detail using their histopathologic staining features as revealed with hematoxylin and eosin, Gomori methenamine silver, periodic acid-Schiff, iron stain, and Brown-Hopps tissue gram stain. A separate retrospective chart review was conducted for each patient to identify any clinical correlations. Results: Two major forms of concretions were identified histopathologically: mucopeptide (7) and bacterial (20). Mucopeptide concretions were found exclusively within the lacrimal sac, while bacterial concretions were found chiefly in the canaliculus. A third category of "mixed" concretions with substantial mucopeptide and bacterial characteristics comprised 3 specimens. Bacterial concretions consisted of large matted masses of filamentous, presumed Actinomyces organisms that were easily identified with the Grocott's methenamine silver stain; they were frequently cocolonized at their edges with coccal bacterial forms. Mucopeptide concretions were generally devoid of cellular elements and were composed of broad bland whorls of diffusely eosinophilic, acellular, periodic acid-Schiff-positive material punctuated by lacunae. They were often cocolonized by small numbers of bacterial cocci and occasional fungi. Culture results disclosed low virulence species. All 3 types of concretions predominated in women. Patients with bacterial concretions frequently had dry eye symptoms. Conclusions: The 2 major types of lacrimal system concretions differ in their primary location and histopathologic composition. Further characterization may lead to an understanding of the mechanisms for their formation. Mucopeptide concretion is more appropriate than terms such as "dacryolith" and "mucolith," and bacterial concretion is a more appropriate term than "canaliculith," because of the absence of significant calcium or stone-like density in these masses. (Ophthal Plast Reconstr Surg 2012; 28: 126-133) C1 [Perry, Lynn J. Poole; Jakobiec, Frederick A.; Zakka, Fouad R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Perry, Lynn J. Poole; Jakobiec, Frederick A.; Zakka, Fouad R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cogan Eye Pathol Lab, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Suite 321,243 Charles St, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu FU Heed Ophthalmic Foundation, Cleveland Ohio FX Supported, in part, by a fellowship from the Heed Ophthalmic Foundation, Cleveland Ohio. This study is part of an Institutional Review Board-approved project. NR 41 TC 4 Z9 5 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR-APR PY 2012 VL 28 IS 2 BP 126 EP 133 DI 10.1097/IOP.0b013e31824c88a6 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 914SZ UT WOS:000301974000021 PM 22410660 ER PT J AU Chen, RWS Jakobiec, FA Zakka, FR Kazim, M AF Chen, Royce W. S. Jakobiec, Frederick A. Zakka, Fouad R. Kazim, Michael TI Orbital Perineurioma in the Setting of Dacryocystitis SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SOFT-TISSUE PERINEURIOMA; INTRANEURAL PERINEURIOMA; NERVE; IDENTIFICATION; TUMOR AB A benign orbital perineurioma was discovered just posterior to the lacrimal sac during surgery for recurrent bacterial dacryocystitis in an 83-year-old woman. The tumor was circumscribed but nonencapsulated and located exterior to the lacrimal sac mucosa. It was composed of cytologically bland spindle cells organized in graceful, elongated, and twisted bundles reminiscent of a storiform pattern. Immunohistochemical staining displayed a diagnostic pattern of Claudin-1, GLUT-1, and epithelial membrane antigen positivity. Malignant transformation is virtually unknown, even with incomplete excision. The differential diagnosis includes neurofibroma, schwannoma, leiomyoma, solitary fibrous tumor (CD34 positive), and low-grade fibromyxoid sarcoma. C1 [Jakobiec, Frederick A.; Zakka, Fouad R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Zakka, Fouad R.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Royce W. S.; Kazim, Michael] Columbia Univ Coll Phys & Surg, Div Ophthalm Plast & Reconstruct Surg, Dept Ophthalmol, Edward S Harkness Eye Inst, New York, NY 10032 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, 243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 17 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR-APR PY 2012 VL 28 IS 2 BP E51 EP E55 DI 10.1097/IOP.0b013e31822113c6 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 914SZ UT WOS:000301974000013 PM 21697758 ER PT J AU Karp, JF Rollman, BL Reynolds, CF Morse, JQ Lotrich, F Mazumdar, S Morone, N Weiner, DK AF Karp, Jordan F. Rollman, Bruce L. Reynolds, Charles F., III Morse, Jennifer Q. Lotrich, Frank Mazumdar, Sati Morone, Natalia Weiner, Debra K. TI Addressing Both Depression and Pain in Late Life: The Methodology of the ADAPT Study SO PAIN MEDICINE LA English DT Article DE Clinical Trial; Geriatrics; Depression; Back Pain; Survival Analysis ID LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIAL; PROBLEM-SOLVING THERAPY; PRIMARY-CARE PATIENTS; OLDER-ADULTS; MAJOR DEPRESSION; COLLABORATIVE CARE; CLINICAL-TRIALS; EXECUTIVE DYSFUNCTION; SUPPORTIVE THERAPY AB Objective. To describe the methodology of the first NIH-funded clinical trial for seniors with comorbid depression and chronic low back pain. Methods. Randomized controlled effectiveness trial using stepped care methodology. Participants are >= 60 years old. Phase 1 (6 weeks) is open treatment with venlafaxine xr 150 mg/day and supportive management (SM). Response is 2 weeks of PHQ-9 <= 5 and at least 30% improvement in the average numeric rating scale for pain. Nonresponders progress to phase 2 (14 weeks) in which they are randomized to high-dose venlafaxine xr (up to 300 mg/day) with problem solving therapy for depression and pain (PST-DP) or high-dose venlafaxine xr and continued SM. Primary outcomes are the univariate pain and depression response and both observed and self-reported disability. Survival analytic techniques will be used, and the clinical effect size will be estimated with the number needed to treat. We hypothesize that self-efficacy for pain management will mediate response for subjects randomized to venlafaxine xr and PST-DP. Results. Not applicable. Conclusions. The results of this trial will inform the care of these complex patients and further understanding of comorbid pain and depression in late life. C1 [Karp, Jordan F.; Rollman, Bruce L.; Reynolds, Charles F., III; Morse, Jennifer Q.; Lotrich, Frank; Mazumdar, Sati; Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15260 USA. [Rollman, Bruce L.; Morone, Natalia; Weiner, Debra K.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Mazumdar, Sati] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Karp, JF (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM karpjf@upmc.edu FU National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) [AG033575, KL2 RR024154]; NIH Roadmap for Medical Research FX Supported by grant AG033575 (Karp) and by grant KL2 RR024154 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The content is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. Medications were provided by Pfizer for this investigator initiated trial. NR 97 TC 6 Z9 6 U1 5 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD MAR PY 2012 VL 13 IS 3 BP 405 EP 418 DI 10.1111/j.1526-4637.2011.01322.x PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 909NV UT WOS:000301572300010 PM 22313547 ER PT J AU Li, PP Zhou, GY Zhu, XY Li, GL Yan, P Shen, LY Xu, Q Hamblin, MR AF Li, Pingping Zhou, Guoyu Zhu, Xinyuan Li, Guolin Yan, Peng Shen, Linyue Xu, Qin Hamblin, Michael R. TI Photodynamic therapy with hyperbranched poly(ether-ester) chlorin(e6) nanoparticles on human tongue carcinoma CAL-27 cells SO PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY LA English DT Article DE Photodynamic therapy (PDT); Chlorin(e6); Hyperbranched poly(ether-ester) (HPEE); Drug delivery system (DDS); Nanoparticles; Transmission electron microscopy ID DELIVERY; CANCER; TUMORS; PHTHALOCYANINE; POLYMERS AB Background: Hyperbranched polymers represent a new class of drug-delivery vehicle that can be used to prepare nanoparticles with uniform size distribution. Methods: In this study we prepared covalent conjugates between the photosensitizer chlorin(e6) and hyperbranched poly(ether-ester), HPEE. HPEE-ce6 nanoparticles were synthesized by carbodiimide-mediated reaction between HPEE and ce6, and characterized by ultraviolet-visible absorption spectroscopy (UV-Vis), and transmission electron microscopy (TEM). The uptake and phototoxicity of HPEE-ce6 nanoparticles towards human oral tongue cancer CAL-27 cells was detected by confocal laser scanning microscopy (CLSM) and MTT assay, respectively. Results: The absorption peak of HPEE-ce6 nanoparticles was red-shifted 12-nm compared with ce6, and TEM showed uniform nanoparticles with a diameter of 50-nm. HPEE-ce6 nanoparticles were taken up by CAL-27 cells after 4 h incubation and localized in the cytoplasm. The MTT assay showed a significantly (P < 0.05) higher phototoxicity compared to free ce6 after 12 J/cm(2) of 660-nm laser illumination. Conclusions: This is the first time to our knowledge that hyperbranched polymers have been used in PDT drug delivery. (c) 2011 Elsevier B.V. All rights reserved. C1 [Li, Pingping; Zhou, Guoyu; Shen, Linyue; Xu, Qin] Shanghai Jiao Tong Univ, Peoples Hosp Affiliated 9, Dept Oral Maxillofacial Surg,Coll Med, Shanghai Key Point Lab Stomatol,Sch Stomatol, Shanghai 200011, Peoples R China. [Li, Guolin] Haerbin Med Univ, Hosp Affiliated 1, Dept Oral Maxillofacial Surg, Haerbin 150001, Heilongjiang, Peoples R China. [Zhu, Xinyuan; Yan, Peng] Shanghai Jiao Tong Univ, Acad Chem, Shanghai 200240, Peoples R China. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Zhou, GY (reprint author), Shanghai Jiao Tong Univ, Peoples Hosp Affiliated 9, Dept Oral Maxillofacial Surg,Coll Med, Shanghai Key Point Lab Stomatol,Sch Stomatol, Shanghai 200011, Peoples R China. EM guoyuzhou@hotmail.com; xyzhu@sjtu.edu.cn OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research [FA9950-04-1-0079] FX The authors would like to thank Dr. Jian Sun at the Shanghai Jiaotong University for facilitating the collaboration. M.R. Hamblin was supported by NIH grant R01AI050875, Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514) and Air Force Office of Scientific Research (FA9950-04-1-0079). NR 29 TC 15 Z9 17 U1 3 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1572-1000 J9 PHOTODIAGN PHOTODYN JI Photodiagnosis Photodyn. Ther. PD MAR PY 2012 VL 9 IS 1 BP 76 EP 82 DI 10.1016/j.pdpdt.2011.08.001 PG 7 WC Oncology SC Oncology GA 914QB UT WOS:000301965300011 PM 22369732 ER PT J AU Turner, EH Knoepflmacher, D Shapley, L AF Turner, Erick H. Knoepflmacher, Daniel Shapley, Lee TI Publication Bias in Antipsychotic Trials: An Analysis of Efficacy Comparing the Published Literature to the US Food and Drug Administration Database SO PLOS MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; EXTENDED-RELEASE TABLETS; DOUBLE-BLIND; SCHIZOAFFECTIVE DISORDER; CLINICAL-TRIALS; ACUTE EXACERBATION; REPORTING BIAS; 2ND-GENERATION ANTIPSYCHOTICS; OLANZAPINE TRIAL; SCHIZOPHRENIA AB Background: Publication bias compromises the validity of evidence-based medicine, yet a growing body of research shows that this problem is widespread. Efficacy data from drug regulatory agencies, e. g., the US Food and Drug Administration (FDA), can serve as a benchmark or control against which data in journal articles can be checked. Thus one may determine whether publication bias is present and quantify the extent to which it inflates apparent drug efficacy. Methods and Findings: FDA Drug Approval Packages for eight second-generation antipsychotics-aripiprazole, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, risperidone long-acting injection (risperidone LAI), and ziprasidone-were used to identify a cohort of 24 FDA-registered premarketing trials. The results of these trials according to the FDA were compared with the results conveyed in corresponding journal articles. The relationship between study outcome and publication status was examined, and effect sizes derived from the two data sources were compared. Among the 24 FDA-registered trials, four (17%) were unpublished. Of these, three failed to show that the study drug had a statistical advantage over placebo, and one showed the study drug was statistically inferior to the active comparator. Among the 20 published trials, the five that were not positive, according to the FDA, showed some evidence of outcome reporting bias. However, the association between trial outcome and publication status did not reach statistical significance. Further, the apparent increase in the effect size point estimate due to publication bias was modest (8%) and not statistically significant. On the other hand, the effect size for unpublished trials (0.23, 95% confidence interval 0.07 to 0.39) was less than half that for the published trials (0.47, 95% confidence interval 0.40 to 0.54), a difference that was significant. Conclusions: The magnitude of publication bias found for antipsychotics was less than that found previously for antidepressants, possibly because antipsychotics demonstrate superiority to placebo more consistently. Without increased access to regulatory agency data, publication bias will continue to blur distinctions between effective and ineffective drugs. C1 [Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Turner, Erick H.] Oregon Hlth & Sci Univ, Dept Pharmacol, Portland, OR 97201 USA. [Turner, Erick H.] Oregon Hlth & Sci Univ, Ctr Eth Hlth Care, Portland, OR 97201 USA. [Turner, Erick H.] Portland VA Med Ctr, Behav Hlth & Neurosci Div, Portland, OR USA. [Knoepflmacher, Daniel; Shapley, Lee] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. RP Turner, EH (reprint author), Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. EM turnere@ohsu.edu FU Stanley Medical Research Institute [08D-1892]; Portland VA Research Foundation FX Grant support: Stanley Medical Research Institute, grant number 08D-1892 (http://www.stanleyresearch.org/dnn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Comments on methods: Stefan Leucht. Statistical input: David B. Wilson and Alex J. Sutton. Assistance with procurement of FDA and journal data: Julie Anderson. Administration of received grant funds: Portland VA Research Foundation. NR 67 TC 40 Z9 43 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAR PY 2012 VL 9 IS 3 AR e1001189 DI 10.1371/journal.pmed.1001189 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 916VY UT WOS:000302132500009 PM 22448149 ER PT J AU Alexander, SC Sullivan, AM Back, AL Tulsky, JA Goldman, RE Block, SD Stewart, SK Wilson-Genderson, M Lee, SJ AF Alexander, Stewart C. Sullivan, Amy M. Back, Anthony L. Tulsky, James A. Goldman, Roberta E. Block, Susan D. Stewart, Susan K. Wilson-Genderson, Maureen Lee, Stephanie J. TI Information giving and receiving in hematological malignancy consultations SO PSYCHO-ONCOLOGY LA English DT Article DE communication; physician-patient encounters; oncology; hematology; prognosis; cancer ID DOCTOR-PATIENT INTERACTION; INTENSIVE-CARE UNITS; COMMUNICATION-SKILLS; BAD-NEWS; PHYSICIAN COMMUNICATION; CONTROLLED-TRIAL; CANCER; ONCOLOGY; PROGNOSIS; OPPORTUNITIES AB Purpose: Little is known about communication with patients suffering from hematologic malignancies, many of whom are seen by subspecialists in consultation at tertiary-care centers. These subspecialized consultations might provide the best examples of optimal physicianpatient communication behaviors, given that these consultations tend to be lengthy, to occur between individuals who have not met before and may have no intention of an ongoing relationship, and which have a goal of providing treatment recommendations. The aim of this paper is to describe and quantify the content of the subspecialty consultation in regards to exchanging information and identify patient and provider characteristics associated with discussion elements. Methods: Audio-recorded consultations between 236 patients and 40 hematologists were coded for recommended communication practices. Multilevel models for dichotomous outcomes were created to test associations between patient, physician and consultation characteristics and key discussion elements. Results: Discussions about the purpose of the visit and patient's knowledge about their disease were common. Other elements such as patient's preference for his/ her role in decisionmaking, preferences for information, or understanding of presented information were less common. Treatment recommendations were provided in 97% of the consultations and unambiguous presentations of prognosis occurred in 81% of the consultations. Unambiguous presentations of prognosis were associated with non-White patient race, lower educational status, greater number of questions asked, and specific physician provider. Conclusion: Although some communication behaviors occur in most consultations, others are much less common and could help tailor the amount and type of information discussed. Approximately half of the patients are told unambiguous prognostic estimates for mortality or cure. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Alexander, Stewart C.; Tulsky, James A.] Duke Univ, Med Ctr, Ctr Palliat Care, Durham, NC 27705 USA. [Alexander, Stewart C.; Tulsky, James A.] Durham VA Med Ctr, Ctr Hlth Serv Res, Durham, NC USA. [Alexander, Stewart C.; Tulsky, James A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27705 USA. [Sullivan, Amy M.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Back, Anthony L.] Univ Washington, Dept Med, Washington, DC USA. [Goldman, Roberta E.] Brown Univ, Warren Alpert Med Sch, Dept Family Med, Providence, RI 02912 USA. [Goldman, Roberta E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Behav & Hlth, Ann Arbor, MI USA. [Block, Susan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Block, Susan D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Stewart, Susan K.] Blood & Marrow Transplant Informat Network, Duarte, CA USA. [Wilson-Genderson, Maureen] Virginia Commonwealth Univ, Dept Social & Behav Hlth, Richmond, VA USA. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Alexander, SC (reprint author), Duke Univ, Med Ctr, Ctr Palliat Care, Hock Plaza,Suite 1105,2424 Erwin Rd, Durham, NC 27705 USA. EM alexa045@mc.duke.edu FU National Cancer Institute [CA 098486]; Department of Veterans Affairs [RCD 07-006] FX The authors wish to thank all the physicians and patients who participated in this study, and the study project managers: Christina Caron, Arnold Gonzales, Tarrah Kirkpatrick, M. Shannon Hill, and Kate Chilson. This work was supported by CA 098486 from the National Cancer Institute. Designed research and drafted the manuscript (S. C. A., A. S., S. J. L.), performed the statistical analysis (A. S., M. W. G.), interpreted data and critically revised the manuscript (S. C. A., A. S., A. L. B., J. A. T., R. E. G., S. B., S. K. S., S. J. L.). Dr. Alexander was supported by Health Services Research Career Development Award RCD 07-006 from the Department of Veterans Affairs. The authors have no conflicts of interest to declare. NR 45 TC 10 Z9 10 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD MAR PY 2012 VL 21 IS 3 BP 297 EP 306 DI 10.1002/pon.1891 PG 10 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 901SP UT WOS:000300987400009 PM 21294221 ER PT J AU Rosenthal, D Callstrom, MR AF Rosenthal, Daniel Callstrom, Matthew R. TI Critical Review and State of the Art in Interventional Oncology: Benign and Metastatic Disease Involving Bone SO RADIOLOGY LA English DT Review ID PERCUTANEOUS RADIOFREQUENCY ABLATION; FOCUSED ULTRASOUND SURGERY; IMAGE-GUIDED ABLATION; OSTEOID-OSTEOMA; THERMAL ABLATION; RANDOMIZED-TRIAL; EX-VIVO; UNUSUAL COMPLICATION; OPERATIVE TREATMENT; OSSEOUS METASTASES AB Image-guided percutaneous ablation methods have proved effective for treatment of benign bone tumors and for palliation of metastases involving bone and soft-tissue sites beyond the liver and lung. Image-guided radiofrequency ablation is now the standard treatment for osteoid osteoma, as the procedure can be performed with higher rates of technical success, decreased morbidity, and lower cost than those obtained with open surgery. Several ablation methods have been used to effectively palliate focal painful metastatic disease involving bone and soft-tissue sites beyond the liver and lung. Substantial pain reduction is possible in patients who have failed to achieve benefit from conventional therapies, including chemotherapy and external-beam radiation. Importantly, the pain reduction that is achieved is durable over many months of observation. C1 [Callstrom, Matthew R.] Mayo Clin, Dept Radiol, Rochester, MN 55905 USA. [Rosenthal, Daniel] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Callstrom, MR (reprint author), Mayo Clin, Dept Radiol, 200 1st St SW, Rochester, MN 55905 USA. EM callstrom.matthew@mayo.edu FU Siemens Medical and Endocare FX D.R. No potential conflicts of interest to disclose. M. R. C. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: institution received research grants from Siemens Medical and Endocare. Other relationships: none to disclose. NR 106 TC 52 Z9 52 U1 0 U2 6 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 MAR PY 2012 VL 262 IS 3 BP 765 EP 780 DI 10.1148/radiol.11101384 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 916RR UT WOS:000302121400005 PM 22357881 ER PT J AU Kong, CY Lee, JM McMahon, PM Lowry, KP Omer, ZB Eisenberg, JD Pandharipande, PV Gazelle, GS AF Kong, Chung Y. Lee, Janie M. McMahon, Pamela M. Lowry, Kathryn P. Omer, Zehra B. Eisenberg, Jonathan D. Pandharipande, Pari V. Gazelle, G. Scott TI Using Radiation Risk Models in Cancer Screening Simulations: Important Assumptions and Effects on Outcome Projections SO RADIOLOGY LA English DT Article ID EARLY LUNG-CANCER; BREAST-CANCER; MUTATION CARRIERS; COMPUTED-TOMOGRAPHY; COST-EFFECTIVENESS; FILM MAMMOGRAPHY; CT; BRCA1; MORTALITY; RADIOLOGY AB Purpose: To evaluate the effect of incorporating radiation risk into microsimulation (first-order Monte Carlo) models for breast and lung cancer screening to illustrate effects of including radiation risk on patient outcome projections. Materials and Methods: All data used in this study were derived from publicly available or deidentified human subject data. Institutional review board approval was not required. The challenges of incorporating radiation risk into simulation models are illustrated with two cancer screening models (Breast Cancer Model and Lung Cancer Policy Model) adapted to include radiation exposure effects from mammography and chest computed tomography (CT), respectively. The primary outcome projected by the breast model was life expectancy (LE) for BRCA1 mutation carriers. Digital mammographic screening beginning at ages 25, 30, 35, and 40 years was evaluated in the context of screenings with false-positive results and radiation exposure effects. The primary outcome of the lung model was lung cancer-specific mortality reduction due to annual screening, comparing two diagnostic CT protocols for lung nodule evaluation. The Metropolis-Hastings algorithm was used to estimate the mean values of the results with 95% uncertainty intervals (UIs). Results: Without radiation exposure effects, the breast model indicated that annual digital mammography starting at age 25 years maximized LE (72.03 years; 95% UI: 72.01 years, 72.05 years) and had the highest number of screenings with false-positive results (2.0 per woman). When radiation effects were included, annual digital mammography beginning at age 30 years maximized LE (71.90 years; 95% UI: 71.87 years, 71.94 years) with a lower number of screenings with false-positive results (1.4 per woman). For annual chest CT screening of 50-year-old females with no follow-up for nodules smaller than 4 mm in diameter, the lung model predicted lung cancer-specific mortality reduction of 21.50% (95% UI: 20.90%, 22.10%) without radiation risk and 17.75% (95% UI: 16.97%, 18.41%) with radiation risk. Conclusion: Because including radiation exposure risk can influence long-term projections from simulation models, it is important to include these risks when conducting modeling-based assessments of diagnostic imaging. (C) RSNA, 2012 C1 [Kong, Chung Y.; Lee, Janie M.; McMahon, Pamela M.; Lowry, Kathryn P.; Omer, Zehra B.; Eisenberg, Jonathan D.; Pandharipande, Pari V.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Kong, Chung Y.; Lee, Janie M.; McMahon, Pamela M.; Lowry, Kathryn P.; Pandharipande, Pari V.; Gazelle, G. Scott] Harvard Univ, Sch Med, Boston, MA USA. [Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Kong, CY (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM joey@mgh-ita.org FU National Institutes of Health [K25CA133141, K07CA128816, R00CA126147, NIHK07133097]; National Cancer Institute; National Cancer Institute [R00 CA 126147, R01 CA 97337, U01CA152956]; American Cancer Society [2008A060554] FX This research was supported by the National Institutes of Health (grants K25CA133141, K07CA128816, and R00CA126147).; Financial activities related to the present article: institution received a grant from the National Cancer Institute.; Financial activities related to the present article: institution received grant R00 CA 126147, R01 CA 97337 from the National Cancer Institute and grant 2008A060554 from the American Cancer Society.; Financial activities not related to the present article: institution received grant U01CA152956 from the National Cancer Institute.; Financial activities related to the present article: institution received Career Development Award NIHK07133097 from the National Institutes of Health. NR 33 TC 11 Z9 11 U1 0 U2 3 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 MAR PY 2012 VL 262 IS 3 BP 977 EP 984 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 916RR UT WOS:000302121400027 PM 22357897 ER PT J AU Aristophanous, M Yong, Y Yap, JT Killoran, JH Allen, AM Berbeco, RI Chen, AB AF Aristophanous, Michalis Yong, Yue Yap, Jeffrey T. Killoran, Joseph H. Allen, Aaron M. Berbeco, Ross I. Chen, Aileen B. TI Evaluating FDG uptake changes between pre and post therapy respiratory gated PET scans SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE 4D PET/CT; Therapy response; Biological target volume; Lung cancer ID POSITRON-EMISSION-TOMOGRAPHY; CELL LUNG-CANCER; F-18-FDG PET; SOLID TUMORS; IMAGES; LESIONS; CT; RECOMMENDATIONS; RADIOTHERAPY; CRITERIA AB Purpose: Whole body (3D) and respiratory gated (4D) FDG-PET/CT scans performed pre-radiotherapy (pre-RT) and post-radiotherapy (post-RT) were analyzed to investigate the impact of 4D PET in evaluating 18F-fluorodeoxyglucose (FDG) uptake changes due to therapy, relative to traditional 3D PET. Methods and materials: 3D and 4D sequential FDG-PET/CT scans were acquired pre-RT and approximately one month post-RT for patients with non-small cell lung cancer (NSCLC). The lesions of high uptake targeted with radiotherapy were identified on the pre-RT scan of each patient. Each lesion on the 3D and each of the five phases of the 4D scan were analyzed using a region of interest (ROI). For each patient the ROIs of the pre-RT scans were used to locate the areas of initial FDG uptake on the post-RT scans following rigid registration. Post-RT ROIs were drawn and the FDG uptake was compared with that of the pre-RT scans. Results: Sixteen distinct lesions from 12 patients were identified and analyzed. Standardized uptake value (SUV) maxima were significantly higher (p-value <0.005) for the lesions as measured on the 4D compared to 3D PET. Comparison of serial pre and post-RT scans showed a mean 62% decrease in SUV with the 3D PET scan (range 36-89%), and a 67% decrease with the 4D PET scan (range 30-89%). The mean absolute difference in SUV change on 3D versus 4D scans was 4.9%, with a range 0-15% (p-value = 0.07). Conclusions: Signal recovery with 4D PET results in higher SUVs when compared to standard 3D PET. Consequently, differences in the evaluation of SUV changes between pre and post-RT plans were observed. Such difference can have a significant impact in PET-based response assessment. (c) 2012 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 102 (2012) 377-382 C1 [Aristophanous, Michalis; Yong, Yue; Killoran, Joseph H.; Allen, Aaron M.; Berbeco, Ross I.; Chen, Aileen B.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Yap, Jeffrey T.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiol, Boston, MA USA. [Yap, Jeffrey T.] Harvard Univ, Sch Med, Boston, MA USA. RP Aristophanous, M (reprint author), UT MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX USA. EM maristophanous@mdanderson.org OI Chen, Aileen/0000-0002-5385-3360 NR 26 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAR PY 2012 VL 102 IS 3 BP 377 EP 382 DI 10.1016/j.radonc.2011.12.015 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 915SY UT WOS:000302048900009 PM 22265731 ER PT J AU Pan, CS Huo, YQ An, XJ Singh, G Chen, M Yang, ZX Pu, JX Li, J AF Pan, Chunshui Huo, Yingqing An, Xiaojin Singh, Gurbakhshish Chen, Meng Yang, Zhaoxiang Pu, Junxue Li, Jian TI Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation SO VASCULAR PHARMACOLOGY LA English DT Article DE Panax notoginseng (PN); Rb1; Rg1; Hypertension; Vasodilatation ID PERFORMANCE LIQUID-CHROMATOGRAPHY; NITRIC-OXIDE PRODUCTION; RED GINSENG; SIGNALING PATHWAY; ACTIVE SAPONINS; RAT AORTA; CELLS; GINSENOSIDES; INCREASES; CONTRACTION AB Ginsenoside Rb1 and Rg1 are major components of Panax notoginseng (P.N.), an herb with known clinical efficacy in hypertension and myocardial ischemia in Eastern countries. This investigation is to elicit the mechanism of these components in hypertension via their effect on vascular reaction. To assess the ability of P.N. in hypertension, P.N. extracts were injected in spontaneously hypertensive rats (SHR) via the vena caudalis; Low dosages of P.N. extracts significantly lowered blood pressure in SHR. Examination with Rb1 and Rg1 revealed significant vasodilatation using mouse coronary arteries in a dose-dependent manner. Rb1- and Rg1-induced vasodilatation was blocked by pre-incubation with eNOS and PI3K inhibitors. Coronaries of eNOS-/- mice showed attenuated vasodilatation with Rb1 and Rg1. In addition, both Rb1 and Rg1 induce nitric oxide (NO) generation through increasing the phosphorylation of eNOS, activating Na+ -independent L-arginine transport, and stimulating cationic amino acid transport (CAT)-1 mRNA expression in cultured endothelial cells. Conclusion: Ginsenoside Rb1 and Rg1 increased endothelial-dependent vessel dilatation through the activation of NO by modulating the PI3K/Akt/eNOS pathway and L-arginine transport in endothelial cells. These findings may have important implications for understanding the mechanisms of clinical efficacy of the herb P.N. when used in the regulation of blood pressure. (C) 2011 Elsevier Inc. All rights reserved. C1 [An, Xiaojin; Singh, Gurbakhshish; Li, Jian] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med,CardioVasc Inst, Boston, MA 02115 USA. [Pan, Chunshui; Huo, Yingqing; An, Xiaojin; Chen, Meng; Li, Jian] Peking Univ, Inst Mol Med, Lab Vasc Biol, Beijing 100871, Peoples R China. [Yang, Zhaoxiang; Pu, Junxue] Kunming Pharmaceut Inst, Kunming, Yunnan, Peoples R China. RP Li, J (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc Med,CardioVasc Inst, 3 Blackfan Circle, Boston, MA 02115 USA. EM JLi@BIDMC.Harvard.edu FU National Natural Science Foundation of China [NNSFC-30672740]; Kunming Pharmaceutical Institute, Yunnan, China; NIH [NIH R21HL088219, HLR01082837] FX This work was supported by the National Natural Science Foundation of China NNSFC-30672740 (Li), the Kunming Pharmaceutical Institute, Yunnan, China (Pu and Yang), NIH grants NIH R21HL088219 and HLR01082837 (Li). We thank Ms. Brittany L. Cully and Ms. Melissa Philbrick for editing the manuscript. NR 37 TC 32 Z9 38 U1 1 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1537-1891 J9 VASC PHARMACOL JI Vasc. Pharmacol. PD MAR-APR PY 2012 VL 56 IS 3-4 BP 150 EP 158 DI 10.1016/j.vph.2011.12.006 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 917TM UT WOS:000302201500006 PM 22239978 ER PT J AU Cardoza, JD Parikh, JR Ficarro, SB Marto, JA AF Cardoza, Job D. Parikh, Jignesh R. Ficarro, Scott B. Marto, Jarrod A. TI Mass spectrometry-based proteomics: qualitative identification to activity-based protein profiling SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE LA English DT Review ID ELECTRON-TRANSFER DISSOCIATION; CODED AFFINITY TAGS; HYDROPHILIC INTERACTION CHROMATOGRAPHY; COLLISION-INDUCED DISSOCIATION; ENZYME-ACTIVITY PROFILES; EMBRYONIC STEM-CELLS; FREE CLICK CHEMISTRY; LINEAR ION-TRAP; TYROSINE PHOSPHORYLATION; PHOSPHOPROTEOME ANALYSIS AB Mass spectrometry has become the method of choice for proteome characterization, including multicomponent protein complexes (typically tens to hundreds of proteins) and total protein expression (up to tens of thousands of proteins), in biological samples. Qualitative sequence assignment based on MS/MS spectra is relatively well-defined, while statistical metrics for relative quantification have not completely stabilized. Nonetheless, proteomics studies have progressed to the point whereby various gene-, pathway-, or network-oriented computational frameworks may be used to place mass spectrometry data into biological context. Despite this progress, the dynamic range of protein expression remains a significant hurdle, and impedes comprehensive proteome analysis. Methods designed to enrich specific protein classes have emerged as an effective means to characterize enzymes or other catalytically active proteins that are otherwise difficult to detect in typical discovery mode proteomics experiments. Collectively, these approaches will facilitate identification of biomarkers and pathways relevant to diagnosis and treatment of human disease. WIREs Syst Biol Med 2012, 4:141162. doi: 10.1002/wsbm.166 C1 [Cardoza, Job D.; Parikh, Jignesh R.; Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Cardoza, Job D.; Ficarro, Scott B.; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Parikh, Jignesh R.] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Ficarro, Scott B.; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Boston, MA 02115 USA. RP Marto, JA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM jarrod_marto@dfci.harvard.edu FU Dana-Farber Cancer Institute; National Institutes of Health, NHGRI [P50HG004233]; National Institutes of Health, NINDS [P01NS047572] FX Generous support for this work was provided by the Dana-Farber Cancer Institute and the National Institutes of Health, NHGRI (P50HG004233), and NINDS (P01NS047572). NR 175 TC 4 Z9 4 U1 1 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1939-5094 EI 1939-005X J9 WIRES SYST BIOL MED JI Wiley Interdiscip. Rev.-Syst. Biol PD MAR-APR PY 2012 VL 4 IS 2 BP 141 EP 162 DI 10.1002/wsbm.166 PG 22 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 896LZ UT WOS:000300569300002 PM 22231900 ER PT J AU Kelley, SD de Andrade, ARV Bickman, L Robin, AV AF Kelley, Susan Douglas de Andrade, Ana Regina Vides Bickman, Leonard Robin, Ashley V. TI The Session Report Form (SRF): Are Clinicians Addressing Concerns Reported by Youth and Caregivers? SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Youth; Caregiver; Clinician; Session Report Form; Treatment as usual; Describing practice; Respondent differences ID INFORMANT DISCREPANCIES; LOGISTIC-REGRESSION; MEASUREMENT ERROR; CHILD; THERAPY; PSYCHOTHERAPY; ASSESSMENTS; OUTCOMES; CLIENTS; SYSTEM AB This study explores the relationship between clinician-reported content addressed in sessions, measured with the Session Report Form (SRF), and multi-informant problem alerts stemming from a larger battery of treatment process and progress measures. Multilevel Multinomial Logit Models were conducted with 133 clinicians and 299 youths receiving home-based treatment (N = 3,143 sessions). Results indicate a strong relationship between session content and problems related to youth symptoms and functioning as reported by clinicians in the same session. Session content was related to emotional, family, and friend/peer problems reported by youth and youth behavioral problems reported by caregivers. High-risk problems (alcohol/substance use, harm to self or others) were strongly related to session content regardless of informant. Session content was not related to problem alerts associated with the treatment process, caregiver strain, or client/caregiver strengths. The SRF appears to be a useful measure for assessing common themes addressed in routine mental health settings. C1 [Kelley, Susan Douglas; de Andrade, Ana Regina Vides; Bickman, Leonard] Vanderbilt Univ, Peabody Coll 151, Ctr Evaluat & Program Improvement, Nashville, TN 37203 USA. [Robin, Ashley V.] US Dept Vet Affairs, Washington, DC 20420 USA. RP Kelley, SD (reprint author), Vanderbilt Univ, Peabody Coll 151, Ctr Evaluat & Program Improvement, 230 Appleton Pl, Nashville, TN 37203 USA. EM Susan.D.Kelley@vanderbilt.edu RI Price, Katie/H-1931-2012; OI Bickman, Leonard/0000-0002-0746-3791 FU NIMH NIH HHS [R01 MH087814, R01-MH4264600201, R01 MH068589-02, R01 MH068589, R01-MH068589] NR 39 TC 2 Z9 2 U1 1 U2 4 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD MAR PY 2012 VL 39 IS 1-2 SI SI BP 133 EP 145 DI 10.1007/s10488-012-0415-y PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 909WT UT WOS:000301597800013 PM 22407564 ER PT J AU Lee, C Klaustermeyer, WB AF Lee, C. Klaustermeyer, W. B. TI Effect of high dose inhaled corticosteroids on cell mediated immunity in patients with asthma SO ALLERGOLOGIA ET IMMUNOPATHOLOGIA LA English DT Article DE Asthma; Cell mediated immunity; Delayed type hypersensitivity skin test; Infection; Inhaled corticosteroids ID BONE-MINERAL DENSITY; FLUTICASONE PROPIONATE; PULMONARY TUBERCULOSIS; HOSPITALIZED-PATIENTS; CHILDREN; THERAPY; BECLOMETHASONE; BUDESONIDE; SUPPRESSION; VOLUNTEERS AB Background: Cell mediated immunity is suppressed by systemic corticosteroids. Inhaled corticosteroids have been shown to affect parameters including bone metabolism, hypothalamus-pituitary adrenal axis, linear growth, and lead to the development of cataracts. However, it is unclear if high dose inhaled corticosteroid therapy affects cell mediated immunity. Study objectives: To evaluate if asthma patients taking high dose inhaled corticosteroids chronically have reduced cell mediated immunity compared to asthma patients not taking inhaled corticosteroids. Methods: Eighteen asthmatic subjects participated in this cross-sectional study. Cell mediated immunity was evaluated in nine patients who had been taking high dose inhaled corticosteroids for >6 months and nine patients not taking inhaled corticosteroids. Cell mediated immunity was evaluated by delayed type hypersensitivity (DTH) skin testing with intradermal placement of candida and tetanus antigens. Results: There was no significant difference in DTH skin test results between the high dose inhaled corticosteroid and no corticosteroid treated asthma group. Conclusion: Patients with asthma taking high dose inhaled corticosteroids chronically (>6 months) did not have significantly greater impaired cell mediated immunity than patients not taking inhaled corticosteroids in this study. (c) 2011 SEICAP. Published by Elsevier Espana, S.L. All rights reserved. C1 [Lee, C.; Klaustermeyer, W. B.] Univ Calif Los Angeles, Dept Med, Div Allergy & Immunol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RP Lee, C (reprint author), Univ Calif Los Angeles, Dept Med, Div Allergy & Immunol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. EM christina.h.lee@hotmail.com NR 39 TC 2 Z9 3 U1 0 U2 1 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0301-0546 J9 ALLERGOL IMMUNOPATH JI Allergol. Immunopath. PD MAR-APR PY 2012 VL 40 IS 2 BP 100 EP 103 DI 10.1016/j.aller.2011.11.001 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 907DR UT WOS:000301398500007 PM 22236734 ER PT J AU Hoffmann, U Truong, QA Fleg, JL Goehler, A Gazelle, S Wiviott, S Lee, H Udelson, JE Schoenfeld, D AF Hoffmann, Udo Truong, Quynh A. Fleg, Jerome L. Goehler, Alexander Gazelle, Scott Wiviott, Stephen Lee, Hang Udelson, James E. Schoenfeld, David TI Design of the Rule Out Myocardial Ischemia/Infarction Using Computer Assisted Tomography: A multicenter randomized comparative effectiveness trial of cardiac computed tomography versus alternative triage strategies in patients with acute chest pain in the emergency department SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; TIMI RISK SCORE; CT ANGIOGRAPHY; ROMICAT TRIAL; PERFORMANCE; POPULATION; OUTCOMES AB Although early cardiac computed tomographic angiography (CCTA) might improve the management of emergency department (ED) patients with acute chest pain, it could also result in increased testing, costs, and radiation exposure. ROMICAT II was a randomized comparative effectiveness trial enrolling patients 40 to 74 years old without known coronary artery disease who presented to the ED with chest pain but without ischemic electrocardiographic (ECG) changes or elevated initial troponin and who required further risk stratification. Overall, 1000 patients at 9 sites within the United States were randomized to either CCTA as the first diagnostic test following serial biomarkers or to standard of care, which included no testing or functional testing such as exercise ECG, stress radionuclide imaging, or stress echocardiography. Test results were provided to ED physicians, yet patient management was not driven by a study protocol in either arm. Data were collected on diagnostic testing, cardiac events, and cost of medical care for the index hospitalization and during the following 28 days. The primary end point was length of hospital stay. Secondary end points were cumulative radiation exposure, resource utilization, and costs of competing strategies. Tertiary end points were institutional, physician, and patient characteristics associated with primary and secondary outcomes. Rate of missed acute coronary syndrome within 28 days was the safety end point. The ROMICAT II will provide rigorous data on whether CCTA is more efficient than standard of care in the management of patients with acute chest pain at intermediate risk for acute coronary syndrome. (Am Heart J 2012;163:330-338.e1.) C1 [Hoffmann, Udo; Truong, Quynh A.; Goehler, Alexander] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Hoffmann, Udo; Truong, Quynh A.; Goehler, Alexander; Gazelle, Scott; Wiviott, Stephen; Lee, Hang; Schoenfeld, David] Harvard Univ, Sch Med, Boston, MA USA. [Hoffmann, Udo; Truong, Quynh A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA. [Goehler, Alexander; Gazelle, Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Wiviott, Stephen] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Wiviott, Stephen] TIMI Study Grp, Boston, MA USA. [Wiviott, Stephen; Lee, Hang; Schoenfeld, David] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org RI Shapiro, Nathan/F-1718-2016 FU NHLBI [U01HL092040]; NIH [K23HL098370, L30HL093896] FX The study is funded by the NHLBI U01HL092040. Dr. Truong received support from NIH grants K23HL098370 and L30HL093896. NR 28 TC 16 Z9 17 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2012 VL 163 IS 3 BP 330 EP U269 DI 10.1016/j.ahj.2012.01.028 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 909WO UT WOS:000301597200007 PM 22424002 ER PT J AU Xian, Y Fonarow, GC Reeves, MJ Webb, LE Blevins, J Demyanenko, VS Zhao, X Olson, DM Hernandez, AF Peterson, ED Schwamm, LH Smith, EE AF Xian, Ying Fonarow, Gregg C. Reeves, Mathew J. Webb, Laura E. Blevins, Jason Demyanenko, Vladimir S. Zhao, Xin Olson, DaiWai M. Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. Smith, Eric E. TI Data quality in the American Heart Association Get With The Guidelines-Stroke (GWTG-Stroke): Results from a National Data Validation Audit SO AMERICAN HEART JOURNAL LA English DT Article ID TRANSIENT ISCHEMIC ATTACK; CARDIOVASCULAR RADIOLOGY; PERFORMANCE-MEASURES; OF-CARE; REGISTRY; PROGRAM; INTERVENTION; ADMISSIONS; OUTCOMES; COUNCIL AB Background Get With The Guidelines (GWTG)-Stroke is a national stroke registry and quality improvement program. We examined the accuracy and reliability of data entered in GWTG-Stroke. Methods Data entered by sites in the GWTG-Stroke database were compared with that abstracted from de-identified medical records by trained auditors. Accuracy for each individual data element and a composite accuracy measure were calculated. Reliability was assessed using kappa (kappa) statistics for categorical variables and intraclass correlation (ICC) for continuous variables. Results A random selection of 438 medical records from 147 GWTG-Stroke hospitals was obtained. Overall accuracy was above 90% for all variables abstracted except for weight (84.9%), serum creatinine (88.1%), deep venous thrombosis prophylaxis (79.0%), and date/time last known well (85.3%). Intermediate to good (kappa or ICC 0.40-0.75) or excellent agreement (kappa or ICC >= 0.75) was observed for nearly all audited variables, including time-related performance measures such as arrival within 2 hours of symptom onset (kappa >= 0.90) and door-to-needle time = 60 minutes (kappa >= 0.72). The overall composite accuracy rate was 96.1%. The composite measure varied slightly by region and hospital academic status, but there were no significant differences in composite accuracy by bed size, ischemic stroke volume, primary stroke center certification, or Coverdell Registry participation. Conclusions This audit establishes the reliability of GWTG-Stroke registry data. Individual data elements with suboptimal accuracy should be targeted for further data quality improvement. (Am Heart J 2012;163:392-398.e1.) C1 [Xian, Ying; Webb, Laura E.; Blevins, Jason; Demyanenko, Vladimir S.; Zhao, Xin; Olson, DaiWai M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27705 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Hotchkiss Brain Inst, Calgary, AB T2N 1N4, Canada. RP Xian, Y (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM ying.xian@dm.duke.edu RI Hernandez, Adrian F./A-7818-2016; OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668 FU Janssen Pharmaceutical Companies of Johnson Johnson; Boeringher-Ingelheim; Merck; Bristol-Myers Squib/Sanofi Pharmaceutical Partnership; American Heart Association Pharmaceutical Roundtable FX The GWTG-Stroke program is provided by the American Heart Association/American Stroke Association. The GWTG-Stroke program is currently supported, in part, by a charitable contribution from Janssen Pharmaceutical Companies of Johnson & Johnson. The GWTG-Stroke program has been funded in the past through support from Boeringher-Ingelheim, Merck, Bristol-Myers Squib/Sanofi Pharmaceutical Partnership, and the American Heart Association Pharmaceutical Roundtable. NR 18 TC 53 Z9 53 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2012 VL 163 IS 3 BP 392 EP U336 DI 10.1016/j.ahj.2011.12.012 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 909WO UT WOS:000301597200014 PM 22424009 ER PT J AU Hsich, EM Grau-Sepulveda, MV Hernandez, AF Peterson, ED Schwamm, LH Bhatt, DL Fonarow, GC AF Hsich, Eileen M. Grau-Sepulveda, Maria V. Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. Bhatt, Deepak L. Fonarow, Gregg C. TI Sex differences in in-hospital mortality in acute decompensated heart failure with reduced and preserved ejection fraction SO AMERICAN HEART JOURNAL LA English DT Article ID GENDER-RELATED DIFFERENCES; NATIONAL REGISTRY ADHERE; CLINICAL CHARACTERISTICS; AGE; COMMUNITY; OUTCOMES; TRENDS; TRIAL; CANDESARTAN; POPULATION AB Background There are no sex-specific survival comparisons between patients with heart failure (HF) with reduced and those with preserved ejection fraction. Large registries noting women have better survival than men combined HF patients with reduced and preserved EF. Other registries that compared patients with reduced and preserved EF did not analyze their data by sex. We sought to evaluate sex/EF differences in mortality and risk factors for survival in hospitalized patients with HF. Methods We included hospitals fully participating in Get With The Guidelines-Heart Failure that admitted HF patients with reduced (EF <40%) or preserved (EF >= 50%) EF. The primary end point was in-hospital mortality. Multivariate generalized estimating equation logistic models were used to compute odds ratios accounting for hospital clustering. Results The study cohort consisted of 51,428 patients with EF <40% (36% women, 64% men) and 37,699 patients with EF >= 50% (65% women, 35% men). Women compared with men with reduced and preserved EF were older and more likely to have hypertension, depression, or valvular heart disease and less likely to have coronary artery disease or peripheral vascular disease. There were no sex differences in in-hospital mortality (EF <40%, 2.69% women vs 2.89% men, P = .20; EF >= 50%, 2.61% women vs 2.62% men, P = .96), and risk factors such as age, systolic blood pressure, heart rate, and history of renal failure/dialysis were highly predictive of death for each sex/EF subgroup. Conclusions In a large, multicenter registry, we found that despite differences in baseline characteristics, women and men with reduced and preserved EF have similar in-hospital mortality and risk factors predicting death. (Am Heart J 2012;163:430-437.e3.) C1 [Hsich, Eileen M.] Cleveland Clin Fdn, Coll Med, Cleveland, OH 44195 USA. [Grau-Sepulveda, Maria V.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Ctr, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Div Cardiol, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. RP Hsich, EM (reprint author), Cleveland Clin, Kaufman Ctr Heart Failure, Inst Heart & Vasc, J3-4,9500 Euclid Ave, Cleveland, OH 44195 USA. EM Hsiche@ccf.org RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Medtronic, Inc.; GlaxoSmithKline; Ortho-McNeil; American Heart Association Pharmaceutical Roundtable; American Heart Association [0730307N]; Johnson Johnson; Amylin; Amarin; Astra Zeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; Medicines Company FX The Get With The Guidelines-Heart Failure (GWTG-HF) program is provided by the American Heart Association. The GWTG-HF program is currently supported, in part, by an unrestricted educational grant from Medtronic, Inc. It has been funded in the past through support from GlaxoSmithKline, Ortho-McNeil, and the American Heart Association Pharmaceutical Roundtable. Eileen Hsich receives funding from American Heart Association Scientist Development Grant 0730307N (E.H.). Adrian Hernandez receives funding from Johnson & Johnson and Amylin and has received honorarium from Amgen and Corthera. Deepak Bhatt receives funding from Amarin, Astra Zeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, and The Medicines Company. Gregg Fonarow is a consultant for Novartis. NR 36 TC 20 Z9 20 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2012 VL 163 IS 3 BP 430 EP U380 DI 10.1016/j.ahj.2011.12.013 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 909WO UT WOS:000301597200019 PM 22424014 ER PT J AU Troxel, AB Volpp, KG AF Troxel, Andrea B. Volpp, Kevin G. TI Effectiveness of Financial Incentives for Longer-Term Smoking Cessation: Evidence of Absence or Absence of Evidence? SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article ID CONTROLLED-TRIAL; PROGRAM C1 [Troxel, Andrea B.; Volpp, Kevin G.] Ctr Hlth Incent & Behav Econ, Leonard Davis Inst Hlth Econ, Philadelphia, PA USA. [Troxel, Andrea B.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Troxel, Andrea B.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Volpp, Kevin G.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Management, Philadelphia, PA 19104 USA. RP Volpp, KG (reprint author), 1120 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu OI Troxel, Andrea/0000-0002-1393-3075 FU NIA NIH HHS [P30 AG034546] NR 12 TC 7 Z9 7 U1 0 U2 7 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD MAR-APR PY 2012 VL 26 IS 4 BP 204 EP 207 DI 10.4278/ajhp.101111-CIT-371 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 908EK UT WOS:000301473000003 PM 22375568 ER PT J AU Separovic, D Breen, P Joseph, N Bielawski, J Pierce, JS Van Buren, E Gudz, TI AF Separovic, Duska Breen, Paul Joseph, Nicholas Bielawski, Jacek Pierce, Jason S. Van Buren, Eric Gudz, Tatyana I. TI Ceramide Synthase 6 Knockdown Suppresses Apoptosis after Photodynamic Therapy in Human Head and Neck Squamous Carcinoma Cells SO ANTICANCER RESEARCH LA English DT Article DE Apoptosis; ceramide; ceramide synthase 6; dihydroceramide; PDT; sphingolipids; head and neck squamous carcinoma; UM-SCC-22A cells ID LONGEVITY ASSURANCE GENE-1; DE-NOVO SPHINGOLIPIDS; PHOTOSENSITIZED CELLS; CANCER-CELLS; DEATH; ACCUMULATION; INHIBITION AB Background: The effectiveness of photodynamic therapy (PDT) for cancer treatment correlates with apoprosis. We observed that suppression of de nova-generated sphingolipids, e.g. ceramide, renders cells resistant to apoptosis post-PDT. Ceramide synthase 6 (CerS6) has been implicated in apoptosis after various stimuli. Aim: To investigate the involvement of down-regulation of CerS6 in apoptosis and its impact on the sphingolipid profile post-PDT with the silicone phthalocyanine Pc 4 in a human head and neck squamous carcinoma cell line. Materials and Methods: Besides siRNA transfections and PDT treatment, immunoblotting for protein expression, mass spectrometry for sphingolipid analysis, spectroflurometry and flow cytometry for apoptotic marker detection, and trypan blue assay for cytotoxicity assessment, were used. Results: CerS6 knockdown led to reduction in PDT-induced DEVDase activation, mitochondrial depolarization, apoptosis and cell death. CerS6 knockdown was associated with selective decreases in ceramides and dihydroceramides, markedly of C18-dihydroceramide, post-PDT. Conclusion: CerS6 might be a novel therapeutic target for regulating apoptotic resistance to PDT. C1 [Separovic, Duska; Breen, Paul; Joseph, Nicholas] Wayne State Univ, Eugene Applebaum Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, Detroit, MI 48201 USA. [Separovic, Duska; Van Buren, Eric] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. [Bielawski, Jacek; Pierce, Jason S.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Gudz, Tatyana I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. RP Separovic, D (reprint author), Wayne State Univ, Eugene Applebaum Coll Pharm & Hlth Sci, Dept Pharmaceut Sci, 259 Mack Ave, Detroit, MI 48201 USA. EM dseparovic@wayne.edu FU U.S. Public Health Service; National Cancer Institute, National Institutes of Health [R01 CA77475]; RR&D and BLRD programs; NCI [IPO1CA097132, P30 CA 138313]; NIH/NCRR SC COBRE [P20 RR017677]; NIH; National Center for Research Resources [C06 RR018823] FX This work was supported by U.S. Public Health Service Grant R01 CA77475 from the National Cancer Institute, National Institutes of Health (DS) and the Veterans Administration Merit Awards from RR&D and BLRD programs (TIG). The MS-related work was performed by the Lipidomics Shared Resource (Medical University of South Carolina), supported by NCI grants: IPO1CA097132 and P30 CA 138313 and NIH/NCRR SC COBRE Grant P20 RR017677. Laboratory space for the Lipidomics Shared Resource was supported by the NIH, grant C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. We thank Drs. Besim Ogretmen and Can Ewe Senkal for helpful discussions of the manuscript. NR 29 TC 15 Z9 16 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR PY 2012 VL 32 IS 3 BP 753 EP 760 PG 8 WC Oncology SC Oncology GA 910EE UT WOS:000301619200006 PM 22399588 ER PT J AU Albrecht, J Werth, VP AF Albrecht, Joerg Werth, Victoria P. TI Improving the Care of Our Patients Who Are Receiving Glucocorticoid Therapy SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material C1 [Werth, Victoria P.] Hosp Univ Penn, Dept Dermatol, Perelman Ctr Adv Med, Philadelphia, PA 19104 USA. [Albrecht, Joerg] John H Stroger Jr Hosp Cook Cty, Div Dermatol, Dept Med, Chicago, IL USA. [Werth, Victoria P.] Philadelphia Vet Affairs Med Ctr, Dept Dermatol, Philadelphia, PA USA. RP Werth, VP (reprint author), Hosp Univ Penn, Dept Dermatol, Perelman Ctr Adv Med, 3400 Civ Ctr Blvd,Ste 1-330S, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24-AR 02207, K24 AR002207] NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 2012 VL 148 IS 3 BP 314 EP 315 PG 2 WC Dermatology SC Dermatology GA 911BV UT WOS:000301693200005 PM 22431773 ER PT J AU Piette, EW Foering, KP Chang, AY Okawa, J Ten Have, TR Feng, R Werth, VP AF Piette, Evan W. Foering, Kristen P. Chang, Aileen Y. Okawa, Joyce Ten Have, Thomas R. Feng, Rui Werth, Victoria P. TI Impact of Smoking in Cutaneous Lupus Erythematosus SO ARCHIVES OF DERMATOLOGY LA English DT Article ID CIGARETTE-SMOKING; ALCOHOL-CONSUMPTION; TOBACCO-SMOKE; ASSOCIATION; RISK; TUMIDUS; MARKERS; LESIONS AB Objective: To investigate cigarette smoking in cutaneous lupus erythematosus (CLE). Design: Prospective longitudinal cohort study. Setting: Urban cutaneous autoimmune disease clinic. Participants: A total of 218 individuals with CLE or systemic lupus erythematosus and lupus nonspecific skin disease seen between January 5, 2007, and July 30, 2010. Main Outcome Measures: Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) scores to assess disease severity and response to treatment and Skindex 29+3 scores to assess patient quality of life. Results: Current smokers with lupus erythematosus had higher median CLASI scores (9.5) than did never (7.0) and past (6.0) smokers with CLE (P = .02). Current smokers had higher median scores on all the Skindex 29+3 subsets. Current smokers taking hydroxychloroquine sulfate had higher quinacrine hydrochloride use than did nonsmokers (P = .04). Two to 7 months after enrollment, current smokers (median CLASI change, 3) treated with only antimalarial agents improved more than never (1) and past (0) smokers (P = .02). Eight months or more after enrollment, current smokers (CLASI change, 3.5) treated with antimalarial drugs plus at least 1 additional immunomodulator improved less than never (-1.5) and past (0) smokers (P = .04). Conclusions: Current smokers with lupus erythematosus had worse disease, had worse quality of life, and were more often treated with a combination of hydroxychloroquine and quinacrine than were nonsmokers. Never and past smokers showed greater improvement when treated with antimalarial agents plus at least 1 additional immunomodulator. Current smokers had greater improvement when treated with antimalarial drugs only. C1 [Werth, Victoria P.] Univ Penn, Sch Med, Dept Dermatol, Perelman Ctr Adv Med, Philadelphia, PA 19104 USA. [Piette, Evan W.; Foering, Kristen P.; Chang, Aileen Y.; Okawa, Joyce; Ten Have, Thomas R.; Feng, Rui; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Ten Have, Thomas R.; Feng, Rui; Werth, Victoria P.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Univ Penn, Sch Med, Dept Dermatol, Perelman Ctr Adv Med, Ste 1-330A,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU National Institutes of Health [K24-AR 18 02207]; Celgene; Amgen FX This study is based on work supported by the National Institutes of Health, including grant K24-AR 18 02207 (Dr Werth).; The copyright for CLASI is owned by the University of Pennsylvania. Dr Werth has served as a consultant to Pfizer, Novartis, Cephalon, Rigel, and Medimmune and has received grant support from Celgene and Amgen. NR 24 TC 27 Z9 27 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 2012 VL 148 IS 3 BP 317 EP 322 DI 10.1001/archdermatol.2011.342 PG 6 WC Dermatology SC Dermatology GA 911BV UT WOS:000301693200006 PM 22105815 ER PT J AU Alloo, A Garibyan, L LeBoeuf, N Lin, G Werchniak, A Hodi, FS Flaherty, KT Lawrence, DP Lin, JY AF Alloo, Allireza Garibyan, Lilit LeBoeuf, Nicole Lin, George Werchniak, Andrew Hodi, F. Stephen, Jr. Flaherty, Keith T. Lawrence, Donald P. Lin, Jennifer Y. TI Photodynamic Therapy for Multiple Eruptive Keratoacanthomas Associated With Vemurafenib Treatment for Metastatic Melanoma SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; BRAF; CANCER; TUMOR; RAF AB Background: The development of keratoacanthomas (KAs) and well-differentiated squamous cell carcinomas (SCCs) is a known adverse effect of novel BRAF inhibitors such as vemurafenib. With multiple such neoplasms often arising after BRAF inhibitor therapy, surgical excision is often impractical. Observations: We describe a patient with stage IV melanoma who received the BRAF inhibitor vemurafenib (recently approved by the US Food and Drug Administration) as part of a clinical trial and developed numerous diffuse, pathology-proven KAs and SCCs. The high number of lesions across a broad area precluded surgical treatment; instead, a noninvasive field approach using photodynamic therapy (PDT) was initiated. Compared with untreated tumors, most lesions demonstrated significant clinical regression following successive cycles of PDT. Conclusions: Given vemurafenib's recent approval by the US Food and Drug Administration, we provide a timely case report on the effective use of PDT in the treatment of BRAF inhibitor associated KAs and SCCs. Although further studies are needed to better understand the biological processes of these secondary neoplasms, our observation provides an alternative noninvasive solution for improving the quality C1 [Lin, Jennifer Y.] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dana Farber Canc Inst, Dept Dermatol,Emmanuel Coll,Melanoma Program, Boston, MA 02115 USA. [Alloo, Allireza; Garibyan, Lilit; LeBoeuf, Nicole; Werchniak, Andrew; Lin, Jennifer Y.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Lin, George] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Flaherty, Keith T.; Lawrence, Donald P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. RP Lin, JY (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dana Farber Canc Inst, Dept Dermatol,Emmanuel Coll,Melanoma Program, Alumnae Hall,21 Ave Louis Pasteur, Boston, MA 02115 USA. EM jylin@partners.org NR 13 TC 24 Z9 25 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 2012 VL 148 IS 3 BP 363 EP 366 PG 4 WC Dermatology SC Dermatology GA 911BV UT WOS:000301693200012 PM 22431777 ER PT J AU Fett, N AF Fett, Nicole TI Gabapentin Not Shown to Prevent Postherpetic Neuralgia SO ARCHIVES OF DERMATOLOGY LA English DT Letter ID HERPES-ZOSTER; VACCINE C1 [Fett, Nicole] Univ Penn, Dept Dermatol, Sch Med, Perelman Ctr Adv Med, Philadelphia, PA 19104 USA. [Fett, Nicole] Univ Penn, Sch Med, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Fett, N (reprint author), Univ Penn, Dept Dermatol, Sch Med, Perelman Ctr Adv Med, 3400 Civ Ctr Blvd,Ste 1-330A, Philadelphia, PA 19104 USA. EM nicole.fett@uphs.upenn.edu NR 5 TC 2 Z9 3 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 2012 VL 148 IS 3 BP 400 EP 401 PG 2 WC Dermatology SC Dermatology GA 911BV UT WOS:000301693200026 PM 22431790 ER PT J AU Bergmark, R Jung, D Vakharia, K Gray, ST Lin, DT Rosenberg, AE AF Bergmark, Regan Jung, David Vakharia, Kalpesh Gray, Stacey T. Lin, Derrick T. Rosenberg, Andrew E. TI Pathology Quiz Case 1: Liposarcoma of the hypopharynx SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID TISSUE TUMORS; DIAGNOSIS; CDK4; HEAD; MDM2 C1 [Bergmark, Regan] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Jung, David; Vakharia, Kalpesh; Gray, Stacey T.; Lin, Derrick T.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Rosenberg, Andrew E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergmark, R (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAR PY 2012 VL 138 IS 3 BP 313 EP 315 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 911BW UT WOS:000301693300016 PM 22431879 ER PT J AU Hill, CA Maturo, S Gallagher, TQ Whelan, P Pasternack, MS Hartnick, CJ Kieff, DA AF Hill, Courtney A. Maturo, Stephen Gallagher, Thomas Q. Whelan, Patrick Pasternack, Mark S. Hartnick, Christopher J. Kieff, David A. TI Pathology Quiz Case 2: Diagnosis Laryngeal sarcoidosis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material C1 [Hill, Courtney A.; Maturo, Stephen; Gallagher, Thomas Q.; Hartnick, Christopher J.; Kieff, David A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Hill, Courtney A.; Maturo, Stephen; Gallagher, Thomas Q.; Hartnick, Christopher J.; Kieff, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Whelan, Patrick; Pasternack, Mark S.] MassGen Hosp Children, Boston, MA USA. RP Hill, CA (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD MAR PY 2012 VL 138 IS 3 BP 317 EP 319 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 911BW UT WOS:000301693300017 PM 22431880 ER PT J AU Hu, YY Fix, ML Hevelone, ND Lipsitz, SR Greenberg, CC Weissman, JS Shapiro, J AF Hu, Yue-Yung Fix, Megan L. Hevelone, Nathanael D. Lipsitz, Stuart R. Greenberg, Caprice C. Weissman, Joel S. Shapiro, Jo TI Physicians' Needs in Coping With Emotional Stressors The Case for Peer Support SO ARCHIVES OF SURGERY LA English DT Article ID PERCEIVED MEDICAL ERRORS; AMERICAN-SURGEONS; CAREER SATISFACTION; JOB-SATISFACTION; ADVERSE EVENTS; UNITED-STATES; 2ND VICTIM; BURNOUT; RESIDENTS; HEALTH AB Objective: To design an evidence-based intervention to address physician distress, based on the attitudes toward support among physicians at our hospital. Design, Setting, and Participants: A 56-item survey was administered to a convenience sample (n = 108) of resident and attending physicians at surgery, emergency medicine, and anesthesiology departmental conferences at a large tertiary care academic hospital. Main Outcome Measures: Likelihood of seeking support, perceived barriers, awareness of available services, sources of support, and experience with stress. Results: Among the resident and attending physicians, 79% experienced either a serious adverse patient event and/or a traumatic personal event within the preceding year. Willingness to seek support was reported for legal situations (72%), involvement in medical errors (67%), adverse patient events (63%), substance abuse (67%), physical illness (62%), mental illness (50%), and interpersonal conflict at work (50%). Barriers included lack of time (89%), uncertainty or difficulty with access (69%), concerns about lack of confidentiality (68%), negative impact on career (68%), and stigma (62%). Physician colleagues were the most popular potential sources of support (88%), outnumbering traditional mechanisms such as the employee assistance program (29%) and mental health professionals (48%). Based on these results, a one-on-one peer physician support program was incorporated into support services at our hospital. Conclusions: Despite the prevalence of stressful experiences and the desire for support among physicians, established services are underused. As colleagues are the most acceptable sources of support, we advocate peer support as the most effective way to address this sensitive but important issue. C1 [Shapiro, Jo] Brigham & Womens Hosp, Ctr Professionalism & Peer Support, Boston, MA 02115 USA. [Hu, Yue-Yung] Brigham & Womens Hosp, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Hu, Yue-Yung; Hevelone, Nathanael D.; Lipsitz, Stuart R.; Greenberg, Caprice C.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Weissman, Joel S.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Fix, Megan L.] Univ Utah Hosp, Salt Lake City, UT USA. RP Shapiro, J (reprint author), Brigham & Womens Hosp, Ctr Professionalism & Peer Support, 75 Francis St, Boston, MA 02115 USA. EM jshapiro@partners.org OI Hevelone, Nathanael/0000-0003-4740-2085 FU NCI NIH HHS [L30 CA123695-02]; NCRR NIH HHS [L30 RR031458-01]; NIDDK NIH HHS [T32 DK007754, T32 DK007754-12] NR 56 TC 33 Z9 33 U1 4 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAR PY 2012 VL 147 IS 3 BP 212 EP 217 DI 10.1001/archsurg.2011.312 PG 6 WC Surgery SC Surgery GA 910LC UT WOS:000301637200002 PM 22106247 ER PT J AU Martins, PN Varma, MC Elias, N Markmann, JF AF Martins, Paulo N. Varma, Manish C. Elias, Nahel Markmann, James F. TI Image of the Month Portal Vein Gas Associated With Pneumatosis Intestinalis SO ARCHIVES OF SURGERY LA English DT Editorial Material ID LIVER-TRANSPLANTATION C1 [Martins, Paulo N.; Varma, Manish C.; Elias, Nahel; Markmann, James F.] Harvard Univ, Div Transplantat, Dept Surg, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Martins, PN (reprint author), Harvard Univ, Div Transplantat, Dept Surg, Massachusetts Gen Hosp,Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM pnmartins@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAR PY 2012 VL 147 IS 3 BP 291 EP 292 PG 2 WC Surgery SC Surgery GA 910LC UT WOS:000301637200021 PM 22430916 ER PT J AU Whitesell, L Lin, NU AF Whitesell, Luke Lin, Nancy U. TI HSP90 as a platform for the assembly of more effective cancer chemotherapy SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE Combination chemotherapy; Clinical trial; Drug resistance; Cancer evolution ID PHASE-II TRIAL; SHOCK-PROTEIN 90; REFRACTORY ADVANCED CANCERS; TYROSINE KINASE INHIBITORS; METASTATIC PROSTATE-CANCER; C-TERMINAL DOMAIN; CELL LUNG-CANCER; BREAST-CANCER; DRUG-RESISTANCE; SOLID TUMORS AB Since initial discovery of the first HSP90 inhibitor over a decade and a half ago, tremendous progress has been made in developing potent and selective compounds with which to target this chaperone in the treatment of cancers. These compounds have been invaluable in dissecting how HSP90 supports the dramatic alterations in cellular physiology that constitute the malignant phenotype and give rise to the clinical manifestations of diverse cancers. Unfortunately. single agent activity for HSP90 inhibitors has been disappointingly modest against recurrent, refractory cancers in most of the clinical trials that have been reported to date. This problem could be due to pharmacological limitations of the first-generation inhibitors that have been most extensively studied. But we suggest it may well be intrinsic to the target itself. This review will focus on how the utilization of HSP90 by cancer cells might be targeted to enhance the activity of other anticancer drugs while at the same time limiting the ability of advanced cancers to adapt and evolve drug resistance; the net result being more durable disease control. A better understanding of these fundamental issues will surely make the ongoing clinical development of HSP90 inhibitors as anticancer drugs less empiric, more efficient and hopefully more successful. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90). (C) 2012 Elsevier B.V. All rights reserved. C1 [Whitesell, Luke] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Lin, Nancy U.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Whitesell, L (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM whitesell@wi.mit.edu; Nancy_Lin@dfci.harvard.edu FU Komen Foundation; U.S. Department of Defense; Johnson and Johnson Focused Funding Program FX Sincere thanks go to S. Lindquist and members of her lab for insights and advice. LW. is supported in part by funds from the Komen Foundation, U.S. Department of Defense and Johnson and Johnson Focused Funding Program. We apologize to our many peers whose important work in this rapidly advancing field could not be cited owing to space limitations. Their contributions to advancing our understanding of HSP90 and improving the outcome for cancer patients is much appreciated. NR 127 TC 49 Z9 50 U1 0 U2 12 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 MAR PY 2012 VL 1823 IS 3 SI SI BP 756 EP 766 DI 10.1016/j.bbamcr.2011.12.006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 910HV UT WOS:000301628700018 PM 22222203 ER PT J AU Kolodziej, AF Nair, SA Graham, P McMurry, TJ Ladner, RC Wescott, C Sexton, DJ Caravan, P AF Kolodziej, Andrew F. Nair, Shrikumar A. Graham, Philip McMurry, Thomas J. Ladner, Robert C. Wescott, Charles Sexton, Daniel J. Caravan, Peter TI Fibrin Specific Peptides Derived by Phage Display: Characterization of Peptides and Conjugates for Imaging SO BIOCONJUGATE CHEMISTRY LA English DT Article ID TARGETED CONTRAST AGENT; SINGLE-CHAIN ANTIBODY; MONOCLONAL-ANTIBODIES; CORONARY-THROMBOSIS; PULMONARY EMBOLI; SWINE MODEL; FACTOR XA; BINDING; EP-2104R; MRI AB Peptides that bind to fibrin but not to fibrinogen or serum albumin were selected from phage display libraries as targeting moieties for thrombus molecular imaging probes. Three classes of cyclic peptides (cyclized via disulfide bond between two Cys) were identified with consensus sequences XArXCPY(G/D)LCArIX (Ar = aromatic, Tn6), X(2)CXYYGTCLX (Tn7), and NHGCYNSYGVPYCDYS (Tn10). These peptides bound to fibrin at similar to 2 sites with K-d = 4.1 mu M, 4.0 mu M, and 8.7 mu M, respectively, whereas binding to fibrinogen was at least 100-fold weaker. The peptides also bind to the fibrin degradation product DD(E) with similar affinity to that measured for fibrin. The Tn7 and Tn10 peptides bind to the same site on fibrin, while the Tn6 peptides bind to a unique site. Alanine scanning identified the N- and C-terminal ends of the Tn6 and Tn7 peptides as most tolerant to modification. Peptide conjugates with either fluorescein or diethylenetriaminepentaaceto gadolinium(III) (GdDTPA) at the N-terminus were prepared for potential imaging applications, and these retained fibrin binding affinity and specificity in plasma. Relaxivity and binding studies on the GdDTPA derivatives revealed that an N-terminal glycyl linker had a modest effect on fibrin affinity but resulted in lower fibrin-bound relaxivity. C1 [Caravan, Peter] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kolodziej, Andrew F.; Nair, Shrikumar A.; Graham, Philip; McMurry, Thomas J.] EPIX Pharmaceut Inc, Cambridge, MA USA. [Ladner, Robert C.; Wescott, Charles; Sexton, Daniel J.] Dyax Corp, Cambridge, MA USA. [Caravan, Peter] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Caravan, P (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Suite 2301,149 13th St, Charlestown, MA 02129 USA. EM caravan@nmr.mgh.harvard.edu FU National Institute of Neurological Disorders and Stroke [R21NS075627] FX This work was supported in part by Award Number R21NS075627 from the National Institute of Neurological Disorders and Stroke to P.C. NR 33 TC 26 Z9 26 U1 7 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR PY 2012 VL 23 IS 3 BP 548 EP 556 DI 10.1021/bc200613e PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 911EN UT WOS:000301700200026 PM 22263840 ER PT J AU Schneider, JC Qu, HGD Lowry, J Walker, J Vitale, E Zona, M AF Schneider, Jeffrey C. Qu, Huaguang D. Lowry, John Walker, Joseph Vitale, Elizabeth Zona, Marissa TI Efficacy of inpatient burn rehabilitation: A prospective pilot study examining range of motion, hand function and balance SO BURNS LA English DT Article DE Burns; Contractures; Hand function; Jebsen Hand Function Test; Balance; Berg Balance Scale; Rehabilitation; Functional outcome ID POSTBURN CONTRACTURE; SCAR CONTRACTURES; INJURY; FLAP; RELEASE; SPLINT; NECK; PREVENTION; EXPERIENCE; MANAGEMENT AB Purpose: To examine the effect of inpatient rehabilitation therapy on range of motion, hand function and balance in the burn population. Methods: This study utilizes a prospective longitudinal design. Inclusion criteria are adults admitted to a regional inpatient rehabilitation hospital with a primary diagnosis of burn injury. Demographic and medical data are collected. Primary outcomes include range of motion at four joints (shoulder, elbow, hip, knee), hand function (Jebsen Taylor Hand Test) and balance (Berg Balance Scale). Outcomes are measured at admission and discharge. Students' t-test is used to determine significant differences in outcomes from admission to discharge. Results: Eleven subjects meet inclusion criteria. The mean age is 50 years, rehabilitation length of stay is 35 days and total body surface area burned is 41%. Subjects demonstrate significant improvements in range of motion, hand function and balance from admission to discharge (p < 0.05). Conclusions: Specific functional measures, range of motion, hand function and balance, demonstrate significant improvement during inpatient rehabilitation. Future work is needed to investigate other functional benefits of rehabilitation and to compare the impact of inpatient rehabilitation to other therapeutic interventions. (C) 2011 Elsevier Ltd and ISBI. All rights reserved. C1 [Schneider, Jeffrey C.; Qu, Huaguang D.; Lowry, John] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Walker, Joseph] Univ Connecticut, Ctr Hlth, Dept Orthoped Surg, Farmington, CT USA. [Vitale, Elizabeth] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. [Zona, Marissa] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Occupat Therapy, Boston, MA 02114 USA. RP Schneider, JC (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. EM jcschneider@partners.org NR 57 TC 13 Z9 15 U1 3 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD MAR PY 2012 VL 38 IS 2 BP 164 EP 171 DI 10.1016/j.burns.2011.11.002 PG 8 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA 910FB UT WOS:000301621500003 PM 22119446 ER PT J AU McKiernan, SH Colman, RJ Aiken, E Evans, TD Beasley, TM Aiken, JM Weindruch, R Anderson, RM AF McKiernan, Susan H. Colman, Ricki J. Aiken, Erik Evans, Trent D. Beasley, T. Mark Aiken, Judd M. Weindruch, Richard Anderson, Rozalyn M. TI Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Rhesus monkey; Calorie restriction; Sarcopenia; Aged ID DNA-DELETION MUTATIONS; DIETARY RESTRICTION; MITOCHONDRIAL ABNORMALITIES; FIBER ATROPHY; ADULT MALE; LIFE-SPAN; SARCOPENIA; SIZE; PHENOTYPES; ONSET AB We have previously shown that a 30% reduced calorie intake diet delayed the onset of muscle mass loss in adult monkeys between similar to 16 and similar to 22 years of age and prevented multiple cellular phenotypes of aging. In the present study we show the impact of long term (similar to 17 years) calorie restriction (CR) on muscle aging in very old monkeys (27-33 yrs) compared to age-matched Control monkeys fed ad libitum, and describe these data in the context of the whole longitudinal study. Muscle mass was preserved in very old calorie restricted (CR) monkeys compared to age-matched Controls. Immunohistochemical analysis revealed an age-associated increase in the proportion of Type I fibers in the VL from Control animals that was prevented with CR. The cross sectional area (CSA) of Type II fibers was reduced in old CR animals compared to earlier time points (16-22 years of age); however, the total loss in CSA was only 15% in CR animals compared to 36% in old Controls at similar to 27 years of age. Atrophy was not detected in Type I fibers from either group. Notably, Type I fiber CSA was similar to 1.6 fold greater in VL from CR animals compared to Control animals at similar to 27 years of age. The frequency of VL muscle fibers with defects in mitochondrial electron transport system enzymes (ETSab), the absence of cytochrome c oxidase and hyper-reactive succinate dehydrogenase, were identical between Control and CR. We describe changes in ETSab fiber CSA and determined that CR fibers respond differently to the challenge of mitochondria! deficiency. Fiber counts of intact rectus femoris muscles revealed that muscle fiber density was preserved in old CR animals. We suggest that muscle fibers from CR animals are better poised to endure and adapt to changes in muscle mass than those of Control animals. (C) 2011 Elsevier Inc. All rights reserved. C1 [McKiernan, Susan H.; Aiken, Erik] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. [McKiernan, Susan H.; Colman, Ricki J.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. [Evans, Trent D.; Weindruch, Richard; Anderson, Rozalyn M.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Beasley, T. Mark] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Aiken, Judd M.] Univ Alberta, Dept Agr Food & Nutr Sci, Edmonton, AB T6G 2M8, Canada. [Weindruch, Richard; Anderson, Rozalyn M.] Univ Wisconsin, William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. RP McKiernan, SH (reprint author), Univ Wisconsin, Dept Kinesiol, 2000 Observ Dr, Madison, WI 53706 USA. EM shmckier@wisc.edu; rmanderson5@wisc.edu FU NIH [P01 AG-11915, P51 RR000167]; Ellison Medical Foundation; Research Facilities Improvement Program [RR15459-01, RR020141-01] FX We acknowledge the efforts of the veterinary staff of the Wisconsin National Primate Research Center. This work was supported by NIH grants P01 AG-11915; P51 RR000167, and the Ellison Medical Foundation Senior Scholar Award (JMA). This research was conducted in part at a facility constructed with support from the Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. NR 35 TC 15 Z9 15 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAR PY 2012 VL 47 IS 3 BP 229 EP 236 DI 10.1016/j.exger.2011.12.009 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 911BR UT WOS:000301692800004 PM 22226624 ER PT J AU Chung, RT Umbleja, T Chen, JY Andersen, JW Butt, AA Sherman, KE AF Chung, Raymond T. Umbleja, Triin Chen, Jennifer Y. Andersen, Janet W. Butt, Adeel A. Sherman, Kenneth E. CA ACTG A5178 Study Team TI Extended Therapy With Pegylated Interferon and Weight-Based Ribavirin for HCV-HIV Coinfected Patients SO HIV CLINICAL TRIALS LA English DT Article DE extended therapy; HCV; HIV; weight-based ribavirin ID HEPATITIS-C-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; SUSTAINED VIROLOGICAL RESPONSE; INFECTED PATIENTS; RANDOMIZED-TRIAL; PEGINTERFERON ALPHA-2B; TREATMENT DURATION; GENETIC-VARIATION; GENOTYPE 1 AB Background: It is unknown whether extended treatment with pegylated interferon (PEG) and weight-based ribavirin (WBR) results in higher rates of sustained virologic response (SVR) among HCV-HIV coinfected patients compared with standard duration therapy. Objective: The study aimed to measure rates of SVR among coinfected patients who received extended therapy with PEG plus WBR. Methods: HCV-HIV coinfected subjects were treated with PEG and WBR, and those who achieved early virologic response (EVR; >= 2 log decrease in HCV RNA from baseline or HCV RNA<600 IU/mL) at week 12 were eligible to continue treatment for 72 weeks. SVR (HCV RNA<60 IU/mL) was measured 24 weeks after treatment discontinuation. Predictors of SVR were assessed in simple and multivariate logistic regression. Results: A total of 329 subjects enrolled at 36 sites. Of 184 subjects who achieved EVR, 169 entered Step 3: 89% male, 52% White, 29% Black, and 71% HCV treatment naive. The overall SVR rate was 27% (95% CI, 22%-32%) among all subjects, and 33% (95% CI, 27%-40%) among the 223 who were HCV treatment naive. In exploratory analyses, among 120 treatment-naive subjects who entered Step 3, the SVR rate was 62% (95% CI, 52%-70%). In this subgroup, predictors of SVR were HCV genotype 2 or 3 (P = .03), HCV RNA <800,000 IU/mL at study entry (P = .05), and achievement of complete EVR (HCV RNA<600 IU/mL at week 12; P < .0001). Conclusion: Among all subjects, we observed a comparable overall SVR rate to prior studies of subjects treated for 48 weeks. Extended treatment with PEG and WBR may be beneficial to subsets of coinfected patients, specifically those who are treatment naive and achieve complete EVR. C1 [Chung, Raymond T.] Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. [Umbleja, Triin; Andersen, Janet W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Chen, Jennifer Y.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Butt, Adeel A.] Univ Pittsburgh, Pittsburgh, PA USA. [Sherman, Kenneth E.] Univ Cincinnati, Cincinnati, OH USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, GI Unit, GRJ724,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU NIAID [U01 AI068634, U01 AI38858, U01 AI068636, K24 DK078772, K24 DK070528]; General Clinical Research Center Units; National Center for Research Resources FX Funding/Support: The project described was supported by NIAID funding to the ACTG including U01 AI068634, U01 AI38858, U01 AI068636, K24 DK078772 (to R.T.C.), K24 DK070528 (to K.E.S.) and also supported in part by the General Clinical Research Center Units funded by the National Center for Research Resources. Study drug and other support were provided by Roche Pharmaceuticals. NR 33 TC 7 Z9 8 U1 0 U2 1 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD MAR-APR PY 2012 VL 13 IS 2 BP 70 EP 82 DI 10.1310/hct1302-70 PG 13 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 913RC UT WOS:000301894100002 PM 22510354 ER PT J AU Bradshaw, AD AF Bradshaw, Amy D. TI Diverse biological functions of the SPARC family of proteins SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE SPL-1; SMOC; Testican; fstl-1; Hevin; SPOCK; Review ID FOLLISTATIN-LIKE PROTEIN-1; THYROGLOBULIN TYPE-1 DOMAIN; CALCIUM-BINDING PROTEIN; INTEGRIN-LINKED KINASE; NULL MICE; MATRIX-METALLOPROTEINASE; EXTRACELLULAR-MATRIX; MATRICELLULAR PROTEINS; RHEUMATOID-ARTHRITIS; MMP-2 EXPRESSION AB The SPARC family of proteins represents a diverse group of proteins that modulate cell interaction with the extracellular milieu. The eight members of the SPARC protein family are modular in nature. Each shares a follistatin-like domain and an extracellular calcium binding E-F hand motif. In addition, each family member is secreted into the extracellular space. Some of the shared activities of this family include, regulation of extracellular matrix assembly and deposition, counter-adhesion, effects on extracellular protease activity, and modulation of growth factor/cytokine signaling pathways. Recently, several SPARC family members have been implicated in human disease pathogenesis. This review discusses recent advances in the understanding of the functional roles of the SPARC family of proteins in development and disease. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Bradshaw, Amy D.] Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. [Bradshaw, Amy D.] Ralph H Johnson Vet Adm, Charleston, SC USA. RP Bradshaw, AD (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, 114 Doughty St, Charleston, SC 29425 USA. EM bradshad@musc.edu FU NIH, NIHLB [094517]; Veteran's Administration FX This was supported in part by the NIH, NIHLB through 094517 (ADB), and a Merit Award from the Veteran's Administration to ADB. NR 80 TC 67 Z9 68 U1 1 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD MAR PY 2012 VL 44 IS 3 BP 480 EP 488 DI 10.1016/j.biocel.2011.12.021 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 913YU UT WOS:000301914100011 PM 22249026 ER PT J AU Gandhi, RT Coombs, RW Chan, ES Bosch, RJ Zheng, L Margolis, DM Read, S Kallungal, B Chang, M Goecker, EA Wiegand, A Kearney, M Jacobson, JM D'Aquila, R Lederman, MM Mellors, JW Eron, JJ AF Gandhi, Rajesh T. Coombs, Robert W. Chan, Ellen S. Bosch, Ronald J. Zheng, Lu Margolis, David M. Read, Sarah Kallungal, Beatrice Chang, Ming Goecker, Erin A. Wiegand, Ann Kearney, Mary Jacobson, Jeffrey M. D'Aquila, Richard Lederman, Michael M. Mellors, John W. Eron, Joseph J. CA AIDS Clinical Trials Grp ACTG A524 TI No Effect of Raltegravir Intensification on Viral Replication Markers in the Blood of HIV-1-Infected Patients Receiving Antiretroviral Therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; HIV-1 DNA; raltegravir; viral replication; reservoirs; 2-LTR circles; T-cell activation ID T-CELL-ACTIVATION; LOW-LEVEL VIREMIA; INFECTED PATIENTS; HIV-1 INFECTION; SUPPRESSION; CIRCLES; BURDEN; PLASMA; ADULTS; TRIAL AB Background: Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication. Methods: We previously reported the outcome of a randomized placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA,50 copies per milliliter that showed no effect on residual viremia measured by single copy assay. We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication as follows: 2-LTR HIV-1 circles, total cellular HIV-1 DNA, and T-cell activation. Results: Of 50 patients tested, 12 (24%) had 2-LTR circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T-cell activation. Conclusions: In HIV-1-infected individuals on effective ART, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection. C1 [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA. [Coombs, Robert W.; Chang, Ming; Goecker, Erin A.] Univ Washington, Sch Med, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Coombs, Robert W.] Univ Washington, Sch Med, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA. [Chan, Ellen S.; Bosch, Ronald J.; Zheng, Lu; Eron, Joseph J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Margolis, David M.] Univ N Carolina, Ctr Infect Dis, Chapel Hill, NC USA. [Read, Sarah] NIAID, HIV Res Branch, Bethesda, MD 20892 USA. [Kallungal, Beatrice] Social & Sci Syst Inc, ACTG Operat Ctr, Silver Spring, MD USA. [Wiegand, Ann; Kearney, Mary] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Jacobson, Jeffrey M.] Drexel Univ, Div Infect Dis & HIV Med, Philadelphia, PA 19104 USA. [D'Aquila, Richard] Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37212 USA. [Lederman, Michael M.] Case Western Reserve Univ, Div Infect Dis & HIV Med, Cleveland, OH 44106 USA. [Mellors, John W.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, GRJ 504,55 Fruit St, Boston, MA 02114 USA. EM rgandhi@partners.org OI Margolis, David/0000-0001-5714-0002 FU National Institute of Allergy and Infectious Diseases [U01AI068636, AI 068634]; Virology Support Laboratory of the AIDS Clinical Trials Group Central Group [204VC009, 1U01AI068636]; National Cancer Institute/Science Applications International Corporation [25XS119]; National Institute of Health [R01 AI066992-04A1, G08LM008830-01, U01 AI 694722]; Harvard University Center for AIDS Research (National Institute of Health) [2P30 AI060354-06]; University of Washington Center for AIDS Research [P30-AI-27757]; AIDS Clinical Trials Group Virology Specialty Laboratory [AI-38858]; Roche Molecular Systems; Merck Sharp and Dohme, Corp.; Tibotec; Gilead; Merck; Bristol-Myers Squibb; GlaxoSmithKline/Viiv; Virco; San Francisco General Hospital CTU [5UO1 AI069502-03]; MetroHealth CTU [AI 069501]; BSN-University of North Carolina AIDS Clinical Trials Unit CTU [AI69423-03]; CFAR [AI50410]; CTSA [RR025747]; Alabama Therapeutics CRS CTU [U01 AI069452]; GCRC [M01 RR-00032, RR025780, 5-MO1 RR00044]; Yandow, RN, BSN-Harvard Massachusetts General Hospital CTU [1U01AI069472]; PA-C-Stanford University CTU [AI069556]; RN-University of Pittsburgh CTU [AI 069494-01]; BSN-Washington University in St. Louis CTU [AI069495]; RN-Northwestern University CTU [AI069471]; HIV Prevention and Treatment CRS; NYC HHC at Bellevue Hospital Center [AI069532, AI-27665]; University of Washington, Seattle CTU [AI069434]; Cornell CTU [AI069419]; Beth Israel Deaconess (Partners/Harvard) CTU [U01 AI069472-04]; Harbor UCLA Medical Center CTU [AI069424]; Colorado ACTU CTU [AI069450]; University of Rochester CTU [AI69511-02]; Duke University Medical Center CTU [5U01 AI069484]; Harlem Family Health Center CTU [AI069470]; [AI-68636] FX Supported by Award Number U01AI068636 from the National Institute of Allergy and Infectious Diseases. The project was also supported by a grant from the National Institute of Allergy and Infectious Diseases to the Statistical and Data Analysis Center (AI 068634). In addition, J.W.M. was supported by Virology Support Laboratory subcontract (204VC009) of the AIDS Clinical Trials Group Central Group Grant (1U01AI068636) and by National Cancer Institute/Science Applications International Corporation Contract 25XS119. R.T.G. is supported by National Institute of Health R01 AI066992-04A1 and National Institute of Health G08LM008830-01 and by grants to the AIDS Clinical Trials Group (National Institute of Health U01 AI 694722) and the Harvard University Center for AIDS Research (National Institute of Health 2P30 AI060354-06). The Case Western Reserve Immunology Specialty Laboratory is supported by grant AI-68636. R.W.C. received support from the University of Washington Center for AIDS Research (P30-AI-27757) and the AIDS Clinical Trials Group Virology Specialty Laboratory (AI-38858). R.W.C. has received grant support from Roche Molecular Systems and served as a consultant to Abbott Laboratories. The study was also supported in by a research grant from the Investigator-Initiated Studies Program of Merck Sharp and Dohme, Corp.; R.T.G. has received grant support from Tibotec and Gilead. D.M.M. has served as a consultant and received grant support from Merck, Bristol-Myers Squibb, and Tibotec. J.W.M. is a consultant for Gilead Sciences, Merck, and RFS Pharma and owns share options in RFS Pharma. M.M.L. has served as a consultant to Merck. J.J.E. has served as a consultant and received grant support from Merck and GlaxoSmithKline/Viiv and has served as a consultant for Bristol-Myers Squibb, Tibotec, Gilead, and Tobira. R.D. has received grant support from Merck and Virco and served as a consultant to Tibotec.; We would like to thank all the members of the AIDS Clinical Trials Group A5244 team, including Randi Leavitt, John Coffin, Sarah Palmer, Carla Pettinelli, Ana Martinez, Lisa M. Demeter, Barbara Philpotts, Betty A. Donoval, and Robert Levaro. We would like to express our special appreciation to Nadia Alatrakchi at Beth Israel Deaconess Hospital and Kathy Medvik at Case Western Reserve University for performing and analyzing the immunology assays; to Jennifer Janik for her excellent work as the study data manager; and to Heather Sprenger and Amy Jennings for their outstanding work on coordinating the laboratory data for the study. We gratefully acknowledge the hard work of the study staff at all the AIDS Clinical Trials Group sites who screened and enrolled patients in this trial: Annie Luetkemeyer, MD and Joann Volinski, RN-UCSF, San Francisco General Hospital (Site 801) CTU Grant # 5UO1 AI069502-03; MetroHealth (Site 2503) CTU Grant # AI 069501; David Currin RN and Cheryl Marcus RN, BSN-University of North Carolina AIDS Clinical Trials Unit (Site 3201) CTU Grant # AI69423-03, CFAR Grant # AI50410, CTSA Grant # RR025747; Melinda Robertson, RN and Rebecca Creamer-Alabama Therapeutics CRS (Site 5801) CTU Grant # U01 AI069452, GCRC Grant # M01 RR-00032; Amy Sbrolla, RN and Nicole Burgett-Yandow, RN, BSN-Harvard Massachusetts General Hospital (Site 101) CTU Grant# 1U01AI069472; Jane Norris, PA-C and Sandra Valle, PA-C-Stanford University (Site 501) CTU Grant # AI069556; Deborah McMahon, MD and Sally McNulty, BA, RN-University of Pittsburgh (Site 1001) CTU Grant # AI 069494-01; Teresa Spitz, RN, CCRC and Judy Frain, RN, BSN-Washington University in St. Louis (Site 2101) CTU Grant # AI069495; Babafemi Taiwo, MBBS, MD and Karen Coleman, RN-Northwestern University (Site 2701) CTU Grant # AI069471; HIV Prevention and Treatment CRS (Site 30329); Margarita Vasquez, RN and Judith A. Aberg, MD-New York University/NYC HHC at Bellevue Hospital Center (Site 401) CTU Grant # AI069532, AI-27665; University of Washington, Seattle (Site 1401) CTU Grant #AI069434; Todd Stroberg, RN, and Valery Hughes NP-Cornell CTU (Site 7804) CTU Grant # AI069419 CTSC# RR024996; Mary Albrecht, MD and Amanda Youmans, RN, ANP-Beth Israel Deaconess (Partners/Harvard) (Site 103) CTU Grant # U01 AI069472-04; Harbor UCLA Medical Center (Site 603) CTU Grant #AI069424; M. Graham Ray, RN, MSN and Steven C. Johnson, MD-Colorado ACTU (Site 6101) CTU Grant #AI069450 and GCRC Grant # RR025780; Amneris Luque MD and Mary Adams, RN-University of Rochester (Site 1101) CTU Grant # AI69511-02 (as of 2/12/08), GCRC Grant # 5-MO1 RR00044; Nathan M. Thielman, MD and Martha Silberman, RN-Duke University Medical Center (Site 1601) CTU Grant # 5U01 AI069484; Harlem Family Health Center (Site 31483) CTU Grant # AI069470. Finally, we would like to thank all the patients who participated in this study NR 20 TC 54 Z9 54 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2012 VL 59 IS 3 BP 229 EP 235 DI 10.1097/QAI.0b013e31823fd1f2 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 898UJ UT WOS:000300767400007 PM 22083073 ER PT J AU Rich, ML Miller, AC Niyigena, P Franke, MF Niyonzima, JB Socci, A Drobac, PC Hakizamungu, M Mayfield, A Ruhayisha, R Epino, H Stulac, S Cancedda, C Karamaga, A Niyonzima, S Yarbrough, C Fleming, J Amoroso, C Mukherjee, J Murray, M Farmer, P Binagwaho, A AF Rich, Michael L. Miller, Ann C. Niyigena, Peter Franke, Molly F. Niyonzima, Jean Bosco Socci, Adrienne Drobac, Peter C. Hakizamungu, Massudi Mayfield, Alishya Ruhayisha, Robert Epino, Henry Stulac, Sara Cancedda, Corrado Karamaga, Adolph Niyonzima, Saleh Yarbrough, Chase Fleming, Julia Amoroso, Cheryl Mukherjee, Joia Murray, Megan Farmer, Paul Binagwaho, Agnes TI Excellent Clinical Outcomes and High Retention in Care Among Adults in a Community-Based HIV Treatment Program in Rural Rwanda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; CD4 lymphocyte count; community health worker; developing countries; HIV/AIDS; treatment outcome ID SUB-SAHARAN AFRICA; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNOLOGICAL OUTCOMES; TREATMENT SERVICE; COTE-DIVOIRE; SOUTH-AFRICA; SCALING-UP; ADHERENCE; HAITI; METAANALYSIS AB Background: Access to antiretroviral therapy (ART) has rapidly expanded; as of the end of 2010, an estimated 6.6 million people are receiving ART in low-income and middle-income countries. Few reports have focused on the experiences of rural health centers or the use of community health workers. We report clinical and programatic outcomes at 24 months for a cohort of patients enrolled in a community-based ART program in southeastern Rwanda under collaboration between Partners In Health and the Rwandan Ministry of Health. Methods and Findings: A retrospective medical record review was performed for a cohort of 1041 HIV+ adult patients initiating community-based ART between June 1, 2005, and April 30, 2006. Key programatic elements included free ART with direct observation by community health worker, tuberculosis screening and treatment, nutritional support, a transportation allowance, and social support. Among 1041 patients who initiated community-based ART, 961 (92.3%) were retained in care, 52 (5%) died and 28 (2.7%) were lost to follow-up. Median CD4 T-cell count increase was 336 cells per microliter [interquartile range: (IQR): 212-493] from median 190 cells per microliter (IQR: 116-270) at initiation. Conclusions: A program of intensive community-based treatment support for ART in rural Rwanda had excellent outcomes in 24-month retention in care. Having committed to improving access to HIV treatment in sub-Saharan Africa, the international community, including country HIV programs, should set high programmatic outcome benchmarks. C1 [Miller, Ann C.; Franke, Molly F.; Mukherjee, Joia; Farmer, Paul; Binagwaho, Agnes] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Rich, Michael L.; Drobac, Peter C.; Stulac, Sara; Cancedda, Corrado; Mukherjee, Joia; Murray, Megan; Farmer, Paul] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Rich, Michael L.; Franke, Molly F.; Socci, Adrienne; Drobac, Peter C.; Epino, Henry; Stulac, Sara; Cancedda, Corrado; Amoroso, Cheryl; Mukherjee, Joia; Farmer, Paul] Partners Hlth, Boston, MA USA. [Rich, Michael L.; Niyigena, Peter; Franke, Molly F.; Niyonzima, Jean Bosco; Socci, Adrienne; Drobac, Peter C.; Hakizamungu, Massudi; Mayfield, Alishya; Epino, Henry; Stulac, Sara; Cancedda, Corrado; Yarbrough, Chase; Fleming, Julia; Amoroso, Cheryl; Farmer, Paul] Partners Hlth Inshuti Mu Buzima, Rwinkwavu, Rwanda. [Ruhayisha, Robert; Karamaga, Adolph; Niyonzima, Saleh; Binagwaho, Agnes] Rwanda Minist Hlth, Kigali, Rwanda. [Epino, Henry] Massachusetts Gen Hosp, Div Emergency Med, Boston, MA 02114 USA. [Murray, Megan] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Miller, AC (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, 641 Huntington Ave, Boston, MA 02115 USA. EM ann_miller@hms.harvard.edu FU Partners In Health, a 501(c)(3) charity; Clinton Health Access Initiative; World Food Program FX Supported by funding from Partners In Health, a 501(c)(3) charity.; We would like to thank the patients, CHWs, and health care providers who comprised the community-based ART program in the southern Kayonza District and Kirehe Districts. We acknowledge the contributions of the following individuals to this article: Melissa Gilloolly, Patrick Manyika, and Minda Nicolas. We wish to acknowledge the leadership of the Rwandan MoH and the generous support of the Clinton Health Access Initiative and the World Food Program. NR 38 TC 65 Z9 65 U1 2 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2012 VL 59 IS 3 BP E35 EP E42 DI 10.1097/QAI.0b013e31824476c4 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 898UJ UT WOS:000300767400002 PM 22156912 ER PT J AU Travis, LB Ng, AK Allan, JM Pui, CH Kennedy, AR Xu, XG Purdy, JA Applegate, K Yahalom, J Constine, LS Gilbert, ES Boice, JD AF Travis, Lois B. Ng, Andrea K. Allan, James M. Pui, Ching-Hon Kennedy, Ann R. Xu, X. George Purdy, James A. Applegate, Kimberly Yahalom, Joachim Constine, Louis S. Gilbert, Ethel S. Boice, John D., Jr. TI Second Malignant Neoplasms and Cardiovascular Disease Following Radiotherapy SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CHILDHOOD-CANCER SURVIVOR; NON-HODGKINS-LYMPHOMA; LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; US RADIOLOGIC TECHNOLOGISTS; CONTRALATERAL BREAST-CANCER; IONIZING-RADIATION EXPOSURE; ACUTE MYELOID-LEUKEMIA; NESTED CASE-CONTROL; DNA-REPAIR GENES AB Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (ie, radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (ie, dose-response relationships). Major conclusions of the NCRP include: 1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and 2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include 1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; 2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; 3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; 4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and 5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and C1 [Travis, Lois B.; Constine, Louis S.] Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Travis, Lois B.; Constine, Louis S.] Univ Rochester, Med Ctr, Dept Radiat Oncol, James P Wilmot Canc Ctr, Rochester, NY 14642 USA. [Ng, Andrea K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Ng, Andrea K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Allan, James M.] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Pui, Ching-Hon] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Pui, Ching-Hon] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA. [Kennedy, Ann R.] Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Xu, X. George] Rensselaer Polytech Inst, Nucl Engn & Engn Phys Program, Troy, NY USA. [Purdy, James A.] Univ Calif Davis, Dept Radiat Oncol, Davis, CA 95616 USA. [Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. [Applegate, Kimberly] Emory Univ, Dept Radiol, Atlanta, GA 30322 USA. [Gilbert, Ethel S.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Boice, John D., Jr.] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Boice, John D., Jr.] Int Epidemiol Inst, Rockville, MD USA. RP Travis, LB (reprint author), Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, James P Wilmot Canc Ctr, 265 Crittenden Blvd,CU 420318, Rochester, NY 14642 USA. EM Lois_Travis@URMC.Rochester.edu RI Allan, James/B-4448-2009 FU NCI NIH HHS [CA21765, R24 CA074206] NR 202 TC 74 Z9 75 U1 3 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD MAR PY 2012 VL 104 IS 5 BP 357 EP 370 DI 10.1093/jnci/djr533 PG 14 WC Oncology SC Oncology GA 906PH UT WOS:000301358200009 PM 22312134 ER PT J AU Sparano, JA Wang, ML Zhao, FM Stearns, V Martino, S Ligibel, JA Perez, EA Saphner, T Wolff, AC Sledge, GW Wood, WC Davidson, NE AF Sparano, Joseph A. Wang, Molin Zhao, Fengmin Stearns, Vered Martino, Silvana Ligibel, Jennifer A. Perez, Edith A. Saphner, Tom Wolff, Antonio C. Sledge, George W., Jr. Wood, William C. Davidson, Nancy E. TI Race and Hormone Receptor-Positive Breast Cancer Outcomes in a Randomized Chemotherapy Trial SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INSULIN-LIKE-GROWTH; RACIAL DISPARITIES; AFRICAN-AMERICAN; SOUTHWEST-ONCOLOGY; ESTROGEN-RECEPTOR; SURVIVAL; WOMEN; WHITE; CARCINOMA; DIAGNOSIS AB Background The association between black race and worse outcomes in operable breast cancer reported in previous studies has been attributed to a higher incidence of more aggressive triple-negative disease, disparities in care, and comorbidities. We evaluated associations between black race and outcomes, by tumor hormone receptor and HER2 expression, in patients who were treated with contemporary adjuvant therapy. Methods The effect of black race on disease-free and overall survival was evaluated using Cox proportional hazards models adjusted for multiple covariates in a clinical trial population that was treated with anthracycline- and taxane-containing chemotherapy. Categorical variables were compared using the Fisher exact test. All P values are two-sided. Results Of 4817 eligible patients, 405 (8.4%) were black. Compared with nonblack patients, black patients had a higher rate of triple-negative disease (31.9% vs 17.2%; P < .001) and a higher body mass index (median: 31.7 vs 27.4 kg/m(2); P < .001). Black race was statistically significantly associated with worse disease-free survival (5-year disease-free survival, black vs nonblack: 76.7% vs 84.5%; hazard ratio of recurrence or death = 1.58, 95% confidence interval = 1.19 to 2.10, P = .0015) and overall survival (5-year overall survival, black vs nonblack: 87.6% vs 91.9%; hazard ratio of death = 1.49, 95% confidence interval = 1.05 to 2.12, P = .025) in patients with hormone receptor-positive HER2negative disease but not in patients with triple-negative or HER2-positive disease. In a model that included black race, hormone receptor-positive HER2-negative disease vs other subtypes, and their interaction, the interaction term was statistically significant for disease-free survival (P = .027) but not for overall survival (P = .086). Conclusion Factors other than disparities in care or aggressive disease contribute to increased recurrence in black women with hormone receptor-positive breast cancer. C1 [Sparano, Joseph A.] Montefiore Med Ctr, Albert Einstein Coll Med, Weiler Div, Bronx, NY 10461 USA. [Wang, Molin; Zhao, Fengmin; Ligibel, Jennifer A.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Stearns, Vered; Wolff, Antonio C.] Johns Hopkins Univ, Kimmel Canc Ctr, Baltimore, MD USA. [Martino, Silvana] Angeles Clin, Santa Monica, CA USA. [Martino, Silvana] Res Inst, Santa Monica, CA USA. [Perez, Edith A.] Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. [Saphner, Tom] Green Bay Oncol, Green Bay, WI USA. [Sledge, George W., Jr.] Indiana Univ Sch Med, Simon Canc Ctr, Indianapolis, IN USA. [Wood, William C.] Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. [Davidson, Nancy E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Sparano, JA (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Weiler Div, 1825 Eastchester Rd,2S Rm 47, Bronx, NY 10461 USA. EM jsparano@montefiore.org OI Wolff, Antonio/0000-0003-3734-1063 FU Department of Health and Human Services; National Institutes of Health [CA14958, CA23318, CA66636, CA21115, CA32012, CA11789, CA25224, CA49883, CA16116]; Abraxis; Merck; Novartis; Pfizer; Genentech; Sanofi Oncology; GlaxoSmithKline FX Supported in part by grants from the Department of Health and Human Services and the National Institutes of Health (CA14958 to the Albert Einstein College of Medicine; CA23318 to the Eastern Cooperative Oncology Group (ECOG) statistical center; CA66636 to the ECOG data management center; CA21115 to the ECOG coordinating center and chairman's office; CA32012 to Southwest Oncology Group; CA11789 to Cancer and Leukemia Group B; CA25224 to North Central Cancer Treatment Group; CA49883 to the Indiana University School of Medicine; and CA16116 to Johns Hopkins Oncology Center).; V. Stearns has received grants or contracts from Abraxis, Merck, Novartis, and Pfizer and has received honoraria from AstraZeneca. E. A. Perez has received grants or contracts from Genentech, Sanofi Oncology, Novartis, and GlaxoSmithKline. G. W. Sledge is a paid board member of the Komen Foundation. NR 29 TC 28 Z9 28 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR PY 2012 VL 104 IS 5 BP 406 EP 414 DI 10.1093/jnci/djr543 PG 9 WC Oncology SC Oncology GA 906PH UT WOS:000301358200012 PM 22250182 ER PT J AU Kuchiba, A Morikawa, T Yamauchi, M Imamura, Y Liao, XY Chan, AT Meyerhardt, JA Giovannucci, E Fuchs, CS Ogino, S AF Kuchiba, Aya Morikawa, Teppei Yamauchi, Mai Imamura, Yu Liao, Xiaoyun Chan, Andrew T. Meyerhardt, Jeffrey A. Giovannucci, Edward Fuchs, Charles S. Ogino, Shuji TI Body Mass Index and Risk of Colorectal Cancer According to Fatty Acid Synthase Expression in the Nurses' Health Study SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; COLON-CANCER; PHYSICAL-ACTIVITY; RECTAL-CANCER; MICROSATELLITE INSTABILITY; WEIGHT CHANGE; JAPANESE MEN; LIFE-STYLE; WOMEN; SIZE AB Fatty acid synthase (FASN) plays an important role in energy metabolism of fatty acids and is overexpressed in some colon cancers. We investigated whether associations between body mass index (BMI) and risk of colorectal cancer varied according to FASN expression. During follow-up of 109 051 women in the ongoing prospective Nurses' Health Study, a total of 1351 incident colon and rectal cancers were diagnosed between 1986 and 2004. We constructed tissue microarrays of the available resected tumor samples (n = 536), and FASN expression was analyzed by immunohistochemistry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. All statistical tests were two-sided. High BMI was associated with an increased risk of FASN-negative (no or weak expression) colorectal cancer compared with normal BMI (high BMI [>= 30 kg/m(2)], ie, obese vs normal BMI [18.5-22.9 kg/m(2)], HR = 2.25, 95% CI = 1.49 to 3.40, P-trend < .001) but not with FASN-positive (moderate to strong expression) colorectal cancer. A statistically significant heterogeneity in colorectal cancer risks was observed between FASN-negative and FASN-positive tumors (P-heterogeneity = .033). The age-adjusted incidence rates for FASN-positive and FASN-negative colorectal cancers were 10.9 and 7.1, respectively, per 100000 person-years. This molecular pathological epidemiology study supports a role of energy metabolism in colorectal cancer pathogenesis. C1 [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Pathol, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, Boston, MA 02215 USA. [Kuchiba, Aya; Morikawa, Teppei; Yamauchi, Mai; Imamura, Yu; Liao, Xiaoyun; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kuchiba, Aya; Morikawa, Teppei; Yamauchi, Mai; Imamura, Yu; Liao, Xiaoyun; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chan, Andrew T.; Giovannucci, Edward; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Pathol, Dana Farber Canc Inst,Ctr Mol Oncol Pathol, 450 Brookline Ave,Rm JF-215C, Boston, MA 02215 USA. EM shuji_ogino@dfci.harvard.edu FU National Cancer Institute (NCI) at the National Institutes of Health (NIH) [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826, R01 CA151993, R01 CA137178]; Bennett Family Fund; Entertainment Industry Foundation; Japan Society for Promotion of Science FX This work was supported by the National Cancer Institute (NCI) at the National Institutes of Health (NIH) (P01 CA87969 to S. E. Hankinson; P01 CA55075 to W. C. Willett; P50 CA127003 to C.S.F.; K07 CA122826 and R01 CA151993 to S.O.; R01 CA137178 to A.T.C.), grants from the Bennett Family Fund and the Entertainment Industry Foundation through National Colorectal Cancer Research Alliance, and a fellowship grant from the Japan Society for Promotion of Science (to T.M.). NR 39 TC 35 Z9 37 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR PY 2012 VL 104 IS 5 BP 415 EP 420 DI 10.1093/jnci/djr542 PG 6 WC Oncology SC Oncology GA 906PH UT WOS:000301358200013 PM 22312135 ER PT J AU Bart, BA Goldsmith, SR Lee, KL Redfield, MM Felker, GM O'Connor, CM Chen, HH Rouleau, JL Givertz, MM Semigran, MJ Mann, D Deswal, A Bull, DA Lewinter, MM Braunwald, E AF Bart, Bradley A. Goldsmith, Steven R. Lee, Kerry L. Redfield, Margaret M. Felker, G. Michael O'Connor, Christopher M. Chen, Horng H. Rouleau, Jean L. Givertz, Michael M. Semigran, Marc J. Mann, Douglas Deswal, Anita Bull, David A. Lewinter, Martin M. Braunwald, Eugene TI Cardiorenal Rescue Study in Acute Decompensated Heart Failure: Rationale and Design of CARRESS-HF, for the Heart Failure Clinical Research Network SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Cardiorenal syndrome; congestion; diuretics; ultrafiltration; heart failure ID WORSENING RENAL-FUNCTION; EXTRACORPOREAL ULTRAFILTRATION; BODY-FLUID; RETENTION; REMOVAL; TRENDS AB Background: Worsening renal function is common among patients hospitalized for acute decompensated heart failure (ADHF). When this occurs, subsequent management decisions often pit the desire for effective decongestion against concerns about further worsening renal function. There are no evidence-based treatments or guidelines to assist in these difficult management decisions. Ultrafiltration is a potentially attractive alternative to loop diuretics for the management of fluid overload in patients with ADHF and worsening renal function. Methods and Results: The National Heart, Lung, and Blood Institute Heart Failure Clinical Research Network designed a clinical trial to determine if ultrafiltration results in improved renal function and relief of congestion compared with stepped pharmacologic care when assessed 96 hours after randomization in patients with ADHF and cardiorenal syndrome. Enrollment began in June 2008. This paper describes the rationale and design of the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF). Conclusions: Treating the signs and symptoms of congestion in ADHF is often complicated by worsening renal function. CARRESS-HF compares treatment strategies (ultrafiltration vs stepped pharmacologic care) for the management of worsening renal function in patients with ADHF. The results of the CARRESS-HF trial are expected to provide information and evidence as to the most appropriate approaches for treating this challenging patient population. (J Cardiac Fail 2012;18:176-182) C1 [Bart, Bradley A.; Goldsmith, Steven R.] Univ Minnesota, Minneapolis, MN USA. [Lee, Kerry L.] Duke Clin Res Inst, Durham, NC USA. [Redfield, Margaret M.; Chen, Horng H.] Mayo Clin, Rochester, MN USA. [Felker, G. Michael; O'Connor, Christopher M.] Duke Univ, Sch Med, Durham, NC USA. [Felker, G. Michael; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Heart Ctr, Durham, NC 27710 USA. [Rouleau, Jean L.] Univ Montreal, Montreal, PQ, Canada. [Rouleau, Jean L.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Givertz, Michael M.; Braunwald, Eugene] Brigham & Womens Hosp, Boston, MA 02115 USA. [Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mann, Douglas] Washington Univ, Sch Med, St Louis, MO USA. [Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA. [Bull, David A.] Univ Utah, Salt Lake City, UT USA. [Lewinter, Martin M.] Univ Vermont, Burlington, VT USA. RP Bart, BA (reprint author), O5 HCMC,701 Pk Ave S, Minneapolis, MN 55415 USA. EM bartx006@umn.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [U10 HL084904] NR 22 TC 36 Z9 38 U1 1 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD MAR PY 2012 VL 18 IS 3 BP 176 EP 182 DI 10.1016/j.cardfail.2011.12.009 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 910ZG UT WOS:000301686500003 PM 22385937 ER PT J AU Chang, ALS Alora-Palli, M Lima, XT Chang, TC Cheng, C Chung, CM Amir, O Kimball, AB AF Chang, Anne Lynn S. Alora-Palli, Maria Lima, Xinaida T. Chang, Tiffany C. Cheng, Carol Chung, Connie M. Amir, Omar Kimball, Alexa B. TI A Randomized, Double-Blind, Placebo-Controlled, Pilot Study to Assess the Efficacy and Safety of Clindamycin 1.2% and Tretinoin 0.025% Combination Gel for the Treatment of Acne Rosacea Over 12 Weeks SO JOURNAL OF DRUGS IN DERMATOLOGY LA English DT Article ID TOPICAL TRETINOIN; ISOTRETINOIN; THERAPY AB Background: Papulopustular acne rosacea is a chronic inflammatory condition which can be difficult to treat. Many patients are unwilling to use systemic medications, and single topical agents alone may not address all the symptoms of rosacea. A combination topical clindamycin phosphate 1.2% and tretinoin 0.025% gel is efficacious for acne vulgaris, and may be helpful for rosacea, since acne vulgaris and rosacea shares many similar clinical and histologic features. Objective: To assess the preliminary efficacy and safety of a combination gel consisting of clindamycin phosphate 1.2% and tretinoin 0.025% on papulopustular rosacea after 12 weeks of usage. Methods: Randomized, double-blind, placebo controlled two site study of 79 participants with moderate to severe papulopustular acne rosacea using both physician and subjects' validated assessment tools. Primary endpoint consisted of statistically significant reduction in absolute papule or pustule count after 12 weeks of usage. Results: There was no significant difference in papule/pustule count between placebo and treated groups after 12 weeks (P=0.10). However, there was nearly significant improvement in physicians' assessments of the telangiectasia component of rosacea (P=0.06) and erythematotelangiectatic rosacea subtype (P=0.05) in treated versus placebo group after 12 weeks. The only significant adverse event different was facial scaling, which was significantly increased in treated group (P=0.01), but this did not result in discontinuation of study drug. Conclusions: A combination gel of clindamycin phosphate 1.2% and tretinoin 0.025% may improve the telangiectatic component of rosacea and appears to better treat the erythemotelangiectatic subtype of rosacea rather than papulopustular subtype. Our preliminary study suggests that future studies with much larger sample size might confirm our findings. Clinical Trials: NCT00823901. C1 [Chang, Anne Lynn S.] Stanford Univ, Sch Med, Dept Dermatol, Redwood City, CA 94063 USA. [Alora-Palli, Maria; Lima, Xinaida T.; Cheng, Carol; Chung, Connie M.; Kimball, Alexa B.] Massachusetts Gen Hosp, Clin Unit Res Trials & Outcomes Skin CURTIS, Boston, MA 02114 USA. RP Chang, ALS (reprint author), Stanford Univ, Sch Med, Dept Dermatol, 450 Broadway St,MC 5334, Redwood City, CA 94063 USA. EM alschang@stanford.edu FU Medicis FX This study was funded by a grant from Medicis. The authors have no conflict of interest to disclose. This work was accepted as a poster abstract to the 2011 Summer American Academy of Dermatology meeting. NR 15 TC 7 Z9 7 U1 0 U2 0 PU JOURNAL OF DRUGS IN DERMATOLOGY PI NEW YORK PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA SN 1545-9616 J9 J DRUGS DERMATOL JI J. Drugs Dermatol. PD MAR PY 2012 VL 11 IS 3 BP 333 EP 339 PG 7 WC Dermatology SC Dermatology GA 905ZU UT WOS:000301315500006 PM 22395584 ER PT J AU Lenehan, G AF Lenehan, Gail TI IS YOUR WORKPLACE A PPE? SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Lenehan, Gail] Massachusetts Gen Hosp, Emergency Dept, Boston, MA 02114 USA. EM gail.lenehan@gmail.com NR 2 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 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD MAR PY 2012 VL 38 IS 2 BP 113 EP 114 DI 10.1016/j.jen.2012.01.009 PG 2 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 914WT UT WOS:000301984500001 PM 22401609 ER PT J AU Zhou, W Russell, CW Johnson, KL Mortensen, RD Erickson, DL AF Zhou, Wei Russell, Colin W. Johnson, Kody L. Mortensen, Richard D. Erickson, David L. TI Gene Expression Analysis of Xenopsylla cheopis (Siphonaptera: Pulicidae) Suggests a Role for Reactive Oxygen Species in Response to Yersinia pestis Infection SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Xenopsylla cheopis; Yersinia pestis transmission; reactive oxygen species; flea gene expression ID EARLY-PHASE TRANSMISSION; PHOSPHOLIPASE A(2); UNBLOCKED FLEAS; DROSOPHILA GUT; DUAL OXIDASE; IMMUNITY; VECTOR; PLAGUE; EVOLUTION; PHAGOCYTOSIS AB Fleas are vectors for a number of pathogens including Yersinia pestis, yet factors that govern interactions between fleas and Y. pestis are not well understood. Examining gene expression changes in infected fleas could reveal pathways that affect Y. pestis survival in fleas and subsequent transmission. We used suppression subtractive hybridization to identify genes that are induced in Xenopsylla cheopis (Rothschild) (Siphonaptera: Pulicidae) in response to oral or hemocoel infection with Y. pestis. Overall, the transcriptional changes we detected were very limited. We identified several genes that are likely involved in the production or removal of reactive oxygen species (ROS). Midgut ROS levels were higher in infected fleas and antioxidant treatment before infection reduced ROS levels and resulted in higher bacterial loads. An ROS-sensitive mutant strain of Y. pestis lacking the OxyR transcriptional regulator showed reduced growth early after infection. Our results indicate that ROS may limit Y. pestis early colonization of fleas and that bacterial strategies to overcome ROS may enhance transmission. C1 [Zhou, Wei; Erickson, David L.] Brigham Young Univ, Dept Microbiol & Mol Biol, Provo, UT 84602 USA. [Johnson, Kody L.] Yale Univ, Sch Dept Immunobiol, Anlyan Ctr, New Haven, CT 06519 USA. [Mortensen, Richard D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Erickson, DL (reprint author), Brigham Young Univ, Dept Microbiol & Mol Biol, WIDB 893, Provo, UT 84602 USA. EM david_erickson@byu.edu OI Russell, Colin/0000-0003-3942-0996 FU Office of Creative and Research Activities of Brigham Young University FX We thank Bria Bird for assistance in insect rearing. This work was generously supported through a Mentoring Environment Grant from the Office of Creative and Research Activities of Brigham Young University. NR 32 TC 6 Z9 6 U1 2 U2 13 PU ENTOMOLOGICAL SOC AMER PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD MAR PY 2012 VL 49 IS 2 BP 364 EP 370 DI 10.1603/ME11172 PG 7 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 907VE UT WOS:000301446400019 PM 22493856 ER PT J AU Wang, X Cui, L Joseph, J Jiang, BB Pimental, D Handy, DE Liao, RL Loscalzo, J AF Wang, Xu Cui, Lei Joseph, Jacob Jiang, Bingbing Pimental, David Handy, Diane E. Liao, Ronglih Loscalzo, Joseph TI Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Homocysteine; Hyperhomocysteinemia; Cardiomyocytes; Contractility; Apoptosis; Antioxidant; Ischemia reperfusion injury; Oxidative stress ID CYSTATHIONINE BETA-SYNTHASE; ACTIVATED PROTEIN-KINASE; SMOOTH-MUSCLE-CELLS; RISK-FACTOR; MYOCARDIAL-INFARCTION; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; OXIDATIVE STRESS; NITRIC-OXIDE; HYPERHOMOCYSTEINEMIA LEADS AB Elevated plasma homocysteine (Hey) is a risk factor for cardiovascular disease. While Hey has been shown to promote endothelial dysfunction by decreasing the bioavailability of nitric oxide and increasing oxidative stress in the vasculature, the effects of Hey on cardiomyocytes remain less understood. In this study we explored the effects of hyperhomocysteinemia (HHcy) on myocardial function ex vivo and examined the direct effects of Hey on cardiomyocyte function and survival in vitro. Studies with isolated hearts from wild type and HHcy mice (heterozygous cystathionine-beta synthase deficient mice) demonstrated that HHcy mouse hearts had more severely impaired cardiac relaxation and contractile function and increased cell death following ischemia reperfusion (I/R). In isolated cultured adult rat ventricular myocytes, exposure to Hey for 24 h impaired cardiomyocyte contractility in a concentration-dependent manner, and promoted apoptosis as revealed by terminal dUTP nick-end labeling and cleaved caspase-3 immunoblotting. These effects were associated with activation of p38 MAPK, decreased expression of thioredoxin (TRX) protein, and increased production of reactive oxygen species (ROS). Inhibition of p38 MAPK by the selective inhibitor SB203580 (5 mu M) prevented all of these Hcy-induced changes. Furthermore, adenovirus-mediated overexpression of TRX in cardiomyocytes significantly attenuated Hcy-induced ROS generation, apoptosis, and impairment of myocyte contractility. Thus, Hey may increase the risk for CVD not only by causing endothelial dysfunction, but also by directly exerting detrimental effects on cardiomyocytes. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Loscalzo, Joseph] Harvard Univ, Dept Med, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Wang, Xu; Joseph, Jacob; Jiang, Bingbing; Handy, Diane E.; Liao, Ronglih; Loscalzo, Joseph] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wang, Xu; Cui, Lei; Pimental, David] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. [Wang, Xu; Cui, Lei; Pimental, David] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Joseph, Jacob] VA Boston Healthcare Syst, Dept Med, Boston, MA 02132 USA. RP Loscalzo, J (reprint author), Harvard Univ, Dept Med, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM jloscalzo@partners.org FU National Institutes of Health [HL089734, HL061795, HL070819, HL048743, HL107192, HL108630] FX We thank Dr. Bo Wang, Christopher E. Mahoney, Laura (Coleman) Anderson, and J.D. Galbraith for excellent technical support. Xu Wang performed the research, designed the research study, analyzed the data, and wrote the paper; Lei Cui performed the research; Jacob Joseph analyzed the data and contributed to writing the paper; Bingbing Jiang analyzed the data and contributed to writing the paper; David Pimental contributed essential regents or tools; Diane E. Handy contributed essential regents or tools and analyzed the data; Ronglih Liao designed the research study, contributed essential regents or tools and analyzed the data; and Joseph Loscalzo designed the research study, contributed essential regents or tools, analyzed the data, and contributed to writing the paper. This work was supported in part by funding from National Institutes of Health Grants: HL089734 awarded to Dr. Joseph, and HL061795, HL070819, HL048743, HL107192 and HL108630 awarded to Dr. Loscalzo. NR 48 TC 36 Z9 42 U1 0 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAR PY 2012 VL 52 IS 3 BP 753 EP 760 DI 10.1016/j.yjmcc.2011.12.009 PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 910EW UT WOS:000301621000027 PM 22227328 ER PT J AU Notrica, DM Garcia-Filion, P Moore, FO Goslar, PW Coimbra, R Velmahos, G Stevens, LR Petersen, SR Brown, CVR Foulkrod, KH Coopwood, TB Lottenberg, L Phelan, HA Bruns, B Sherck, JP Norwood, SH Barnes, SL Matthews, MR Hoff, WS deMoya, MA Bansal, V Hu, CKC Karmy-Jones, RC Vinces, F Hill, J Pembaur, K Haan, JM AF Notrica, David M. Garcia-Filion, Pamela Moore, Forrest O. Goslar, Pamela W. Coimbra, Raul Velmahos, George Stevens, Lily R. Petersen, Scott R. Brown, Carlos V. R. Foulkrod, Kelli H. Coopwood, Thomas B., Jr. Lottenberg, Lawrence Phelan, Herb A. Bruns, Brandon Sherck, John P. Norwood, Scott H. Barnes, Stephen L. Matthews, Marc R. Hoff, William S. deMoya, Marc A. Bansal, Vishal Hu, Charles K. C. Karmy-Jones, Riyad C. Vinces, Fausto Hill, Jenessa Pembaur, Karl Haan, James M. TI Management of pediatric occult pneumothorax in blunt trauma: a subgroup analysis of the American Association for the Surgery of Trauma multicenter prospective observational study SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Pneumothorax; Occult pneumothorax; Pediatric trauma; Chest tube thoracostomy; Rib fractures; Positive pressure ventilation ID TUBE THORACOSTOMY; HEMOTHORAX; CT AB Background: Occult pneumothorax (OPTX) represents air within the pleural space not visible on conventional chest radiographs. Increased use of computed tomography has led to a rise in the detection of OPTX. Optimal management remains undefined. Methods: A pediatric subgroup analysis (age <18 years) from a multicenter, observational study evaluating OPTX management. Data analyzed were pneumothorax size, management outcome, and associated risk factors to characterize those that may be safely observed. Results: Fifty-two OPTX (7.3 +/- 6.2 mm) in 51 patients were identified. None were greater than 27 mm; all those under 16.5 mm (n = 48) were successfully managed without intervention. Two patients underwent initial tube thoracostomy (one [21 mm] and the other with bilateral OPTX [24 mm, 27 mm]). Among patients under observation (n = 49), OPTX size progressed in 2; one (6.4mm) required no treatment, while one (16.5 mm) received elective intervention. Respiratory distress occurred in one patient (10.7 mm) who did not require tube thoracostomy. Nine received positive pressure ventilation; 8 did not have a tube thoracostomy. Twenty-four patients (51%) had one or more rib fractures; 3 required tube thoracostomy. Conclusion: No pediatric OPTX initially observed developed a tension pneumothorax or adverse event related to observation. Pediatric patients with OPTX less than 16 mm may be safely observed. Neither the presence of rib fractures nor need for PPV alone necessitates intervention. (C) 2012 Elsevier Inc. All rights reserved. C1 [Notrica, David M.; Garcia-Filion, Pamela; Hill, Jenessa] Phoenix Childrens Hosp, Phoenix, AZ USA. [Moore, Forrest O.; Goslar, Pamela W.; Stevens, Lily R.; Petersen, Scott R.] St Josephs Hosp, Phoenix, AZ USA. [Coimbra, Raul; Bansal, Vishal] UCSD Med Ctr, San Diego, CA USA. [Velmahos, George; deMoya, Marc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brown, Carlos V. R.; Foulkrod, Kelli H.; Coopwood, Thomas B., Jr.] Univ Med Ctr Brackenridge, Austin, TX USA. [Lottenberg, Lawrence] Univ Florida, Hlth Sci Ctr, Gainesville, FL USA. [Phelan, Herb A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Bruns, Brandon] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Sherck, John P.] Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. [Norwood, Scott H.] E Texas Med Ctr, Tyler, TX USA. [Barnes, Stephen L.] Univ Missouri, Columbia, MO USA. [Matthews, Marc R.] Maricopa Cty Gen Hosp, Phoenix, AZ USA. [Hoff, William S.] St Lukes Hosp & Med Ctr, Phoenix, AZ USA. [Hu, Charles K. C.] Scottsdale Osborne Med Ctr, Scottsdale, AZ USA. [Karmy-Jones, Riyad C.] SW Washington Med Ctr, Washington, DC USA. RP Notrica, DM (reprint author), Phoenix Childrens Hosp, Phoenix, AZ USA. EM dnotrica@phoenixchildrens.com RI Notrica, David/D-4616-2014 OI Notrica, David/0000-0002-2939-1119 NR 23 TC 8 Z9 8 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD MAR PY 2012 VL 47 IS 3 BP 467 EP 472 DI 10.1016/j.jpedsurg.2011.09.037 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 909VL UT WOS:000301593700013 PM 22424339 ER PT J AU Maguen, S Luxton, DD Skopp, NA Madden, E AF Maguen, Shira Luxton, David D. Skopp, Nancy A. Madden, Erin TI Gender differences in traumatic experiences and mental health in active duty soldiers redeployed from Iraq and Afghanistan SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Military; Women; Combat; Posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ASSAULT; GULF-WAR; MILITARY; VETERANS; CARE; COMBAT; DEPRESSION; WOMEN; PTSD AB The purpose of this study was to examine gender differences in combat exposure, military sexual trauma (MST), and their associations with mental health screen results among military personnel deployed in support of the wars in Afghanistan and Iraq. Data were collected as part of a pre- and post-deployment screening program at a large Army medical treatment facility. Cases included 7251 active duty soldiers (6697 men and 554 women) who presented for their pre- and post-deployment screening from March 2006 to July 2009. Pre-deployment mental health symptoms were statistically controlled for in our analyses. We found significant gender differences in demographic variables, exposure to combat, and MST. Women reported greater exposure to MST than did men. Although men reported greater exposure to high-intensity combat experiences than women, results indicate that women are experiencing combat at higher rates than observed in prior cohorts. Men were more likely to report problem drinking, and women were more likely to report depression symptoms. There were no gender differences with respect to PTSD symptoms. Although we found few differences between women and men in the impact of combat stressors on mental health, there was a stronger association between injury and PTSD symptoms for women than for men. Our findings indicate that it would be useful for clinicians to be aware of this difference and assess for exposure to a full range of traumatic combat experiences, particularly injury, as not all types of combat experiences may be equally experienced by men and women returning from military deployments. Published by Elsevier Ltd. C1 [Maguen, Shira] San Francisco VA Med Ctr, PTSD Program 116P, San Francisco, CA 94121 USA. [Maguen, Shira] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94122 USA. [Luxton, David D.; Skopp, Nancy A.] OMAMC, Def Ctr Excellence Psychol Hlth, Natl Ctr Telehealtl & Technol, Tacoma, WA 98431 USA. [Luxton, David D.; Skopp, Nancy A.] OMAMC, Def Ctr Traumat Brain Injury, Tacoma, WA 98431 USA. [Luxton, David D.; Skopp, Nancy A.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, PTSD Program 116P, 4150 Clement St, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov RI Schueter, nicos/A-3625-2014 FU VA Health Services Research and Development (HSRD) FX This study was funded by a VA Health Services Research and Development (HSR&D) Career Development Award (Maguen). VA HSR&D had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 29 TC 52 Z9 52 U1 2 U2 22 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAR PY 2012 VL 46 IS 3 BP 311 EP 316 DI 10.1016/j.jpsychires.2011.11.007 PG 6 WC Psychiatry SC Psychiatry GA 911YJ UT WOS:000301760300006 PM 22172997 ER PT J AU Targum, SD Hassman, H Pinho, M Fava, M AF Targum, Steven D. Hassman, Howard Pinho, Maria Fava, Maurizio TI Development of a clinical global impression scale for fatigue SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Reliability; Validity; Global assessment; Fatigue ID MAJOR DEPRESSIVE DISORDER; DOUBLE-BLIND; SYMPTOMS; VALIDITY; SCHIZOPHRENIA; RELIABILITY AB Physical, cognitive, and affective components of fatigue are often associated with depression and other Axis I psychiatric disorders. We developed two, single item global assessment scales to specifically evaluate symptoms of fatigue. 101 subjects visiting a clinical trial site consented to participate in this reliability and validity study. Diagnoses included Major Depressive Disorder, Bipolar disorder, and schizophrenia. There were two clinic visits during which the modified Clinician and Patient Impressions of Fatigue rating instruments were administered in conjunction with the MGH cognitive and physical functioning questionnaire (MGH-CPFQ), a validated patient-rated 7-item scale. CGI-Severity and PGI-Severity for fatigue were well correlated at two separate visits (p < 0.00005). At visit 1, the mean CGI-S for fatigue was 3.33 +/- 1.53 (SD) and the PGI-S for fatigue was 3.57 +/- 1.70 (r = 0.75; p = 0.000). At visit 1, the total MGH-CPFQ was 21.66 +/- 6.92. Both CGI-S and PGI-S measures for fatigue were highly correlated with the MGH-CPFQ: CGI-S (r = 076; p < 0.00005); PGI-S (r = 0.62; p < 0.00005). Both the PGI-S and CGI-S for fatigue revealed temporal stability and convergent validity for the MGH-CPFQ (r = 0.83 for CGI-S and 0.73 for PGI-S). There was high internal consistency between the two independent CGI raters at visit 2 as demonstrated by a kappa statistic = 0.971 (CGI-S) and 0.868 (CGI-I) and Cronbach's alpha = 0.998 (CGI-S) and 0.941 (CGI-I). As shown here, the modified CGI and PGI instruments for fatigue are reliable measures of fatigue and both measures are validated with the MGH-CPFQ instrument. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Targum, Steven D.] Clintara LLC, Boston, MA 02116 USA. [Hassman, Howard; Pinho, Maria] CRI Worldwide, Willingboro, NJ USA. [Fava, Maurizio] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Targum, SD (reprint author), Clintara LLC, 505 Tremont St 907, Boston, MA 02116 USA. EM sdtargum@yahoo.com FU Clintara LLC; Canton MA; CRI Worldwide; Willingboro NJ FX Partial support for this research project came from Clintara LLC, Canton MA and CRI Worldwide, Willingboro NJ. NR 23 TC 7 Z9 7 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD MAR PY 2012 VL 46 IS 3 BP 370 EP 374 DI 10.1016/j.jpsychires.2011.12.001 PG 5 WC Psychiatry SC Psychiatry GA 911YJ UT WOS:000301760300014 PM 22236834 ER PT J AU Rubinsky, AD Sun, H Blough, DK Maynard, C Bryson, CL Harris, AH Hawkins, EJ Beste, LA Henderson, WG Hawn, MT Hughes, G Bishop, MJ Etzioni, R Tonnesen, H Kivlahan, DR Bradley, KA AF Rubinsky, Anna D. Sun, Haili Blough, David K. Maynard, Charles Bryson, Christopher L. Harris, Alex H. Hawkins, Eric J. Beste, Lauren A. Henderson, William G. Hawn, Mary T. Hughes, Grant Bishop, Michael J. Etzioni, Ruth Tonnesen, Hanne Kivlahan, Daniel R. Bradley, Katharine A. TI AUDIT-C Alcohol Screening Results and Postoperative Inpatient Health Care Use SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID LENGTH-OF-STAY; QUALITY IMPROVEMENT PROGRAM; INTENSIVE-CARE; ELECTIVE SURGERY; USE DISORDERS; RISK-FACTORS; MORBIDITY; VETERANS; MEN; COMPLICATIONS AB BACKGROUND: Alcohol screening scores >= 5 on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) up to a year before surgery have been associated with postoperative complications, but the association with postoperative health care use is unknown. This study evaluated whether AUDIT-C scores in the year before surgery were associated with postoperative hospital length of stay, total ICU days, return to the operating room, and hospital readmission. STUDY DESIGN: This cohort study included male Veterans Affairs patients who completed the AUDIT-C on mailed surveys (October 2003 through September 2006) and were hospitalized for nonemergent noncardiac major operations in the following year. Postoperative health care use was evaluated across 4 AUDIT-C risk groups (scores 0, 1 to 4, 5 to 8, and 9 to 12) using linear or logistic regression models adjusted for sociodemographics, smoking status, surgical category, relative value unit, and time from AUDIT-C to surgery. Patients with AUDIT-C scores indicating low-risk drinking (scores 1 to 4) were the referent group. RESULTS: Adjusted analyses revealed that among eligible surgical patients (n = 5,171), those with the highest AUDIT-C scores (ie, 9 to 12) had longer postoperative hospital length of stay (5.8 [95% CI, 5.0 - 6.7] vs 5.0 [95% CI, 4.7 - 5.3] days), more ICU days (4.5 [95% CI, 3.- - 5.8] vs 2.8 [95% CI, 2.6 - 3.1] days), and increased probability of return to the operating room (10% [95% CI, 6 - 13%] vs 5% [95% CI, 4 - 6%]) in the 30 days after surgery, but not increased hospital readmission within 30 days postdischarge, relative to the low-risk group. CONCLUSIONS: AUDIT-C screening results could be used to identify patients at risk for increased postoperative health care use who might benefit from preoperative alcohol interventions. (J Am Coll Surg 2012; 214: 296-305. c 2012 by the American College of Surgeons) C1 [Rubinsky, Anna D.; Maynard, Charles; Etzioni, Ruth; Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Blough, David K.] Univ Washington, Dept Pharm, Seattle, WA 98195 USA. [Hawkins, Eric J.; Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Bishop, Michael J.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. [Etzioni, Ruth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Etzioni, Ruth] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA. [Harris, Alex H.] Ctr Hlth Care Evaluat, Dept Vet Affairs Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Henderson, William G.; Hughes, Grant] Dept Vet Affairs Eastern Colorado Healthcare Syst, Denver, CO USA. [Henderson, William G.] Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. [Hawn, Mary T.] Birmingham Vet Affairs Med Ctr, C SMART, Birmingham, W Midlands, England. [Hawn, Mary T.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Tonnesen, Hanne] Bispebjerg Hosp, WHO Collaborating Ctr Evidence Based Hlth Promot, Copenhagen, Denmark. RP Rubinsky, AD (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, 1660 S Columbian Way,S 152, Seattle, WA 98108 USA. EM Anna.Rubinsky@va.gov RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU Department of Veterans Affairs; Veterans Health Administration; Office of Research and Development and Health Services Research and Development [IAC 06-021]; Agency for Healthcare Research and Quality Institutional National Research Service through University of Washington [T32 HS 013853] FX The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health Services Research and Development (IAC 06-021). Ms Rubinsky was also supported by an Agency for Healthcare Research and Quality Institutional National Research Service Award through the University of Washington (T32 HS 013853) when this work was conducted. NR 49 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAR PY 2012 VL 214 IS 3 BP 296 EP U69 DI 10.1016/j.jamcollsurg.2011.11.007 PG 11 WC Surgery SC Surgery GA 912BS UT WOS:000301770100008 PM 22244208 ER PT J AU Kerfoot, BP Baker, H AF Kerfoot, B. Price Baker, Harley TI An Online Spaced-Education Game to Teach and Assess Residents: A Multi-Institutional Prospective Trial SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; FINANCIAL INCENTIVES; IMPROVES; CANCER AB BACKGROUND: While games are frequently used in resident education, there is little evidence supporting their efficacy. We investigated whether a spaced-education (SE) game can be both a reliable and valid method of assessing residents' knowledge and an effective means of teaching core content. STUDY DESIGN: The SE game consisted of 100 validated multiple-choice questions and explanations on core urology content. Residents were sent 2 questions each day via email. Adaptive game mechanics re-sent the questions in 2 or 6 weeks if answered incorrectly and correctly, respectively. Questions expired if not answered on time (appointment dynamic). Residents retired questions by answering each correctly twice in a row (progression dynamic). Competition was fostered by posting relative performance amongresidents. Main outcomes measures were baseline scores (percentage of questions answered correctly on initial presentation) and completion scores (percentage of questions retired). RESULTS: Nine hundred thirty-one US and Canadian residents enrolled in the 45-week trial. Cronbach alpha reliability for the SE baseline scores was 0.87. Baseline scores (median 62%, interquartile range [IQR] 17%) correlated with scores on the 2008 American Urological Association in-service examination (ISE08), 2009 American Board of Urology qualifying examination (QE09), and ISE09 (r = 0.76, 0.46, and 0.64, respectively; all p < 0.001). Baseline scores varied by sex, country, medical degree, and year of training (all p <= 0.001). Completion scores (median 100%, IQR 2%) correlated with ISE08 and ISE09 scores (r = 0.35, p < 0.001 for both). Seventy-two percent of enrollees (667 of 931) requested to participate in future SE games. CONCLUSIONS: An SE game is a reliable and valid means to assess residents' knowledge and is a well-accepted method by which residents can master core content. (J Am Coll Surg 2012;214:367-373. (C) 2012 by the American College of Surgeons) C1 [Kerfoot, B. Price] Vet Affairs Boston Healthcare Syst, Surg Serv, Urol Sect, Boston, MA USA. [Kerfoot, B. Price] Harvard Univ, Sch Med, Boston, MA USA. [Baker, Harley] Calif State Univ, Camarillo, CA USA. RP Kerfoot, BP (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave,151DIA, Jamaica Plain, MA 02130 USA. EM price.kerfoot@gmail.com FU American Urological Association (Linthicum, MD); American Urological Association Foundation (Linthicum, MD); Astellas Pharma US, Inc; United States Agency for Healthcare Research and Quality FX Supported in part by the American Urological Association (Linthicum, MD), the American Urological Association Foundation (Linthicum, MD), Astellas Pharma US, Inc, and the United States Agency for Healthcare Research and Quality. NR 23 TC 16 Z9 16 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAR PY 2012 VL 214 IS 3 BP 367 EP 373 DI 10.1016/j.jamcollsurg.2011.11.009 PG 7 WC Surgery SC Surgery GA 912BS UT WOS:000301770100015 PM 22225647 ER PT J AU Li, YN Radner, S French, MM Pinzon-Duarte, G Daly, GH Burgeson, RE Koch, M Brunken, WJ AF Li, Yong N. Radner, Stephanie French, Margaret M. Pinzon-Duarte, German Daly, Gerard H. Burgeson, Robert E. Koch, Manuel Brunken, William J. TI The gamma 3 chain of laminin is widely but differentially expressed in murine basement membranes: Expression and functional studies SO MATRIX BIOLOGY LA English DT Article DE Laminin; Retina; CNS; Cerebellum; Angiogenesis; Kidney; Testis ID CELL PRECURSOR PROLIFERATION; INTEGRIN-LINKED KINASE; MOUSE RETINA; ECTOPLASMIC SPECIALIZATION; CEREBELLAR DEVELOPMENT; RODENT RETINA; GENE; ISOFORMS; ABSENCE; NEURONS AB Laminins are heterotrimeric extracellular glycoproteins found in, but not confined to, basement membranes (BMs). They are important components in formation of the molecular networks of BMs as well as in cell polarity, cell differentiation and tissue morphogenesis. Each laminin is composed by an alpha, a beta and a gamma chain. Previous studies have shown that the gamma 3 chain is partnered with either the beta 1 chain (in placenta) or beta 2 chain (in the CNS) (Libby et al., 2000). Several studies, including our own, suggested that the gamma 3 chain is expressed in both apical and basal compartments (Koch et al., 1999; Gersdorff et al., 2005; Van and Cheng, 2006). This study investigates the expression pattern of the gamma 3 chain in mouse. We developed three new gamma 3-reactive antibodies, and we show that the gamma 3 chain is present in BMs. The distribution pattern is considerably more restricted than that of the gamma 1 chain and within any tissue there is differential deposition into BM compartments. This is particularly true in the retina and brain, where gamma 3 is uniquely expressed in a subset of the vascular basement membranes and the pial surface. We used conventional genetic ablation techniques to remove the gamma 3 chain in mice; unlike other laminin null mice (alpha 5, beta 2, gamma 1 nulls), these mice live a normal lifespan and have only minor abnormalities, the most striking of which are ectopic granule cells in the cerebellum and an apparent increase in capillary branching in the outer retina. These data support the suggestion that the gamma 3 chain is deposited in BMs and contributes some unique properties to their function, particularly in the nervous system. (c) 2011 Elsevier B.V. All rights reserved. C1 [Pinzon-Duarte, German; Brunken, William J.] Suny Downstate Med Ctr, Dept Ophthalmol, Brooklyn, NY 11203 USA. [Pinzon-Duarte, German; Brunken, William J.] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA. [Pinzon-Duarte, German; Brunken, William J.] Suny Downstate Med Ctr, SUNY Eye Inst, Brooklyn, NY 11203 USA. [Li, Yong N.; Radner, Stephanie; Daly, Gerard H.; Brunken, William J.] Tufts Univ, Sch Med, Sackler Sch Biomed Sci, Boston, MA 02111 USA. [French, Margaret M.; Burgeson, Robert E.; Koch, Manuel; Brunken, William J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Koch, Manuel] Univ Cologne, Inst Oral & Musculoskeletal Biol, Ctr Biochem, D-50931 Cologne, Germany. [Koch, Manuel] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany. RP Brunken, WJ (reprint author), Suny Downstate Med Ctr, Dept Ophthalmol, 450 Clarkson Ave,Box 5, Brooklyn, NY 11203 USA. EM william.brunken@downstate.edu OI Brunken, William J/0000-0001-7330-1814 FU NEI NIH HHS [R01 EY012676-11, R01 EY012676-08, R01 EY012676-09, R01 EY012676, EY 12767, R01 EY012676-10A2]; NINDS NIH HHS [NS 39502, R01 NS039502-03, R01 NS039502, R01 NS039502-04] NR 50 TC 9 Z9 9 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD MAR PY 2012 VL 31 IS 2 BP 120 EP 134 DI 10.1016/j.matbio.2011.12.002 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 910JL UT WOS:000301632900006 PM 22222602 ER PT J AU Kee, Y Huang, M Chang, S Moreau, LA Park, E Smith, PG D'Andrea, AD AF Kee, Younghoon Huang, Min Chang, Sophia Moreau, Lisa A. Park, Eunmi Smith, Peter G. D'Andrea, Alan D. TI Inhibition of the Nedd8 System Sensitizes Cells to DNA Interstrand Cross-linking Agents SO MOLECULAR CANCER RESEARCH LA English DT Article ID FANCONI-ANEMIA PATHWAY; MULTIPLE-MYELOMA CELLS; DAMAGE RESPONSE; S-PHASE; FANCD2 MONOUBIQUITINATION; NEDD8-ACTIVATING ENZYME; RE-REPLICATION; OVARIAN-CANCER; CDT1; REPAIR AB The Fanconi anemia pathway is required for repair of DNA interstrand cross-links (ICL). Fanconi anemia pathway-deficient cells are hypersensitive to DNA ICL-inducing drugs such as cisplatin. Conversely, hyperactivation of the Fanconi anemia pathway is a mechanism that may underlie cellular resistance to DNA ICL agents. Modulating FANCD2 monoubiquitination, a key step in the Fanconi anemia pathway, may be an effective therapeutic approach to conferring cellular sensitivity to ICL agents. Here, we show that inhibition of the Nedd8 conjugation system increases cellular sensitivity to DNA ICL-inducing agents. Mechanistically, the Nedd8 inhibition, either by siRNA-mediated knockdown of Nedd8-conjugating enzymes or treatment with a Nedd8-activating enzyme inhibitor MLN4924, suppressed DNA damage-induced FANCD2 monoubiquitination and CHK1 phosphorylation. Our data indicate that inhibition of the Fanconi anemia pathway is largely responsible for the heightened cellular sensitivity to DNA ICLs upon Nedd8 inhibition. These results suggest that a combination of Nedd8 inhibition with ICL-inducing agents may be an effective strategy for sensitizing a subset of drug-resistant cancer cells. Mol Cancer Res; 10(3); 369-77. (C)2012 AACR. C1 [Kee, Younghoon; Chang, Sophia] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA. [Huang, Min; Moreau, Lisa A.; Park, Eunmi; D'Andrea, Alan D.] Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Sch Med,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. [Smith, Peter G.] Millennium Pharmaceut Inc, Cambridge, MA USA. RP Kee, Y (reprint author), 4202 E Fowler Ave,BSF216, Tampa, FL 33620 USA. EM Ykee@usf.edu; Alan_Dandrea@dfci.harvard.edu OI huang, min/0000-0001-6735-1612 FU NIH [5R01DK43889, 5R37HL52725]; Leukemia and Lymphoma Society FX This work was supported by NIH grants 5R01DK43889 and 5R37HL52725 to A. D. D'Andrea and departmental startup funds to Y. Kee. Y. Kee was a recipient of a Leukemia and Lymphoma Society Career Development Fellowship. NR 38 TC 34 Z9 34 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAR PY 2012 VL 10 IS 3 BP 369 EP 377 DI 10.1158/1541-7786.MCR-11-0497 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 912EO UT WOS:000301777700010 PM 22219386 ER PT J AU Leoni, V Strittmatter, L Zorzi, G Zibordi, F Dusi, S Garavaglia, B Venco, P Caccia, C Souza, AL Deik, A Clish, CB Rimoldi, M Ciusani, E Bertini, E Nardocci, N Mootha, VK Tiranti, V AF Leoni, Valerio Strittmatter, Laura Zorzi, Giovanna Zibordi, Federica Dusi, Sabrina Garavaglia, Barbara Venco, Paola Caccia, Claudio Souza, Amanda L. Deik, Amy Clish, Clary B. Rimoldi, Marco Ciusani, Emilio Bertini, Enrico Nardocci, Nardo Mootha, Vamsi K. Tiranti, Valeria TI Metabolic consequences of mitochondrial coenzyme A deficiency in patients with PANK2 mutations SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE PKAN; Coenzyme A; Mitochondria; Metabolomics; Cholesterol ID BRAIN IRON ACCUMULATION; KINASE-ASSOCIATED NEURODEGENERATION; HUNTINGTONS-DISEASE; BILE-ACIDS; CHOLESTEROL-METABOLISM; BIOSYNTHETIC-PATHWAY; NERVOUS-SYSTEM; 24S-HYDROXYCHOLESTEROL; DYSFUNCTION; MANIFEST AB Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, inborn error of metabolism characterized by iron accumulation in the basal ganglia and by the presence of dystonia, dysarthria, and retinal degeneration. Mutations in pantothenate kinase 2 (PANK2), the rate-limiting enzyme in mitochondrial coenzyme A biosynthesis, represent the most common genetic cause of this disorder. How mutations in this core metabolic enzyme give rise to such a broad clinical spectrum of pathology remains a mystery. To systematically explore its pathogenesis, we performed global metabolic profiling on plasma from a cohort of 14 genetically defined patients and 18 controls. Notably, lactate is elevated in PKAN patients, suggesting dysfunctional mitochondria] metabolism. As predicted, but never previously reported, pantothenate levels are higher in patients with premature stop mutations in PANK2. Global metabolic profiling and follow-up studies in patient-derived fibroblasts also reveal defects in bile acid conjugation and lipid metabolism, pathways that require coenzyme A. These findings raise a novel therapeutic hypothesis, namely, that dietary fats and bile acid supplements may hold potential as disease-modifying interventions. Our study illustrates the value of metabolic profiling as a tool for systematically exploring the biochemical basis of inherited metabolic diseases. (C) 2011 Elsevier Inc. All rights reserved. C1 [Dusi, Sabrina; Garavaglia, Barbara; Venco, Paola; Tiranti, Valeria] IRCCS Fdn, Unit Mol Neurogenet, Pierfranco & Luisa Mariani Ctr Study Mitochondria, Neurol Inst C Besta, I-20126 Milan, Italy. [Leoni, Valerio; Caccia, Claudio; Rimoldi, Marco; Ciusani, Emilio] IRCCS Fdn, Lab Clin Pathol & Med Genet, Neurol Inst C Besta, I-20126 Milan, Italy. [Strittmatter, Laura; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. [Strittmatter, Laura; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Strittmatter, Laura; Mootha, Vamsi K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Strittmatter, Laura; Souza, Amanda L.; Deik, Amy; Clish, Clary B.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA. [Zorzi, Giovanna; Zibordi, Federica; Nardocci, Nardo] IRCCS Fdn, Unit Child Neurol, Neurol Inst C Besta, I-20126 Milan, Italy. [Bertini, Enrico] Bambino Gesu Pediat Res Hosp, Mol Med Unit, Dept Neurosci, Rome, Italy. RP Tiranti, V (reprint author), IRCCS Fdn, Unit Mol Neurogenet, Pierfranco & Luisa Mariani Ctr Study Mitochondria, Neurol Inst C Besta, Via Temolo 4, I-20126 Milan, Italy. EM tiranti@istituto-besta.it RI Tiranti, Valeria/J-8233-2016; OI Tiranti, Valeria/0000-0002-3584-7338; Bertini, Enrico/0000-0001-9276-4590 FU Mariani Foundation of Milan [R-10-84]; Italian Foundation AISNAF (Associazione Italiana Sindromi Neurodegenerative Accumulo di Ferro); Italian Minister of Health, Fondi per giovani Ricercatori; DNA bank [GTB07001]; Bank for the Diagnosis and Research of Movement Disorders (MDB) of the EuroBiobank; National Science Foundation [DGE - 0644491]; Broad Institute Scientific Planning and Allocation of Resources Committee; Nestle Research Center to the Broad Institute [R01DK081457]; National Institutes of Health; Fondazione Telethon NR 44 TC 41 Z9 41 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2012 VL 105 IS 3 BP 463 EP 471 DI 10.1016/j.ymgme.2011.12.005 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 913VV UT WOS:000301906400173 PM 22221393 ER PT J AU Ben Sassi, S Nabli, F Hentati, E Nahdi, H Trabelsi, M Ben Ayed, H Amouri, R Duda, JE Farrer, MJ Hentati, F AF Ben Sassi, Samia Nabli, Fatma Hentati, Emna Nahdi, Houda Trabelsi, Meriam Ben Ayed, Hela Amouri, Rim Duda, John Eric Farrer, Matthew John Hentati, Faycal TI Cognitive dysfunction in Tunisian LRRK2 associated Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; PARK8; LRRK2 gene; G2019S mutation; Neuropsychological study ID PENETRANCE; MUTATIONS; FAMILIES; GENE AB Background: Cognitive impairment and dementia are frequent and debilitating features associated with idiopathic Parkinson's disease (PD). However the prevalence and the pattern of these complications are lacking for LRRK2 (leucine-rich kinase 2)-associated PD patients. Purpose: The purpose of this study was to assess cognitive function in LRRK2- associated PD patients. Material and methods: 55 patients diagnosed with PD-related LRRK2 G2019S mutation were included in the study and compared to the same number of G2019S non-carriers PD patients. Age, sex, disease duration, the movement disorder society-unified Parkinson's Disease rating scale (MDS-UPDRS), Hoehn and Yahr stage, Schwab and England scale and the 30-item geriatric depression scale (GDS) scores were noted. Cognitive assessment included MMSE (Mini-Mental Examination), MOCA (Montreal Cognitive Assessment) and FAB (Frontal Assessment Battery). Results: MMSE, MOCA and FAB performance in G2019S carriers PD patients was similar to that of non-carriers. In both groups, performance was primarily impaired on visuospatial and executive tasks. Cognitive impairment was associated with older age, lower educational level and increased severity of motor impairment. Conclusion: Cognitive functions were similarly affected in PD patients with and without LRRK2 G2019S mutation with mainly impaired visuospatial and executive abilities. However, these results need to be confirmed by further large and prospective studies. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Ben Sassi, Samia; Nabli, Fatma; Hentati, Emna; Nahdi, Houda; Trabelsi, Meriam; Ben Ayed, Hela; Amouri, Rim; Hentati, Faycal] Natl Inst Neurol, Dept Neurol, Tunis 1007, Tunisia. [Duda, John Eric] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. [Farrer, Matthew John] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. RP Ben Sassi, S (reprint author), Natl Inst Neurol, Dept Neurol, Tunis 1007, Tunisia. EM bensassisam@yahoo.fr FU Michael J. Fox Foundation FX This study was supported by a grant from the Michael J. Fox Foundation. NR 12 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD MAR PY 2012 VL 18 IS 3 BP 243 EP 246 DI 10.1016/j.parkreldis.2011.10.009 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 912PX UT WOS:000301813200007 PM 22056842 ER PT J AU Baggish, AL Thompson, PD AF Baggish, Aaron L. Thompson, Paul D. TI Cardiovascular care of the Athletic Patient Introduction SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Editorial Material C1 [Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. [Thompson, Paul D.] Hartford Hosp, Henry Low Heart Ctr, Hartford, CT 06115 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. EM abaggish@partners.org; Pthomps@harthosp.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAR-APR PY 2012 VL 54 IS 5 BP 379 EP 379 DI 10.1016/j.pcad.2012.02.002 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 908SN UT WOS:000301511400001 PM 22386287 ER PT J AU Weiner, RB Baggish, AL AF Weiner, Rory B. Baggish, Aaron L. TI Exercise-Induced Cardiac Remodeling SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID LEFT-VENTRICULAR HYPERTROPHY; PROFESSIONAL SOCCER PLAYERS; FLOW PROPAGATION VELOCITY; INTRINSIC HEART-RATE; ATHLETES HEART; LEFT ATRIAL; DIASTOLIC FUNCTION; ETHNIC-DIFFERENCES; PHYSICAL-FITNESS; TRAINED CYCLISTS AB Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes. (Prog Cardiovasc Dis 2012;54:380-386) (C) 2012 Elsevier Inc. All rights reserved. C1 [Weiner, Rory B.; Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, Boston, MA 02114 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM abaggish@partners.org NR 72 TC 25 Z9 27 U1 3 U2 19 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAR-APR PY 2012 VL 54 IS 5 BP 380 EP 386 DI 10.1016/j.pcad.2012.01.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 908SN UT WOS:000301511400002 PM 22386288 ER PT J AU Humphreys, KL Foley, KM Feinstein, BA Marx, BP Kaloupek, DG Keane, TM AF Humphreys, Kathryn L. Foley, Kristen M. Feinstein, Brian A. Marx, Brian P. Kaloupek, Danny G. Keane, Terence M. TI The Influence of Externalizing Comorbidity on Psychophysiological Reactivity Among Veterans With Posttraumatic Stress Disorder SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress disorder; antisocial personality disorder; substance use disorder; comorbidity; physiological reactivity; Veterans ID COGNITIVE PROCESSING THERAPY; SUBSTANCE USE DISORDERS; DSM-III-R; VIETNAM VETERANS; INTERNALIZING SUBTYPES; ANTISOCIAL-BEHAVIOR; MENTAL-DISORDERS; PERSONALITY; DEPENDENCE; DIAGNOSIS AB Although most individuals with posttraumatic stress disorder (PTSD) demonstrate heightened physiological reactivity to trauma-related cues, many of these individuals do not. The presence of comorbid externalizing disorders is a potential explanation for this inconsistency. This study investigated the psychophysiological reactions to both standardized and idiographic trauma-related cues among male Vietnam Veterans with PTSD only, PTSD and a comorbid substance use disorder (PTSD-SUD), PTSD and comorbid antisocial personality disorder (PTSD-ASPD), PTSD and both comorbid ASPD and SUD (PTSD-ASPD/SUD), and healthy controls. Results showed that the heart rate reactivity of the PTSD-ASPD and PTSD-ASPD/SUD groups failed to exceed that of the No Disorder group during the imagery-based task, and the PTSD-ASPD/SUD group showed less skin conductance reactivity than the other three PTSD groups in response to the standardized trauma cues. These findings implicate ASPD comorbidity in reduced physiological reactivity to trauma reminders in some individuals with PTSD. C1 [Humphreys, Kathryn L.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Foley, Kristen M.; Feinstein, Brian A.; Marx, Brian P.; Kaloupek, Danny G.; Keane, Terence M.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA USA. [Marx, Brian P.; Kaloupek, Danny G.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Marx, BP (reprint author), 150 S Huntington Ave,116B-4, Boston, MA 02130 USA. EM brian.marx@va.gov OI Kaloupek, Danny/0000-0002-0795-593X NR 47 TC 3 Z9 3 U1 2 U2 7 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD MAR PY 2012 VL 4 IS 2 BP 145 EP 151 DI 10.1037/a0022644 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 910GI UT WOS:000301624800001 ER PT J AU Heyworth, MF AF Heyworth, Martin F. TI Changing prevalence of human microsporidiosis SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE Microsporidiosis; Microsporidia; AIDS; HIV ID ENTEROCYTOZOON-BIENEUSI; ENCEPHALITOZOON-INTESTINALIS AB The frequency of publications about microsporidiosis, indexed in PubMed, was tracked on a yearly basis from 1980 to 2010. Search terms (individual and paired) of various degrees of restrictiveness were used (ranging from least restrictive: 'microsporidia', to most restrictive: 'microsporidiosis/HIV', 'microsporidiosis/AIDS'). The annual number of publications indexed under each search term(s) increased from the early 1980s until the mid 1990s. In subsequent years, there was a decline in numbers of publications retrievable via search terms emphasising human disease. This decline mirrors the declining prevalence of microsporidian infections in the HIV-infected population since the mid to late 1990s. Published by Elsevier Ltd on behalf of Royal Society of Tropical Medicine and Hygiene. C1 [Heyworth, Martin F.] Dept Vet Affairs Med Ctr, Res Serv, Philadelphia, PA 19104 USA. [Heyworth, Martin F.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Heyworth, MF (reprint author), Dept Vet Affairs Med Ctr, Res Serv, Philadelphia, PA 19104 USA. EM martin.heyworth@va.gov NR 10 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD MAR PY 2012 VL 106 IS 3 BP 202 EP 204 DI 10.1016/j.trstmh.2011.11.005 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 910HD UT WOS:000301626900012 PM 22261187 ER PT J AU Bodnar, RJ Rodgers, ME Wells, A AF Bodnar, R. J. Rodgers, M. E. Wells, A. TI PERICYTE REGULATION OF VASCULAR REMODELING THROUGH THE CXC RECEPTOR 3 SO WOUND REPAIR AND REGENERATION LA English DT Meeting Abstract C1 [Bodnar, R. J.; Rodgers, M. E.; Wells, A.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Bodnar, R. J.; Wells, A.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2012 VL 20 IS 2 BP A16 EP A16 PG 1 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 901DY UT WOS:000300943100017 ER PT J AU Garfield, CF Dorsey, ER Zhu, S Huskamp, HA Conti, R Dusetzina, SB Higashi, A Perrin, JM Kornfield, R Alexander, GC AF Garfield, Craig F. Dorsey, E. Ray Zhu, Shu Huskamp, Haden A. Conti, Rena Dusetzina, Stacie B. Higashi, Ashley Perrin, James M. Kornfield, Rachel Alexander, G. Caleb TI Trends in Attention Deficit Hyperactivity Disorder Ambulatory Diagnosis and Medical Treatment in the United States, 2000-2010 SO ACADEMIC PEDIATRICS LA English DT Article DE attention deficit and hyperactivity disorder; pediatrics; pediatric workforce; mental health ID CLINICAL-PRACTICE GUIDELINE; DEFICIT/HYPERACTIVITY DISORDER; CHILDREN; ADOLESCENTS; ADHD; ATOMOXETINE; SUICIDALITY; PREVALENCE; ADULTS; IMPACT AB OBJECTIVES: Because of several recent clinical and regulatory changes regarding attention deficit-hyperactivity disorder (ADHD) in the United States, we quantified changes in the diagnosis of ADHD and its pharmacologic treatment from 2000 through 2010. METHODS: We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of office-based providers, to examine aggregate trends among children and adolescents younger than 18 yeasrs of age. We also quantified how diagnosis and treatment patterns have evolved on the basis of patient and physician characteristics and the therapeutic classes used. RESULTS: From 2000 to 2010, the number of physician outpatient visits in which ADHD was diagnosed increased 66% from 6.2 million (95% confidence interval 5.5-6.9M) to 10.4 million visits (95% confidence interval 9.3-11.6 million). Of these visits, psychostimulants have remained the dominant treatment; they were used in 96% of treatment visits in 2000 and 87% of treatment visits in 2010. Atomoxetine use decreased from 15% of treatment visits upon product launch in 2003 to 6% of treatment visits by 2010. The use of potential substitute therapies clonidine, guanfacine, and bupropion-remained relatively constant (between 5% and 9% of treatment visits) during most of the period examined. During this period, the management of ADHD shifted away from pediatricians and towards psychiatrists (from 24% to 36% of all visits) without large changes in illness severity or the proportion of ADHD treatment visits accounted for by males (73%-77%). CONCLUSIONS: In 10 years, the ambulatory diagnosis of ADHD increased by two-thirds and is increasingly managed by psychiatrists. The effects of these changing treatment patterns on children's health outcomes and their families are unknown. C1 [Conti, Rena; Alexander, G. Caleb] Univ Chicago, Ctr Hlth & Social Sci, Chicago, IL 60637 USA. [Garfield, Craig F.] Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA. [Garfield, Craig F.] Northwestern Univ, Dept Med Social Sci, Chicago, IL 60611 USA. [Dorsey, E. Ray] Dept Neurol, Baltimore, MD USA. [Zhu, Shu; Higashi, Ashley; Kornfield, Rachel; Alexander, G. Caleb] Univ Chicago Hosp, Dept Med, Chicago, IL 60637 USA. [Huskamp, Haden A.; Dusetzina, Stacie B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Conti, Rena] Univ Chicago Hosp, Dept Pediat, Chicago, IL 60637 USA. [Perrin, James M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Alexander, G. Caleb] Univ Illinois, Sch Pharm, Dept Pharm Practice, Chicago, IL USA. RP Alexander, GC (reprint author), Univ Chicago, Ctr Hlth & Social Sci, 5841 S Maryland,MC 2007, Chicago, IL 60637 USA. EM galexand@uchicago.edu FU Agency for Healthcare Research and Quality [RO1 HS0189960]; Robert Wood Johnson Physician Faculty; Robert Wood Johnson Foundation; Ruth L. Kirschstein-National Service [T32 MH019733-17] FX Funding This work was supported by the Agency for Healthcare Research and Quality (RO1 HS0189960). Dr. Dorsey was supported by the Robert Wood Johnson Physician Faculty Scholars Program and Dr. Huskamp was supported by a Robert Wood Johnson Foundation Investigator Award in Health Policy Research. Dr. Dusetzina was supported by a Ruth L. Kirschstein-National Service Research Award (T32 MH019733-17). The funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or approval of the manuscript for publication. NR 25 TC 35 Z9 35 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD MAR-APR PY 2012 VL 12 IS 2 BP 110 EP 116 PG 7 WC Pediatrics SC Pediatrics GA 910HE UT WOS:000301627000007 PM 22326727 ER PT J AU Sonnenberg, A AF Sonnenberg, Amnon TI Management of Delayed Postpolypectomy Bleeding: A Decision Analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID COLONOSCOPIC POLYPECTOMY; RISK-FACTORS; HEMORRHAGE AB OBJECTIVES: The benefit of repeat colonoscopy in managing delayed postpolypectomy bleeding is unknown. This study aimed to assess the outcome of repeat colonoscopy to achieve hemostasis. METHODS: Endoscopic management of postpolypectomy bleeding is modeled as a decision tree, measuring the expected overall fraction of patients who benefit from therapeutic hemostasis and the number of patients needed to treat (NNT) in order to achieve one beneficial hemostasis. RESULTS: A repeat colonoscopy to identify and treat postpolypectomy bleeding is beneficial in about 22% of patients, corresponding to an NNT of 4.5 patients. The outcome of the model is sensitive to assumptions underlying the fractions of patients who need treatment and would benefit from successful endoscopic hemostasis. Varying these probabilities over a broad range changes the fraction of patients benefiting from endoscopy between 3% and 33% and the NNT between 28 and 3 patients, respectively. CONCLUSIONS: The expected outcome of repeat colonoscopy justifies the endoscopic attempts at therapeutic hemostasis. The results also suggest that in many patients expectant management aimed at spontaneous resolution of the bleeding remains a valid option. C1 [Sonnenberg, Amnon] Portland VA Med Ctr, Portland, OR 97239 USA. [Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 18 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAR PY 2012 VL 107 IS 3 BP 339 EP 342 DI 10.1038/ajg.2011.426 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 908NH UT WOS:000301496600002 PM 22388016 ER PT J AU Laine, L Jensen, DM AF Laine, Loren Jensen, Dennis M. TI Management of Patients With Ulcer Bleeding SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID UPPER-GASTROINTESTINAL HEMORRHAGE; RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE ASPIRIN; HELICOBACTER-PYLORI INFECTION; PROTON PUMP INHIBITORS; DOUBLE-BLIND TRIAL; ENDOSCOPIC INJECTION THERAPY; NONBLEEDING VISIBLE VESSELS; CORONARY-ARTERY-DISEASE; UPPER-GI HEMORRHAGE AB This guideline presents recommendations for the step-wise management of patients with overt upper gastrointestinal bleeding. Hemodynamic status is first assessed, and resuscitation initiated as needed. Patients are risk-stratified based on features such as hemodynamic status, comorbidities, age, and laboratory tests. Pre-endoscopic erythromycin is considered to increase diagnostic yield at first endoscopy. Pre-endoscopic proton pump inhibitor (PPI) may be considered to decrease the need for endoscopic therapy but does not improve clinical outcomes. Upper endoscopy is generally performed within 24 h. The endoscopic features of ulcers direct further management. Patients with active bleeding or non-bleeding visible vessels receive endoscopic therapy (e.g., bipolar electrocoagulation, heater probe, sclerosant, clips) and those with an adherent clot may receive endoscopic therapy; these patients then receive intravenous PPI with a bolus followed by continuous infusion. Patients with flat spots or clean-based ulcers do not require endoscopic therapy or intensive PPI therapy. Recurrent bleeding after endoscopic therapy is treated with a second endoscopic treatment; if bleeding persists or recurs, treatment with surgery or interventional radiology is undertaken. Prevention of recurrent bleeding is based on the etiology of the bleeding ulcer. H. pylori is eradicated and after cure is documented anti-ulcer therapy is generally not given. Nonsteroidal anti-inflammatory drugs (NSAIDs) are stopped; if they must be resumed low-dose COX-2-selective NSAID plus PPI is used. Patients with established cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding ceases (within 7 days and ideally 1-3 days). Patients with idiopathic ulcers receive long-term anti-ulcer therapy. C1 [Laine, Loren] Yale Univ, Sch Med, Sect Digest Dis, New Haven, CT 06520 USA. [Laine, Loren] VA Connecticut Healthcare Syst, New Haven, CT USA. [Jensen, Dennis M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Jensen, Dennis M.] CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Jensen, Dennis M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Laine, L (reprint author), Yale Univ, Sch Med, Sect Digest Dis, 333 Cedar St,1080 LMP, New Haven, CT 06520 USA. EM loren.laine@yale.edu FU Boston Scientific; Pentax; Olympus; US Endoscopy; Vascular Technology Inc. FX L. Laine has served as a consultant for AstraZeneca, Eisai, Pfizer, Horizon, and Logical Therapeutics, and has served on Data Safety Monitoring Boards for Bayer, BMS, and Merck. D. Jensen is a consultant for AstraZeneca, Boston Scientific, Merck, and US Endoscopy. D. Jensen has received research grants from Boston Scientific, Pentax, Olympus, US Endoscopy, and Vascular Technology Inc. NR 133 TC 139 Z9 157 U1 5 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAR PY 2012 VL 107 IS 3 BP 345 EP 361 DI 10.1038/ajg.2011.480 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 908NH UT WOS:000301496600003 PM 22310222 ER PT J AU Shahian, DM Iezzoni, LI Meyer, GS Kirle, L Normand, SLT AF Shahian, David M. Iezzoni, Lisa I. Meyer, Gregg S. Kirle, Leslie Normand, Sharon-Lise T. TI Hospital-wide Mortality as a Quality Metric: Conceptual and Methodological Challenges SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article DE hospital-wide mortality; performance metrics ID RISK-ADJUSTED MORTALITY; ACUTE MYOCARDIAL-INFARCTION; ADULT CARDIAC-SURGERY; BYPASS GRAFT-SURGERY; ADMINISTRATIVE DATABASES; CORONARY INTERVENTION; OF-CARE; SURGICAL MORTALITY; MEDICAL DIAGNOSES; CLINICAL-OUTCOMES AB Hospital-wide mortality rates are used as a measure of overall hospital quality. However, their parsimony and apparent simplicity belie significant conceptual and methodological concerns. For many diagnoses included in hospital-wide mortality, the association between short-term mortality and quality of care is not well established. Furthermore, compared with condition-specific or procedure-specific mortality, hospital-wide mortality rates pose greater methodological challenges (ie, eligibility and exclusion criteria, risk adjustment, statistical techniques for aggregating across diagnoses, usability). Many of these result from substantial interprovider heterogeneity in diagnosis frequency, sample sizes, and patient severity. Hospital-wide mortality is problematic as a quality metric for public reporting, although hospitals may elect to use such measures for other purposes. Potential alternative approaches include multidimensional composite metrics or mortality measurement limited to selected conditions and procedures for which the link between hospital mortality and quality is clear, legitimate exclusions are uncommon, and sample sizes, end points, and risk adjustment are adequate. C1 [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Shahian, David M.; Iezzoni, Lisa I.; Meyer, Gregg S.; Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Boston, MA USA. [Kirle, Leslie] Kirle Consulting, Boston, MA USA. RP Shahian, DM (reprint author), Massachusetts Gen Hosp, Ctr Qual & Safety, 55 Fruit St, Boston, MA 02114 USA. EM dshahian@partners.org FU Division of Health Care Finance & Policy, Executive Office of Health and Human Services, Commonwealth of Massachusetts, Boston, MA. FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The efforts of Drs Shahian, Iezzoni, and Normand and Ms Kirle were funded by a contract with the Division of Health Care Finance & Policy, Executive Office of Health and Human Services, Commonwealth of Massachusetts, Boston, MA. NR 98 TC 10 Z9 11 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1062-8606 EI 1555-824X J9 AM J MED QUAL JI Am. J. Med. Qual. PD MAR-APR PY 2012 VL 27 IS 2 BP 112 EP 123 DI 10.1177/1062860611412358 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 907ZY UT WOS:000301461000005 PM 21918014 ER PT J AU Umezawa, K Branch, J Hasegawa, K AF Umezawa, Kougaku Branch, Joel Hasegawa, Kohei TI IMAGES IN EMERGENCY MEDICINE Pott's puffy tumor with subdural empyema SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material C1 [Umezawa, Kougaku] Shonan Kamakura Gen Hosp, Dept Emergency Med, Kamakura, Kanagawa, Japan. [Branch, Joel] Shonan Kamakura Gen Hosp, Dept Gen Internal Med, Kamakura, Kanagawa, Japan. [Hasegawa, Kohei] Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Umezawa, K (reprint author), Shonan Kamakura Gen Hosp, Dept Emergency Med, Kamakura, Kanagawa, Japan. NR 2 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2012 VL 59 IS 3 BP 234 EP + DI 10.1016/j.annemergmed.2011.06.016 PG 2 WC Emergency Medicine SC Emergency Medicine GA 905MM UT WOS:000301276300020 PM 22340802 ER PT J AU Profit, J Etchegaray, J Petersen, LA Sexton, JB Hysong, SJ Mei, MH Thomas, EJ AF Profit, Jochen Etchegaray, Jason Petersen, Laura A. Sexton, J. Bryan Hysong, Sylvia J. Mei, Minghua Thomas, Eric J. TI The Safety Attitudes Questionnaire as a tool for benchmarking safety culture in the NICU SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION LA English DT Article ID NEONATAL INTENSIVE-CARE; COLLABORATIVE QUALITY IMPROVEMENT; PATIENT SAFETY; RANDOMIZED-TRIAL; OF-CARE; CLIMATE; UNITS; TEAMWORK AB Background Neonatal intensive care unit (NICU) safety culture, as measured by the Safety Attitudes Questionnaire (SAQ), varies widely. Associations with clinical outcomes in the adult intensive care unit setting make the SAQ an attractive tool for comparing clinical performance between hospitals. Little information is available on the use of the SAQ for this purpose in the NICU setting. Objectives To determine whether the dimensions of safety culture measured by the SAQ give consistent results when used as a NICU performance measure. Methods Cross-sectional survey of caregivers in 12 NICUs, using the six scales of the SAO: teamwork climate, safety climate, job satisfaction, stress recognition, perceptions of management and working conditions. NICUs were ranked by quantifying their contribution to overall risk-adjusted variation across the scales. Spearman rank correlation coefficients were used to test for consistency in scale performance. The authors then examined whether performance in the top four NICUs in one scale predicted top four performance in others. Results There were 547 respondents in 12 NICUs. Of 15 NICU-level correlations in performance ranking, two were >0.7, seven were between 0.4 and 0.69, and the six remaining were <0.4. The authors found a trend towards significance in comparing the distribution of performance in the top four NICUs across domains with a binomial distribution p=0.051, indicating generally consistent performance across dimensions of safety culture. Conclusion A culture of safety permeates many aspects of patient care and organisational functioning. The SAQ may be a useful tool for comparative performance assessments among NICUs. C1 [Profit, Jochen] Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Texas Childrens Hosp, Dept Pediat,Sect Neonatol, Houston, TX 77030 USA. [Profit, Jochen; Petersen, Laura A.; Mei, Minghua] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. [Profit, Jochen; Petersen, Laura A.; Hysong, Sylvia J.; Mei, Minghua] VA Med Ctr, Houston Vet Affairs VA Hlth Serv Res & Dev, Ctr Excellence, Hlth Policy & Qual Program,Michael DeBakey VA Med, Houston, TX USA. [Etchegaray, Jason; Thomas, Eric J.] Univ Texas Houston, Sch Med, Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. [Sexton, J. Bryan] Duke Univ, Dept Psychiat, Sch Med, Duke Univ Hlth Syst, Durham, NC 27706 USA. RP Profit, J (reprint author), Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Texas Childrens Hosp, Dept Pediat,Sect Neonatol, VA HSR&D 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM profit@bcm.edu RI Hysong, Sylvia/B-8420-2008; OI Hysong, Sylvia/0000-0002-9063-5207; Etchegaray, Jason/0000-0002-3427-796X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [1 K23 HD056298-01, 1 K24 HD053771-01, 1 PO1 HS1154401]; American Heart Association [0540043N]; Veterans Administration Center (VA HSRD CoE) [HFP90-20]; Department of Veterans Affairs Health Services [CD 2-07-0818]; Agency for Healthcare Research and Quality (AHRQ) [1UC1HS014246, 1 K02 HS017145-02]; University of Texas at Houston - Memorial Hermann Center for Quality and Safety FX JP's contribution is supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (#1 K23 HD056298-01, PI: Profit). LAP was a recipient of the American Heart Association Established Investigator Award (#0540043N) at the time that this work was carried out. LAP, SJH and MM also receive support from a Veterans Administration Center Grant (VA HSR&D CoE HFP90-20). SJH's contribution is supported in part by the Department of Veterans Affairs Health Services Research and Development Program (#CD 2-07-0818). EJT's effort is supported in part by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (#1 K24 HD053771-01, PI: Thomas and #1 PO1 HS1154401, PI: Thomas). JBS received support from the Agency for Healthcare Research and Quality (AHRQ) (grant # 1UC1HS014246). JE's effort is supported by a K02 award from AHRQ (#1 K02 HS017145-02) and the University of Texas at Houston - Memorial Hermann Center for Quality and Safety. NR 31 TC 14 Z9 16 U1 2 U2 13 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1359-2998 J9 ARCH DIS CHILD-FETAL JI Arch. Dis. Child.-Fetal Neonatal Ed. PD MAR PY 2012 VL 97 IS 2 BP F127 EP F132 DI 10.1136/archdischild-2011-300612 PG 6 WC Pediatrics SC Pediatrics GA 910JU UT WOS:000301633800010 PM 22337935 ER PT J AU Gao, X Simon, KC Schwarzschild, MA Ascherio, A AF Gao, Xiang Simon, Kelly C. Schwarzschild, Michael A. Ascherio, Alberto TI Prospective Study of Statin Use and Risk of Parkinson Disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID LIPOPROTEIN CHOLESTEROL LEVELS; COA REDUCTASE INHIBITORS; LIPID-LOWERING DRUGS; COENZYME Q(10); URATE; MEN; ATORVASTATIN; SIMVASTATIN; EXPRESSION; LOVASTATIN AB Objective: To prospectively examine whether use of statins is associated with altered risk of Parkinson disease (PD). Design, Setting, and Participants: A prospective study including 38 192 men and 90 874 women participating in 2 ongoing US cohorts, the Health Professional Follow-up Study and the Nurses' Health Study, was conducted. Information on regular cholesterol-lowering drug use (>= 2 times/wk) was collected in 1994 in both cohorts via questionnaire. Relative risks (RRs) and 95% CIs were computed using Cox proportional hazards models adjusting for age, smoking, caffeine intake, duration of hypercholesterolemia, and other covariates. Main Outcome Measure: Incident PD. Results: During 12 years of follow-up (1994-2006), we documented 644 incident PD cases (338 women and 306 men). The risk of PD was lower among current statin users (adjusted pooled RR=0.74; 95% CI, 0.54-1.00; P=.049) relative to nonusers. A significant association was observed in participants younger than 60 years at baseline (adjusted pooled RR=0.31; 95% CI, 0.11-0.86; P=.02) but not among those who were older (adjusted pooled RR=0.83; 95% CI, 0.60-1.14; P=.25) (P for interaction=.03). Conclusions: We found that regular use of statins was associated with a modest reduction in PD risk. The possibility that some statins may reduce PD risk deserves further consideration. C1 [Gao, Xiang; Simon, Kelly C.; Ascherio, Alberto] Harvard Univ, Dept Med, Channing Lab, Brigham & Womens Hosp,Sch Publ Hlth,Dept Nutr, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Dept Med, Channing Lab, Brigham & Womens Hosp,Sch Publ Hlth,Dept Epidemio, Boston, MA 02115 USA. [Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gao, X (reprint author), Harvard Univ, Dept Med, Channing Lab, Brigham & Womens Hosp,Sch Publ Hlth,Dept Nutr, 181 Longwood Ave, Boston, MA 02115 USA. EM xiang.gao@channing.harvard.edu FU National Institute of Neurological Disorders and Stroke, National Institutes of Health [R01 NS048517, R01 NS061858, P01 CA055075, P01 CA87969, K24NS060991] FX This study was supported by grants R01 NS048517, R01 NS061858, P01 CA055075, P01 CA87969, and K24NS060991 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 34 TC 43 Z9 49 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2012 VL 69 IS 3 BP 380 EP 384 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 906VQ UT WOS:000301377300013 PM 22410446 ER PT J AU Ladapo, JA Kymes, SM Ladapo, JA Nwosu, VC Pasquale, LR AF Ladapo, Joseph A. Kymes, Steven M. Ladapo, Jonathan A. Nwosu, Veronica C. Pasquale, Louis R. TI Projected Clinical Outcomes of Glaucoma Screening in African American Individuals SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; QUALITY-OF-LIFE; NORMAL-TENSION GLAUCOMA; VISUAL-FIELD LOSS; UNITED-STATES; INTRAOCULAR-PRESSURE; OCULAR HYPERTENSION; COST-EFFECTIVENESS; PREVALENCE; METAANALYSIS AB Objectives: To project the clinical impact of routine glaucoma screening on visual outcomes in middle-aged African American individuals and help guide glaucoma screening policy. Methods: Using data from the Eye Diseases Prevalence Research Group and Baltimore Eye Study, we developed a microsimulation model to project visual outcomes in African American individuals screened for glaucoma under a national screening policy using frequency-doubling technology. We projected the impact of universal screening on glaucoma-related visual impairment (acuity worse than 20/40 but better than 20/200 in the better-seeing eye) and blindness (acuity 20/200 or worse in the better-seeing eye). The diagnostic characteristics of frequency-doubling technology and the hazard ratio for glaucoma progression in treated patients were informed by meta-analyses of randomized controlled trials. Results: Implementation of a national glaucoma screening policy for a cohort of African American individuals between the ages of 50 and 59 years without known glaucoma would reduce the lifetime prevalence of undiagnosed glaucoma from 50% to 27%, the prevalence of glaucoma- related visual impairment from 4.6% to 4.4% (4.1% relative decrease), and the prevalence of glaucoma-related blindness from 6.1% to 5.6% (7.1% relative decrease). We project the cost of the program to be $80 per screened individual, considering only the cost of frequency-doubling technology and confirmatory eye examinations. The number needed to screen to diagnose 1 person with glaucoma is 58. The number needed to screen to prevent 1 person from developing visual impairment is 875. Conclusions: Routine glaucoma screening for middle-aged African American individuals is potentially clinically effective but its impact on visual impairment and blindness may be modest. However, we did not assess the impact on visual field loss. C1 [Ladapo, Joseph A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ladapo, Joseph A.; Pasquale, Louis R.] Harvard Univ, Sch Med, Boston, MA USA. [Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Pasquale, Louis R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Kymes, Steven M.] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. [Kymes, Steven M.] Washington Univ, Sch Med, Ctr Econ Evaluat Med, St Louis, MO 63110 USA. [Ladapo, Jonathan A.; Nwosu, Veronica C.] N Carolina Cent Univ, Dept Biol, Durham, NC USA. RP Ladapo, JA (reprint author), NYU, Sch Med, Dept Med, 550 1st Ave,Room 614, New York, NY 10075 USA. EM joseph.ladapo@nyumc.org; joseph.ladapo@nyumc.org OI Ladapo, Joseph/0000-0002-8518-4800 FU Research to Prevent Blindness; National Institutes of Health [R01 EY015473] FX Funding for this research was provided through a Physician Scientist Award from Research to Prevent Blindness (Dr Pasquale) and National Institutes of Health grant R01 EY015473 (Dr Pasquale). NR 49 TC 7 Z9 7 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2012 VL 130 IS 3 BP 365 EP 372 PG 8 WC Ophthalmology SC Ophthalmology GA 906NW UT WOS:000301353400015 PM 22411665 ER PT J AU Jean, D Daubriac, J Le Pimpec-Barthes, F Galateau-Salle, F Jaurand, MC AF Jean, Didier Daubriac, Julien Le Pimpec-Barthes, Francoise Galateau-Salle, Francoise Jaurand, Marie-Claude TI Molecular Changes in Mesothelioma With an Impact on Prognosis and Treatment SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID MALIGNANT PLEURAL MESOTHELIOMA; ENDOTHELIAL GROWTH-FACTOR; COMPARATIVE GENOMIC HYBRIDIZATION; ABERRANT PROMOTER METHYLATION; UBIQUITIN-PROTEASOME PATHWAY; RECEPTOR TYROSINE KINASES; APOPTOSIS-INDUCING LIGAND; IN-SITU HYBRIDIZATION; CELL-CYCLE CONTROL; DNA METHYLATION AB Context.-In recent decades, research on malignant pleural mesothelioma (MPM) has been developed to improve patients' outcomes by increasing the level of confidence in MPM diagnosis and prognosis. Objective.-To summarize data on genetic and epigenetic abnormalities in MPM that may be of interest for a better management of patients with MPM. Data Sources.-Data were obtained from scientific publications on genetic and epigenetic abnormalities in MPM by studying gene mutations, DNA methylation, and gene and microRNA expression profiling. Conclusions.-Molecular changes in MPM consist in altered expression and in activation or inactivation of critical genes in oncogenesis, especially tumor suppressor genes at the INK4 and NF2 loci. Activation of membrane receptor tyrosine kinases and deregulation of signaling pathways related to differentiation, survival, proliferation, apoptosis, cell cycle control, metabolism, migration, and invasion have been demonstrated. Alterations that could be targeted at a global level (methylation) have been recently reported. Experimental research has succeeded especially in abolishing proliferation and triggering apoptosis in MPM cells. So far, targeted clinical approaches focusing on receptor tyrosine kinases have had limited success. Molecular analyses of series of MPM cases have shown that defined alterations are present in MPM subsets, consistent with interindividual variations of molecular alterations, and suggesting that identification of patient subgroupswill be essential to develop more specific therapies. (Arch Pathol Lab Med. 2012;136:277-293; doi:10.5858/arpa.2011-0215-RA) C1 [Jean, Didier; Le Pimpec-Barthes, Francoise; Jaurand, Marie-Claude] Univ Paris 05, INSERM, UMR S674, U674, F-75010 Paris, France. [Daubriac, Julien] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA USA. [Le Pimpec-Barthes, Francoise] Hop Europeen Georges Pompidou, AP HP, Serv Chirurg Thorac, Paris, France. [Galateau-Salle, Francoise] Hop Cote de Nacre, Serv Anat Pathol, Caen, France. [Galateau-Salle, Francoise] INSERM, ERI3, Caen, France. RP Jaurand, MC (reprint author), Univ Paris 05, INSERM, UMR S674, U674, 27 Rue Juliette Dodu, F-75010 Paris, France. EM marie-claude.jaurand@inserm.fr RI JEAN, Didier/A-1615-2009; Galateau Salle, Francoise/J-1530-2015 OI JEAN, Didier/0000-0001-5823-7404; Galateau Salle, Francoise/0000-0003-3642-0165 NR 192 TC 32 Z9 33 U1 0 U2 12 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2012 VL 136 IS 3 BP 277 EP 293 DI 10.5858/arpa.2011-0215-RA PG 17 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 907JS UT WOS:000301414200012 PM 22372904 ER PT J AU Gray, PJ Shipley, WU AF Gray, Phillip J. Shipley, William U. TI The importance of combined radiation and endocrine therapy in locally advanced prostate cancer SO ASIAN JOURNAL OF ANDROLOGY LA English DT Editorial Material ID PHASE-III TRIAL; INTENSITY-MODULATED RADIOTHERAPY; ANDROGEN DEPRIVATION THERAPY; NEOADJUVANT; SUPPRESSION; MANAGEMENT; CARCINOMA; TOXICITY; STAGE; UK C1 [Gray, Phillip J.; Shipley, William U.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Gray, Phillip J.] Harvard Radiat Oncol Program, Boston, MA 02114 USA. RP Shipley, WU (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM WShipley@partners.org NR 18 TC 2 Z9 2 U1 0 U2 0 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA SN 1008-682X J9 ASIAN J ANDROL JI Asian J. Androl. PD MAR PY 2012 VL 14 IS 2 BP 245 EP 246 DI 10.1038/aja.2011.177 PG 2 WC Andrology; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 904IZ UT WOS:000301189600013 PM 22198629 ER PT J AU Chittenden, TW Howe, EA Taylor, JM Mar, JC Aryee, MJ Gomez, H Sultana, R Braisted, J Nair, SJ Quackenbush, J Holmes, C AF Chittenden, Thomas W. Howe, Eleanor A. Taylor, Jennifer M. Mar, Jessica C. Aryee, Martin J. Gomez, Harold Sultana, Razvan Braisted, John Nair, Sarita J. Quackenbush, John Holmes, Chris TI nEASE: a method for gene ontology subclassification of high-throughput gene expression data SO BIOINFORMATICS LA English DT Article ID ENRICHMENT ANALYSIS; SET ENRICHMENT; TOOLS; OVERREPRESENTATION; SOFTWARE; DESIGN; LISTS AB High-throughput technologies can identify genes whose expression profiles correlate with specific phenotypes; however, placing these genes into a biological context remains challenging. To help address this issue, we developed nested Expression Analysis Systematic Explorer (nEASE). nEASE complements traditional gene ontology enrichment approaches by determining statistically enriched gene ontology subterms within a list of genes based on co-annotation. Here, we overview an open-source software version of the nEASE algorithm. nEASE can be used either stand-alone or as part of a pathway discovery pipeline. Availability: nEASE is implemented within the Multiple Experiment Viewer software package available at http://www.tm4.org/mev. C1 [Chittenden, Thomas W.; Howe, Eleanor A.; Holmes, Chris] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Chittenden, Thomas W.; Howe, Eleanor A.; Mar, Jessica C.; Gomez, Harold; Sultana, Razvan; Nair, Sarita J.; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Chittenden, Thomas W.; Mar, Jessica C.; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Chittenden, Thomas W.; Mar, Jessica C.; Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Taylor, Jennifer M.] CSIRO Plant Ind, Bioinformat Grp, Canberra, ACT, Australia. [Aryee, Martin J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Aryee, Martin J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Braisted, John] J Craig Venter Inst, Rockville, MD USA. [Holmes, Chris] MRC Mammalian Genet Unit, Harwell, Berks, England. RP Holmes, C (reprint author), Univ Oxford, Dept Stat, Oxford OX1 3TG, England. EM cholmes@stats.ox.ac.uk RI Taylor, Jennifer/A-1686-2010 OI Taylor, Jennifer/0000-0003-4231-0181 FU Medical Research Council, UK FX C.H. is supported by the Medical Research Council, UK. NR 18 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAR 1 PY 2012 VL 28 IS 5 BP 726 EP 728 DI 10.1093/bioinformatics/bts011 PG 3 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 901SH UT WOS:000300986600022 PM 22247278 ER PT J AU Tohen, M Bowden, C Berk, M Berlanga, C Andrade, C Broich, K Calabrese, JR Frank, E Geddes, J Goodwin, G Ha, K Hirschfeld, B Kanba, S Keck, P Lafer, B Licht, R Nierenberg, A Nolen, WA Suppes, T Tamayo, J Vieta, E Yatham, LN Carlson, B AF Tohen, M. Bowden, C. Berk, M. Berlanga, C. Andrade, C. Broich, K. Calabrese, J. R. Frank, E. Geddes, J. Goodwin, G. Ha, K. Hirschfeld, B. Kanba, S. Keck, P. Lafer, B. Licht, R. Nierenberg, A. Nolen, W. A. Suppes, T. Tamayo, J. Vieta, E. Yatham, L. N. Carlson, B. TI Design of clinical trials in bipolar disorders SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 5th Biennial Conference of the International-Society-for-Bipolar-Disorders CY MAR 14-17, 2012 CL Istanbul, TURKEY SP Int Soc Bipolar Disorders DE clinical trial design; bipolar disorder C1 [Tohen, M.; Bowden, C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Berk, M.] Barwon Hlth Swanson Ctr, Geelong, Vic, Australia. [Berlanga, C.] Inst Nacl Psiquiatria, Mexico City, DF, Mexico. [Andrade, C.] Natl Inst Mental Hlth & Neurosci, Bangalore 560029, Karnataka, India. [Broich, K.] Fed Inst Drugs & Med Devices, Bonn, Germany. [Calabrese, J. R.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Frank, E.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Geddes, J.; Goodwin, G.] Univ Oxford, Oxford, England. [Ha, K.] Seoul Natl Univ, Bundang Hosp, Seoul, South Korea. [Hirschfeld, B.] Univ Texas Med Branch, Galveston, TX USA. [Kanba, S.] Kyushu Univ, Fukuoka 812, Japan. [Keck, P.] Lindner Ctr HOPE, Cincinnati, OH USA. [Lafer, B.] Univ Sao Paulo, Sao Paulo, Brazil. [Licht, R.] Aarhus Univ, Hosp Psychiat, Risskov, Denmark. [Nierenberg, A.] Massachusettes Gen Hosp, Boston, MA USA. [Nolen, W. A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Suppes, T.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Tamayo, J.] CES Univ, Medellin, Colombia. [Vieta, E.] Univ Barcelona, Barcelona, Spain. [Yatham, L. N.] Univ British Columbia Hosp, Vancouver, BC, Canada. [Carlson, B.] Bristol Myers Squibb Co, New York, NY 10154 USA. RI Vieta, Eduard/I-6330-2013; Nolen, Willem/E-9006-2014; Lafer, Beny/F-9390-2015 OI Vieta, Eduard/0000-0002-0548-0053; Lafer, Beny/0000-0002-6132-9999 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2012 VL 14 SU 1 SI SI BP 14 EP 15 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 908ZG UT WOS:000301531000008 ER PT J AU Dias, RS Lafer, B Nierenberg, AA Sachs, GS Joffe, H AF Dias, R. S. Lafer, B. Nierenberg, A. A. Sachs, G. S. Joffe, H. TI Association between Premenstrual Mood Exacerbation in bipolar disorder with reproductive hormone-related mood disturbances: findings from STEP-BD SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 5th Biennial Conference of the International-Society-for-Bipolar-Disorders CY MAR 14-17, 2012 CL Istanbul, TURKEY SP Int Soc Bipolar Disorders DE bipolar; women; postpartum; pregnancy; premenstrual exacerbation; birth control pills C1 [Dias, R. S.; Lafer, B.] Univ Sao Paulo, Sch Med, Bipolar Disorder Res Program, Dept & Inst Psychiat, BR-05508 Sao Paulo, Brazil. [Dias, R. S.; Nierenberg, A. A.; Sachs, G. S.] Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. [Dias, R. S.; Nierenberg, A. A.; Sachs, G. S.] Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. [Joffe, H.] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. RI Lafer, Beny/F-9390-2015; Dias, Rodrigo/N-8985-2013 OI Lafer, Beny/0000-0002-6132-9999; Dias, Rodrigo/0000-0002-1315-7205 NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2012 VL 14 SU 1 SI SI BP 44 EP 44 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 908ZG UT WOS:000301531000080 ER PT J AU Nohesara, S Ghadirivasfi, M Mostafavi, S Ahmadkhaniha, H Eskandari, M Thiagalingam, S Abdolmaleky, HM AF Nohesara, S. Ghadirivasfi, M. Mostafavi, S. Ahmadkhaniha, H. Eskandari, M. Thiagalingam, S. Abdolmaleky, H. M. TI DNA hypomethylation of MB-COMT promoter and the first exon of HTR2A in DNA derived from saliva in schizophrenia and bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 5th Biennial Conference of the International-Society-for-Bipolar-Disorders CY MAR 14-17, 2012 CL Istanbul, TURKEY SP Int Soc Bipolar Disorders DE DNA methylation; epigenetic; MB-COMT; HTR2A; saliva C1 [Nohesara, S.; Ghadirivasfi, M.; Ahmadkhaniha, H.; Abdolmaleky, H. M.] Univ Tehran Med Sci, Mental Hlth Res Ctr, Dept Psychiat, Tehran, Iran. [Mostafavi, S.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Eskandari, M.] Harvard Univ, Sch Med, Lab Nutr & Metab, BIDMC, Boston, MA USA. [Thiagalingam, S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD MAR PY 2012 VL 14 SU 1 SI SI BP 44 EP 44 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 908ZG UT WOS:000301531000079 ER PT J AU Perez-Stable, EJ Viswanath, K Fagan, P Vallone, D Buchting, FO AF Perez-Stable, Eliseo J. Viswanath, K. Fagan, Pebbles Vallone, Donna Buchting, Francisco O. TI Global tobacco inequalities: a new frontier SO CANCER CAUSES & CONTROL LA English DT Editorial Material ID UNITED-STATES; SECONDHAND SMOKE; GENDER; EXPOSURE; RATES; WOMEN; ASIA C1 [Perez-Stable, Eliseo J.] Univ Calif San Francisco, Div Gen Internal Med, Med Effectiveness Res Ctr Diverse Populat, Dept Med,Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Viswanath, K.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Viswanath, K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fagan, Pebbles] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Vallone, Donna] Amer Legacy Fdn, Washington, DC USA. [Buchting, Francisco O.] ETR Associates, Scotts Valley, CA USA. RP Perez-Stable, EJ (reprint author), Univ Calif San Francisco, Div Gen Internal Med, Med Effectiveness Res Ctr Diverse Populat, Dept Med,Helen Diller Family Comprehens Canc Ctr, 3333 Calif St, San Francisco, CA 94143 USA. EM eliseops@medicine.ucsf.edu; Vish_Viswanath@dfci.harvard.edu; pfagan@cc.hawaii.edu; DVallone@legacyforhealth.org; Franciscob@etr.org NR 32 TC 2 Z9 2 U1 0 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 2012 VL 23 SU 1 BP 1 EP 5 DI 10.1007/s10552-012-9917-x PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 908AO UT WOS:000301462800001 PM 22367723 ER PT J AU Arkink, EB Bleeker, EJW Schmitz, N Schoonman, GG Wu, O Ferrari, MD van Buchem, MA van Osch, MJP Kruit, MC AF Arkink, Enrico B. Bleeker, Egbert J. W. Schmitz, Nicole Schoonman, Guus G. Wu, Ona Ferrari, Michel D. van Buchem, Mark A. van Osch, Matthias J. P. Kruit, Mark C. TI Cerebral perfusion changes in migraineurs: a voxelwise comparison of interictal dynamic susceptibility contrast MRI measurements SO CEPHALALGIA LA English DT Article DE Interictal migraine; dynamic susceptibility contrast magnetic resonance imaging; brain perfusion ID NEPHROGENIC SYSTEMIC FIBROSIS; SINGULAR-VALUE DECOMPOSITION; BRAIN-STEM ACTIVATION; HEMIPLEGIC MIGRAINE; BLOOD-FLOW; CARDIOVASCULAR-DISEASE; UNILATERAL HYPERPERFUSION; PERSISTENT AURA; HEADACHE; DIFFUSION AB Introduction: The increased risk of cerebro- and cardiovascular disease in migraineurs may be the consequence of a systemic condition affecting whole body vasculature. At cerebrovascular level, this may be reflected by interictal global or regional cerebral perfusion abnormalities. Whether focal perfusion changes occur during interictal migraine has not been convincingly demonstrated. Methods: We measured brain perfusion with dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) in 29 interictal female migraineurs (12 migraine with aura (MA), 17 migraine without aura (MO)), and 16 female controls. Perfusion maps were compared between these groups with a voxelwise (p < 0.001, uncorrected, minimum cluster size 20 voxels) and a region-of-interest approach. Results: In whole brain voxelwise analyses interictal hyperperfusion was observed in the left medial frontal gyrus in migraineurs and in the inferior and middle temporal gyrus in MO patients, in comparison with controls. Hypoperfusion was seen in the postcentral gyrus and in the inferior temporal gyrus in MA patients and in the inferior frontal gyrus in MO patients. Additional focal sites of hyperperfusion were noted in subgroups based on attack frequency and disease history. Region-of-interest analyses of the pons, hypothalamus, occipital lobe, and cerebellum did not show interictal perfusion differences between migraineurs and controls. Conclusions: We conclude that interictal migraine is characterized by discrete areas of hyper- and hypoperfusion unspecific for migraine pathophysiology and not explaining the increased vulnerability of particular brain regions for cerebrovascular damage. C1 [Arkink, Enrico B.] Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. [Wu, Ona] Massachusetts Gen Hosp, Martinos Ctr, Boston, MA 02114 USA. RP Arkink, EB (reprint author), Leiden Univ, Med Ctr, Dept Radiol, POB 9600, NL-2300 RC Leiden, Netherlands. EM e.b.arkink@lumc.nl RI Schmitz, Nicole /F-9471-2011; Kruit, Mark/K-2431-2012 OI Schmitz, Nicole /0000-0003-4178-4756; Kruit, Mark/0000-0002-4319-834X FU Dutch Brain Foundation (Nederlandse Hersenstichting) [HsN H04/08]; Dutch Technology Foundation [STW VENI 7291]; National Institutes of Health [R01 NS059775] FX This work was supported by the Dutch Brain Foundation (Nederlandse Hersenstichting, HsN H04/08) and the Dutch Technology Foundation (STW VENI 7291) and in part by grant R01 NS059775 (OW) from the National Institutes of Health. NR 50 TC 13 Z9 13 U1 2 U2 5 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD MAR PY 2012 VL 32 IS 4 BP 279 EP 288 DI 10.1177/0333102411435985 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 908UL UT WOS:000301518200004 PM 22290556 ER PT J AU Fried, L AF Fried, Linda TI Albuminuria and Cognitive Impairment SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID GLOMERULAR-FILTRATION-RATE; KIDNEY-FUNCTION; GENERAL-POPULATION; BLOOD-PRESSURE; ALL-CAUSE; DECLINE; ASSOCIATION; MORTALITY; EXCRETION; DEMENTIA C1 [Fried, Linda] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15240 USA. [Fried, Linda] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15240 USA. [Fried, Linda] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Fried, L (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Univ Dr, Pittsburgh, PA 15240 USA. EM Linda.Fried@va.gov NR 19 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2012 VL 7 IS 3 BP 376 EP 378 DI 10.2215/CJN.00210112 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 904TZ UT WOS:000301222100002 PM 22282483 ER PT J AU Ellison, DH AF Ellison, David H. TI Adaptation in Gitelman Syndrome: "We Just Want to Pump You Up" SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID NA+-CL-COTRANSPORTER; BARTTERS-SYNDROME; HYPOKALEMIC ALKALOSIS; BLOOD-PRESSURE; SALT TRANSPORT; MOUSE MODEL; CHONDROCALCINOSIS; HYPOMAGNESEMIA; MUTATIONS; HYPOCALCIURIA C1 [Ellison, David H.] Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97201 USA. [Ellison, David H.] Portland VA Med Ctr, Portland, OR USA. RP Ellison, DH (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Suite 262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM ellisond@ohsu.edu OI Ellison, David/0000-0003-2915-265X NR 25 TC 4 Z9 5 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2012 VL 7 IS 3 BP 379 EP 382 DI 10.2215/CJN.01060112 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 904TZ UT WOS:000301222100003 PM 22344514 ER PT J AU Roy-Chaudhury, P Yevzlin, A Bonventre, JV Agarwal, A Almehmi, A Besarab, A Dwyer, A Hentschel, DM Kraus, M Maya, I Pflederer, T Schon, D Wu, S Work, J AF Roy-Chaudhury, Prabir Yevzlin, Alexander Bonventre, Joseph V. Agarwal, Anil Almehmi, Ammar Besarab, Anatole Dwyer, Amy Hentschel, Dirk M. Kraus, Michael Maya, Ivan Pflederer, Timothy Schon, Donald Wu, Steven Work, Jack TI Academic Interventional Nephrology: A Model for Training, Research, and Patient Care SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HEMODIALYSIS VASCULAR ACCESS; MEDICAL-CENTERS; DIALYSIS; ANGIOPLASTY; PROGRAMS; FAILURE; GRAFT AB Dialysis vascular access dysfunction is currently a huge clinical problem. We believe that comprehensive academic-based dialysis vascular access programs that go all the way from basic and translational science investigation to clinical research to a dedicated curriculum and opportunities in vascular access for nephrologists in training are essential for improving dialysis vascular access care. This paper reviews the fundamental concepts and requirements for us to move toward this vision. Clin J Am Soc Nephrol 7: 521-524, 2012. doi: 10.2215/CJN.08360811 C1 [Roy-Chaudhury, Prabir] Univ Cincinnati, Div Nephrol, Cincinnati, OH 45267 USA. [Yevzlin, Alexander] Univ Wisconsin, Div Nephrol, Madison, WI USA. [Bonventre, Joseph V.; Hentschel, Dirk M.] Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. [Agarwal, Anil] Ohio State Univ, Div Nephrol, Columbus, OH 43210 USA. [Almehmi, Ammar] Univ Tennessee, Div Nephrol, Memphis, TN USA. [Besarab, Anatole] Henry Ford Hlth Syst, Div Nephrol, Detroit, MI USA. [Dwyer, Amy] Univ Louisville, Div Nephrol, Louisville, KY 40292 USA. [Kraus, Michael] Indiana Univ, Med Ctr, Div Nephrol, Indianapolis, IN USA. [Maya, Ivan] Nephrol Associates Cent Florida, Div Nephrol, Orlando, FL USA. [Pflederer, Timothy] Illinois Kidney Dis & Hypertens Ctr, Peoria, IL USA. [Schon, Donald] Arizona Kidney Dis & Hypertens Ctr, Phoenix, AZ USA. [Wu, Steven] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nephrol, Boston, MA USA. [Work, Jack] Emory Univ, Div Nephrol, Atlanta, GA 30322 USA. RP Roy-Chaudhury, P (reprint author), Univ Cincinnati, Div Nephrol, MSB G251,231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM roychap@ucmail.uc.edu NR 22 TC 6 Z9 6 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD MAR PY 2012 VL 7 IS 3 BP 521 EP 524 DI 10.2215/CJN.08360811 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 904TZ UT WOS:000301222100022 PM 22344507 ER PT J AU Kelly, JF Urbanoski, KA Hoeppner, BB Slaymaker, V AF Kelly, J. F. Urbanoski, K. A. Hoeppner, B. B. Slaymaker, V. TI "Ready, willing, and (not) able" to change: Young adults' response to residential treatment SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Mechanisms of change; Treatment process; Repeated measures; Young adults; Minnesota Model; Alcoholics Anonymous; 12 step ID SUBSTANCE-ABUSE TREATMENT; COGNITIVE-BEHAVIORAL TREATMENT; MULTIVARIATE PROCESS MODEL; ALCOHOL; 12-STEP; QUESTIONNAIRE; PREDICTORS; DEPENDENCE; THERAPY; METAANALYSIS AB Background: Young adulthood represents a key developmental period for the onset of substance use disorder (SUD). While the number of young adults entering treatment has increased, little is known about the mechanisms of change and early recovery processes in this important clinical population. This study investigated during-treatment change in key therapeutic processes (psychological distress, motivation, self-efficacy, coping skills, and commitment to AA/NA), and tested their relation to outcome at 3 months post-treatment. Methods: Young adults undergoing residential treatment (N = 303; age 18-24; 26% female; 95% Caucasian) were enrolled in a naturalistic prospective study and assessed at intake, mid-treatment, discharge, and 3 months following discharge. Repeated-measures and regression analyses modeled during-treatment change in process variables and impact on outcome. Results: Statistically significant medium to large effect sizes were observed for changes in most processes during treatment, with the exception of motivation, which was high at treatment intake and underwent smaller, but still significant, change. In turn, these during-treatment changes all individually predicted 3-month abstinence to varying degrees, with self-efficacy emerging as the sole predictor in a simultaneous regression. Conclusions: Findings help to clarify the mechanisms through which treatment confers recovery-related benefit among young adults. At treatment intake, high levels of abstinence motivation but lower coping, self-efficacy, and commitment to AA/NA, suggests many entering treatment may be "ready and willing" to change, but "unable" to do so without help. Treatment appears to work, in part, by helping to maintain motivation while conferring greater ability and confidence to enact such change. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Kelly, J. F.; Urbanoski, K. A.; Hoeppner, B. B.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. [Kelly, J. F.; Urbanoski, K. A.; Hoeppner, B. B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Slaymaker, V.] Hazelden Fdn Butler Ctr Res, Ctr City, MN 55012 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM jkelly11@partners.org OI Urbanoski, Karen/0000-0001-7287-7176 FU National Institute of Alcohol Abuse and Alcoholism (NIAAA) [R21AA018585]; National Institute of Drug Abuse (NIDA) [K01DA02797] FX These analyses were funded by a grant from the National Institute of Alcohol Abuse and Alcoholism (NIAAA) grant number R21AA018585 (PI: John F Kelly). Dr. Hoeppner is also supported by a grant from the National Institute of Drug Abuse (NIDA) grant number K01DA02797. Original data collection was funded by an anonymous donation to the Hazelden Foundation. NR 57 TC 15 Z9 15 U1 3 U2 22 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 2012 VL 121 IS 3 BP 224 EP 230 DI 10.1016/j.drugalcdep.2011.09.003 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 910HS UT WOS:000301628400008 PM 21955361 ER PT J AU Wan, ZM Wang, SB Kozanek, M Xia, Q Mansfield, FL Lu, GH Wood, KB Li, GA AF Wan, Zongmiao Wang, Shaobai Kozanek, Michal Xia, Qun Mansfield, Frederick L. Lu, Guohua Wood, Kirkham B. Li, Guoan TI The effect of the X-Stop implantation on intervertebral foramen, segmental spinal canal length and disc space in elderly patients with lumbar spinal stenosis SO EUROPEAN SPINE JOURNAL LA English DT Article DE Lumbar spinal stenosis; Biomechanical effect; Intervertebral foramen; Segmental spinal canal length; Intervertebral disc space ID NEUROGENIC INTERMITTENT CLAUDICATION; INTERSPINAL PROCESS DECOMPRESSION; FLEXION-EXTENSION; DISTRACTION; DEVICE AB To evaluate the biomechanical effect of the X-Stop device on the intervertebral foramen (IVF) and segmental spinal canal length (SSCL), as well as the intervertebral disc space at the implanted and the adjacent segments in patients with lumbar spinal stenosis (LSS). Eight elderly patients with LSS, scheduled for X-stop implantation, were CT or MRI scanned to construct 3D vertebral models (L2-S1). Before and after the surgery, each patient was also imaged using a dual-fluoroscopic image system during weight-bearing standing and maximum extension-flexion. The positions of the vertebrae were then determined using an established 2D-3D model matching method. The data revealed that the postoperative IVF area was significantly increased by 32.9% (or 32 mm(2)) (p < 0.05) and the IVF width was increased by 24.4% (or 1.1 mm, p = 0.06) during extension, but with minimal change in standing and flexion. The IVF heights were significantly (p < 0.05) increased at standing by 1.2 mm and extension by 1.8 mm, but not at flexion. The SSCL were significantly (p < 0.05) increased at extension by 1.2 mm, but not at standing and flexion. Anterior disc space of the implanted level was significantly decreased from 8.0 to 6.6 mm during standing. The X-Stop implantation efficiently enlarged the IVF area in the elderly patients with LSS at the operated level with little biomechanical effect immediately on the superior and inferior adjacent levels. However, it reduced the anterior disc space at the implanted level. C1 [Kozanek, Michal; Mansfield, Frederick L.; Wood, Kirkham B.; Li, Guoan] Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. [Kozanek, Michal; Mansfield, Frederick L.; Wood, Kirkham B.; Li, Guoan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wan, Zongmiao; Lu, Guohua] Second Xiangya Hosp, Dept Spinal Surg, Changsha, Hunan, Peoples R China. [Wan, Zongmiao; Lu, Guohua] Cent S Univ, Changsha, Hunan, Peoples R China. [Wang, Shaobai] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Xia, Qun] Tianjin Hosp, Dept Spinal Surg, Tianjin, Peoples R China. RP Li, GA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org FU Medtronic Inc; NIH [R21AR057989]; China Scholarship Council [2009637094] FX This study was partially supported by a research grant of Medtronic Inc, NIH (R21AR057989) and China Scholarship Council (2009637094). NR 23 TC 9 Z9 16 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0940-6719 J9 EUR SPINE J JI Eur. Spine J. PD MAR PY 2012 VL 21 IS 3 BP 400 EP 410 DI 10.1007/s00586-011-2021-1 PG 11 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 907TK UT WOS:000301441100005 PM 21935679 ER PT J AU Fazelat, A Desai, M Nandakumar, N Lowry, NC Mangoubi, R Lashkari, K AF Fazelat, Ahad Desai, Mukund Nandakumar, Namrata Lowry, Nathan C. Mangoubi, Rami Lashkari, Kameran TI Enhanced, near-infrared fundus reflectance for qualitative and quantitative analysis of subretinal lesions SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE age-related macular degeneration; ophthalmic imaging; fundus reflectance ID OCULAR FUNDUS; EYE C1 [Fazelat, Ahad; Nandakumar, Namrata; Lashkari, Kameran] Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. [Desai, Mukund; Lowry, Nathan C.; Mangoubi, Rami] Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. RP Lashkari, K (reprint author), Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. FU NIH/NIBIB [R01 EB006161-01A4]; C.S. Draper Laboratory; Schepens Eye Research Institute FX This work was supported by NIH/NIBIB grant R01 EB006161-01A4, by a C.S. Draper Laboratory internal R&D Fund (RM), and by the Stone Scholar Fund, Schepens Eye Research Institute (KL). NR 15 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAR PY 2012 VL 96 IS 1 BP 171 EP 177 DI 10.1016/j.exer.2012.01.002 PG 7 WC Ophthalmology SC Ophthalmology GA 911BU UT WOS:000301693100022 PM 22285404 ER PT J AU Reddy, MM Deshpande, A Sattler, M AF Reddy, Mamatha M. Deshpande, Anagha Sattler, Martin TI Targeting JAK2 in the therapy of myeloproliferative neoplasms SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE JAK2; metabolism; myeloproliferative neoplasms; signaling; targeted therapy ID TYROSINE KINASE JAK2; T-CELL LYMPHOMA; POLYCYTHEMIA-VERA; IN-VIVO; ERYTHROPOIETIN RECEPTOR; PRIMARY MYELOFIBROSIS; PSEUDOKINASE DOMAIN; SIGNAL-TRANSDUCTION; ACTIVATING MUTATION; CYTOKINE RECEPTORS AB Introduction: Myeloproliferative neoplasms (MPNs) are a group of stem cell diseases, including polycythemia vera, essential thrombocythemia and primary myelofibrosis. Currently, there is no curative therapy for these diseases other than bone marrow transplant; therefore there is an apparent need for palliative treatment. MPNs are frequently associated with activating mutations in JAK2; small-molecule drugs targeting this molecule have entered clinical trials. Areas covered: In this review novel JAK2 inhibitors are discussed and alternative approaches to inhibiting their transforming potential are highlighted. Current clinical approaches do not only aim at blocking JAK2 activity, but also at reducing its stability and expression are highlighted, including inhibition of heat shock protein 90 (HSP90) and deacetylases (DAC) have the potential to significantly enhance the efficacy of JAK2 inhibitors. Expert opinion: Preliminary results from clinical trials indicate the feasibility and efficacy of JAK2-targeted approaches. However, JAK2 inhibitor treatment is limited by dose-dependent toxicity and combination treatment might be required. The discovery of JAK2 mutations that cause secondary resistance in vitro would further highlight the need for the development of next-generation JAK2 inhibitors and novel synergistic approaches. C1 [Reddy, Mamatha M.; Deshpande, Anagha; Sattler, Martin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Reddy, Mamatha M.; Deshpande, Anagha; Sattler, Martin] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Reddy, Mamatha M.; Deshpande, Anagha; Sattler, Martin] Brigham & Womens Hosp, Boston, MA 02215 USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM martin_sattler@dfci.harvard.edu FU National Institutes of Health [CA134660-04] FX This work is supported in part by National Institutes of Health grant CA134660-04 to Martin Sattler. NR 96 TC 12 Z9 12 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD MAR PY 2012 VL 16 IS 3 BP 313 EP 324 DI 10.1517/14728222.2012.662956 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 907YO UT WOS:000301456700007 PM 22339244 ER PT J AU Sher, L AF Sher, Leo TI Testosterone and suicidal behavior SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Editorial Material DE aggression; cognition; depression; mood; suicide; testosterone ID VIOLENT OFFENDERS; MEN; DEPRESSION; SUPPLEMENTATION; ASSOCIATION; AGGRESSION; ATTEMPTERS; DISORDERS; MOOD C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM leo.sher@mssm.edu NR 20 TC 6 Z9 6 U1 0 U2 3 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD MAR PY 2012 VL 12 IS 3 BP 257 EP 259 DI 10.1586/ERN.12.6 PG 3 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 907CH UT WOS:000301394900002 PM 22364323 ER PT J AU Eikermann-Haerter, K Can, A Ayata, C AF Eikermann-Haerter, Katharina Can, Anil Ayata, Cenk TI Pharmacological targeting of spreading depression in migraine SO EXPERT REVIEW OF NEUROTHERAPEUTICS LA English DT Review DE animal models; hormones; ion channels; migraine; prophylaxis; spreading depression ID FAMILIAL HEMIPLEGIC MIGRAINE; GAP-JUNCTION MODULATOR; HIGH-DOSE RIBOFLAVIN; DOUBLE-BLIND; CEREBRAL-CORTEX; CORTICAL EXCITABILITY; MENSTRUAL MIGRAINE; OVARIAN HORMONES; CONTROLLED-TRIAL; HUMAN BRAIN AB Migraine, particularly with aura, is a genetically heterogeneous disorder of ion channels, pumps or transporters associated with increased cortical excitability. Spreading depression, as one reflection of hyperexcitability, is the electrophysiological event underlying aura symptoms and a trigger for headache. Endogenous (e.g., genes and hormones) and exogenous factors (e.g., drugs) modulating migraine susceptibility have also been shown to modulate spreading depression susceptibility concordantly, suggesting that spreading depression can be a relevant therapeutic target in migraine. In support of this, several migraine prophylactic drugs used in clinical practice have been shown to suppress spreading depression susceptibility as a probable mechanism of action, despite belonging to widely different pharmacological classes. Hence, susceptibility to spreading depression can be a useful preclinical model with good positive and negative predictive value for drug screening. C1 [Eikermann-Haerter, Katharina; Can, Anil; Ayata, Cenk] Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, Charlestown, MA 02129 USA. [Eikermann-Haerter, Katharina; Can, Anil; Ayata, Cenk] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Ayata, Cenk] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv & Neurosci Intens Care Unit, Boston, MA 02114 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Eikermann-Haerter, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neurovasc Res Lab, 149 13th St, Charlestown, MA 02129 USA. EM khaerter@partners.org FU NIH [NS061505]; Harvard Catalyst - The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University; American Heart Association [SDG 2610275] FX This work was in part supported by the NIH (NS061505), Harvard Catalyst - The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic healthcare centers) and American Heart Association (SDG 2610275). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 94 TC 13 Z9 13 U1 0 U2 5 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7175 J9 EXPERT REV NEUROTHER JI Expert Rev. Neurother. PD MAR PY 2012 VL 12 IS 3 BP 297 EP 306 DI 10.1586/ERN.12.13 PG 10 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 907CH UT WOS:000301394900011 PM 22364328 ER PT J AU Zhou, C Kirtane, T Tsai, TH Lee, HC Adler, DC Schmitt, J Huang, Q Fujimoto, JG Mashimo, H AF Zhou, Chao Kirtane, Tejas Tsai, Tsung-Han Lee, Hsiang-Chieh Adler, Desmond C. Schmitt, Joseph Huang, Qin Fujimoto, James G. Mashimo, Hiroshi TI Three-dimensional endoscopic optical coherence tomography imaging of cervical inlet patch SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material C1 [Zhou, Chao; Tsai, Tsung-Han; Lee, Hsiang-Chieh; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Zhou, Chao; Tsai, Tsung-Han; Lee, Hsiang-Chieh; Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Kirtane, Tejas; Huang, Qin; Mashimo, Hiroshi] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Adler, Desmond C.; Schmitt, Joseph] St Jude Med Inc, LightLab Imaging, Westford, MA USA. RP Zhou, C (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RI Zhou, Chao/A-1327-2007; OI Tsai, Tsung-Han/0000-0002-2306-2269 FU NCI NIH HHS [R01-CA75289-14, R01 CA075289]; NIBIB NIH HHS [K99 EB010071] NR 0 TC 2 Z9 2 U1 2 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 2012 VL 75 IS 3 BP 675 EP 677 DI 10.1016/j.gie.2011.11.009 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 906BM UT WOS:000301319900041 PM 22341118 ER PT J AU Boardman, CR Sonnenberg, A AF Boardman, Charles R. Sonnenberg, Amnon TI Are all colon cancers created equal? SO GASTROINTESTINAL ENDOSCOPY LA English DT Letter C1 [Boardman, Charles R.; Sonnenberg, Amnon] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Boardman, CR (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 2012 VL 75 IS 3 BP 701 EP 702 DI 10.1016/j.gie.2011.11.001 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 906BM UT WOS:000301319900055 PM 22341125 ER PT J AU Gripp, KW Lin, AE AF Gripp, Karen W. Lin, Angela E. TI Costello syndrome: a Ras/mitogen activated protein kinase pathway syndrome (rasopathy) resulting from HRAS germline mutations SO GENETICS IN MEDICINE LA English DT Review DE cancer syndrome; Costello syndrome; germline; HRAS; hypertrophic cardiomyopathy; Noonan syndrome spectrum; Ras/MAPK; rasopathy ID FACIO-CUTANEOUS SYNDROME; PHENOTYPE CORRELATION; SOMATIC MOSAICISM; GROWTH-FACTOR; ABNORMALITIES; INDIVIDUALS; DELINEATION; OVERGROWTH; DISORDERS; GENOTYPE AB Costello syndrome (OMIM# 218040) is a distinctive rare multisystern disorder comprising a characteristic coarse facial appearance, intellectual disabilities, and tumor predisposition. Although the diagnosis can be suspected clinically, confirmation requires identification of a heterozygous mutation in the proto-oncogene HRAS. In contrast to somatic oncogenic mutations in neoplasia, the Costello syndrome changes are typically introduced in the paternal germline. The predicted amino acid substitutions allow for constitutive or prolonged activation of the HRAS protein, resulting in dysregulation of the Ras/mitogen activated protein kinase pathway. Dysregulation of this signaling pathway is the disease mechanism shared among Costello syndrome and other rasopathies, including neurofibromatosis type 1, Noonan syndrome, cardio-facio-cutaneous syndrome, and Legius syndrome. The Ras/mitogen activated protein kinase pathway governs cell proliferation and differentiation, and its dysregulation affects cardiac and brain development, accounting for the significant overlap in physical and developmental differences and common medical problems among rasopathies. Unlike the genetically heterogeneous Noonan syndrome and cardio-facio-cutaneous syndrome, Costello syndrome is caused by HRAS mutations only. Patients, clinicians, and researchers may benefit from a multidisciplinary "rasopathy clinic:" which serves patients with more common conditions such as Noonan syndrome and neurofibromatosis and those affected by rare conditions such as Costello syndrome. C1 [Gripp, Karen W.] Alfred I duPont Hosp Children, Div Med Genet, Wilmington, DE USA. [Lin, Angela E.] MassGen Hosp Children, Boston, MA USA. RP Gripp, KW (reprint author), Alfred I duPont Hosp Children, Div Med Genet, Wilmington, DE USA. EM kgripp@nemours.org NR 50 TC 52 Z9 52 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAR PY 2012 VL 14 IS 3 BP 285 EP 292 DI 10.1038/GIM.0b013e31822dd91f PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 908FF UT WOS:000301475100001 PM 22261753 ER PT J AU Srivastava, MK Andersson, A Zhu, L Harris-White, M Lee, JM Dubinett, S Sharma, S AF Srivastava, Minu K. Andersson, Asa Zhu, Li Harris-White, Marni Lee, Jay M. Dubinett, Steven Sharma, Sherven TI Myeloid suppressor cells and immune modulation in lung cancer SO IMMUNOTHERAPY LA English DT Review DE APC; arginase 1; immune suppression; immune therapy; lung cancer; myeloid-derived suppressor cells; nitric oxide synthase; T lymphocytes; tumor genetic signature ID REGULATORY T-CELLS; EPITHELIAL-MESENCHYMAL TRANSITIONS; TUMOR-ASSOCIATED MACROPHAGES; ANTIGEN-PRESENTING CELLS; BONE-MARROW; DENDRITIC CELLS; GROWTH-FACTOR; IN-VIVO; CYCLOOXYGENASE-2-DEPENDENT INVASION; TRANSPLANTATION TOLERANCE AB Many tumors, including lung cancers, promote immune tolerance to escape host immune surveillance and facilitate tumor growth. Tumors utilize numerous pathways to inhibit immune responses, including the elaboration of immune-suppressive mediators such as PGE2, TGF-beta, IL-10, VEGF, GM-CSF, IL-6, S100A8/A9 and SCF, which recruit and/or activate myeloid-derived suppressor cells (MDSCs). MDSCs, a subset of heterogeneous bone marrow-derived hematopoietic cells, are found in the peripheral blood of cancer patients and positively correlate to malignancy. Solid tumors contain MDSCs that maintain an immune-suppressive network in the tumor microenvironment. This review will focus on the interaction of tumors with MDSCs that lead to dysregulation of antigen presentation and T-cell activities in murine tumor models. Specific genetic signatures in lung cancer modulate the activities of MDSCs and impact tumor progression. Targeting MDSCs may have a long-term antitumor benefit and is at the forefront of anticancer therapeutic strategies. C1 [Sharma, Sherven] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles, Los Angeles, CA USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90024 USA. EM ssharma@mednet.ucla.edu FU NCI NIH HHS [R01 CA126944-05, R01 CA126944] NR 128 TC 30 Z9 32 U1 2 U2 19 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY-UK JI Immunotherapy PD MAR PY 2012 VL 4 IS 3 BP 291 EP 304 DI 10.2217/IMT.11.178 PG 14 WC Immunology SC Immunology GA 906CI UT WOS:000301322100013 PM 22401635 ER PT J AU Ahmed, MI Desai, RV Gaddam, KK Venkatesh, BA Agarwal, S Inusah, S Lloyd, SG Denney, TS Calhoun, D Dell'italia, LJ Gupta, H AF Ahmed, Mustafa I. Desai, Ravi V. Gaddam, Krishna K. Venkatesh, Bharath A. Agarwal, Shilpi Inusah, Seidu Lloyd, Steven G. Denney, Thomas S., Jr. Calhoun, David Dell'italia, Louis J. Gupta, Himanshu TI Relation of Torsion and Myocardial Strains to LV Ejection Fraction in Hypertension SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE hypertension; left ventricular hypertrophy; strain; torsion ID HUMAN LEFT-VENTRICLE; HEART-FAILURE; HYPERTROPHY; WALL; MECHANICS; MOTION; PATTERNS; MODEL; MRI; RECONSTRUCTION AB OBJECTIVES The goal of this study was to define the mechanism of preserved ejection fraction (EF) despite depressed myocardial strains in hypertension (HTN). BACKGROUND Concentric left ventricular (LV) remodeling in HTN may have normal or supranormal EF despite depressed myocardial strains. The reason for such discordance is not clear. The aim of this study was to comprehensively evaluate the LV mechanics in a well-defined HTN population to define underlying reasons for such a paradox. METHODS Sixty-seven patients with resistant HTN and 45 healthy control subjects were studied by cardiac magnetic resonance imaging and tissue tagging with 3-dimensional analysis. Amplitude and directional vector of longitudinal (Ell), circumferential (Ecc), and principal strain for maximal shortening (E3) were computed at basal, mid, and distal LV levels, respectively. LV torsion, defined as the rotation angle of apex relative to base, and LV twist, which accounts for the effects of differential LV remodeling on torsion for comparison among the 2 groups, were also calculated. RESULTS LV mass index and LV mass/LV end-diastolic volume ratio were significantly higher in the HTN group compared with controls, consistent with concentric LV remodeling. Ell and Ecc were significantly decreased in amplitude with altered directional vector in HTN compared with controls. However, the amplitude of E3 was similar in the 2 groups. Torsion and twist were significantly higher in HTN, which was mainly due to increase in apical rotation. The HTN group demonstrated significantly increased LV wall thickening compared with controls that resulted in greater LVEF in the HTN group compared with controls (70% vs. 65%, p < 0.001, respectively). CONCLUSIONS In compensated LV remodeling secondary to HTN, there is increased LV wall thickening with preserved E3 and increased torsion compared with normal controls. This, therefore, contributes to supranormal LVEF in HTN despite depressed longitudinal and circumferential strains. (J Am Coll Cardiol lmg 2012;5:273-81) (C) 2012 by the American College of Cardiology Foundation C1 [Ahmed, Mustafa I.; Desai, Ravi V.; Gaddam, Krishna K.; Agarwal, Shilpi; Lloyd, Steven G.; Calhoun, David; Dell'italia, Louis J.; Gupta, Himanshu] Univ Alabama, Dept Med, Div Cardiovasc Med, Birmingham, AL 35294 USA. [Inusah, Seidu] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Lloyd, Steven G.; Dell'italia, Louis J.; Gupta, Himanshu] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Venkatesh, Bharath A.; Denney, Thomas S., Jr.] Auburn Univ, Dept Elect & Comp Engn, Auburn, AL 36849 USA. RP Gupta, H (reprint author), UAB Med Cardiovasc Dis, CVMRI, BDB 101,1530 3rd Ave S, Birmingham, AL 35294 USA. EM hgupta@uab.edu RI Ambale Venkatesh, Bharath/F-4941-2016 OI Ambale Venkatesh, Bharath/0000-0002-2330-2373 FU National Institutes of Health [NIH P50-HL077100, NIH R01-HL104018] FX Funded by National Institutes of Health grants NIH P50-HL077100 (L.J.D.) and NIH R01-HL104018 (H.G.). The authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 39 TC 24 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAR PY 2012 VL 5 IS 3 BP 273 EP 281 DI 10.1016/j.jcmg.2011.11.013 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 908TC UT WOS:000301513600005 PM 22421172 ER PT J AU Gurm, GS Danik, SB Shoup, TM Weise, S Takahashi, K Laferrier, S Elmaleh, DR Gewirtz, H AF Gurm, Gagandeep S. Danik, Stephan B. Shoup, Timothy M. Weise, Steven Takahashi, Kazue Laferrier, Shawna Elmaleh, David R. Gewirtz, Henry TI 4-[F-18]-Tetraphenylphosphonium as a PET Tracer for Myocardial Mitochondrial Membrane Potential SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE 4-[F-18]fluorophenyltriphenylphosphonium; mitochondrial; myocardial; positron emission tomography ID PERFUSED RAT HEARTS; POTASSIUM CHANNELS; CARDIAC WORK; CELLS; FAILURE; CARDIOPROTECTION; MALADAPTATION; ADAPTATION; MECHANISMS; DIFFUSION AB OBJECTIVES This study tested the hypothesis that 4-[F-18]fluorophenyltriphenylphosphonium (F-18-TPP) is useful for in vivo positron emission tomography (PET) measurement of mitochondrial membrane potential (Delta psi m). Its utility as a blood flow tracer also was evaluated. BACKGROUND Tetraphenylphosphonium is useful for in vitro measurement of Delta psi m. In vivo measurement of Delta psi m has potential value in the assessment of heart failure pathophysiology and therapy as well as assessment of myocardial viability and so may be a very useful clinical tool. METHODS Anesthetized swine (N = 6) with a balloon catheter in the left anterior descending coronary artery were studied. Microsphere measurements of myocardial blood flow (MBF) were made after balloon inflation (baseline) and similar to 10 min after intravenous administration of adenosine and phenylephrine after which similar to 10 mCi F-18-TPP was injected intravenously and dynamic PET data acquisition obtained for 30 min. After the swine were killed, the hearts were sectioned for microsphere measurement of MBF and F-18-TPP measured by well counter in these same samples. PET images provided whole blood and myocardial F-18-TPP concentration for determination of Delta psi m by the Nernst equation, corrected for nonspecific F-18-TPP binding. Microsphere MBF, absolute (ml/min/g) and relative, was compared with PET data (standard uptake value and K1). RESULTS Nonspecific binding of F-18-TPP overestimated Delta psi m measured by -37 +/- 4 mV (mean +/- SD). Normal zone Delta psi m of ex vivo samples (-91 +/- 11 mV; N = 52; sample weight, 1.07 +/- 0.18 g) correlated strongly (R-2 = 0.93) with normal zone by PET (-81 +/- 13 mV). Both ex vivo and PET normal zone Delta psi m although somewhat lower, compared well with that reported for tritium labeled triphenyl-phosphonium in normal working Langendorff rat heart (-100 mV). Although the relative MBF by F-18-TPP correlated strongly with relative microsphere MBF (R-2 = 0.83), there was no correlation between absolute MBF by F-18-TPP and microsphere MBF. CONCLUSIONS F-18-TPP is a promising tracer for noninvasive PET measurement of Delta psi m in living subjects. It is useful as well for assessment of relative but not absolute MBF. (J Am Coll Cardiol Img 2012;5:285-92) (C) 2012 by the American College of Cardiology Foundation C1 [Gewirtz, Henry] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med,Cardiac Unit, Boston, MA 02114 USA. [Shoup, Timothy M.; Weise, Steven; Elmaleh, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol Nucl Med Mol Imaging, Boston, MA 02114 USA. [Takahashi, Kazue] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med,Cardiac Unit, Yawkey 5E,55 Fruit St, Boston, MA 02114 USA. EM hgewirtz@partners.org FU Wild Family Foundation; FluoroPharma, Inc. FX Dr. Elmaleh is the chairman and CSO of FluoroPharma, Inc. and has received a salary from them. Dr. Goyim has received financial support from the Wild Family Foundation and FluoroPharma, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 39 TC 14 Z9 16 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAR PY 2012 VL 5 IS 3 BP 285 EP 292 DI 10.1016/j.jcmg.2011.11.017 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 908TC UT WOS:000301513600007 PM 22421174 ER PT J AU Osborn, EA Jaffer, FA AF Osborn, Eric A. Jaffer, Farouc A. TI The Year in Molecular Imaging SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE atherosclerosis; heart failure; molecular imaging; myocardial infarction; thrombosis ID EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; ABDOMINAL AORTIC-ANEURYSMS; ATHEROSCLEROTIC PLAQUES; VASCULAR INFLAMMATION; FEASIBILITY; MACROPHAGES C1 [Osborn, Eric A.; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Cardiol Div, Boston, MA 02114 USA. [Osborn, Eric A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02114 USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Jaffer, FA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Cardiol Div, Simches Res Bldg 3206,185 Cambridge St, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU National, Institutes of Health [R01 HL108229]; American Heart Association [0830352N]; Howard Hughes Medical Institute FX This study was funded by National, Institutes of Health grant R01 HL108229, American Heart Association Scientist Development Grant #0830352N, and a Howard Hughes Medical Institute Career Development Award. Dr. Jailer has received honoraria from Boston Scientific Corporation, GE Medical Systems, and Merck & Co. Dr. Osborn has reported that he has no relationships relevant to the contents of this paper to disclose. Review period: January 1-December 31, 2010. NR 26 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAR PY 2012 VL 5 IS 3 BP 317 EP 328 DI 10.1016/j.jcmg.2011.12.011 PG 12 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 908TC UT WOS:000301513600012 PM 22421179 ER PT J AU Faje, AT Tritos, NA AF Faje, Alexander T. Tritos, Nicholas A. TI Cavernous Carotid Artery Aneurysm, a Rare Cause of Intrasellar Mass and Hyperprolactinemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID INTRACRANIAL ANEURYSM C1 [Tritos, Nicholas A.] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Neuroendocrine Unit, Zero Emerson Pl,Suite 112, Boston, MA 02114 USA. EM ntritos@partners.org NR 5 TC 1 Z9 1 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2012 VL 97 IS 3 BP 723 EP 724 DI 10.1210/jc.2011-3009 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 904WM UT WOS:000301229600031 PM 22238387 ER PT J AU Kaess, BM Pedley, A Massaro, JM Larson, MG Corsini, E Hoffmann, U Smith, HM Sawyer, DB Vasan, RS Fox, CS AF Kaess, Bernhard M. Pedley, Alison Massaro, Joseph M. Larson, Martin G. Corsini, Erin Hoffmann, Udo Smith, Holly M. Sawyer, Douglas B. Vasan, Ramachandran S. Fox, Caroline S. TI Relation of Vascular Growth Factors with CT-Derived Measures of Body Fat Distribution: The Framingham Heart Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; SOLUBLE RECEPTOR SFLT-1; DISEASE RISK-FACTORS; ADIPOSE-TISSUE; GENE-EXPRESSION; BREAST-CANCER; PLASMA-LEVELS; OBESITY; ASSOCIATION; ADIPOCYTES AB Background: Visceral adiposity is associated with metabolic risk. Given that angiogenesis is a key feature of adipogenesis, variation in the association of levels of circulating vascular growth factors (and their soluble receptors) with distinct body fat compartments may explain differences in the systemic pathogenicity of regional fat depots. Methods and Results: Four body fat compartments [visceral adipose tissue (VAT), sc adipose tissue (SAT), thoracic periaortic fat, and pericardial fat] derived from computed tomography were related to serum concentrations of vascular endothelial growth factor (VEGF), the soluble VEGF receptor (fms-like tyrosine kinase-1), hepatocyte growth factor (HGF), and angiopoietin-2 and its soluble receptor (soluble tyrosine kinase with immunoglobulin-like and EGF-like domains 2 sTie-2) in 1806 Framingham Heart Study participants (mean age 44.9 yr, 44.5% women). In multivariable models, we observed positive associations between several fat compartments and VEGF and HGF levels. The magnitude of the associations were similar for VAT, SAT, and periaortic fat. We observed effect modification by sex. A stronger association was observed between VAT and HGF levels in women; higher VAT and periaortic fat were jointly associated with higher HGF concentrations (P = 0.02 and P = 0.051, respectively). In women within the highest tertile of VAT, HGF levels significantly increased with higher periaortic fat (P = 0.0005). Conclusions: In our large community-based sample, greater adiposity was associated with higher circulating growth factor levels in general. Additional studies are warranted to confirm the stronger association of VAT and periaortic fat with HGF in women and to examine its potential contribution to the sex-related differences in cardiometabolic risk. (J Clin Endocrinol Metab 97: 987-994, 2012) C1 [Kaess, Bernhard M.; Pedley, Alison; Larson, Martin G.; Vasan, Ramachandran S.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Kaess, Bernhard M.] Univ Regensburg, Dept Internal Med 2, D-93053 Regensburg, Germany. [Massaro, Joseph M.; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Dept Med, Cardiol Sect, Boston, MA 02215 USA. [Corsini, Erin; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. [Smith, Holly M.; Sawyer, Douglas B.] Vanderbilt Univ, Div Cardiovasc, Nashville, TN 37232 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU National Institutes of Health National Heart, Lung, and Blood Institute [N01-HC-25195, RO1-HL-077477] FX This work was supported by National Institutes of Health National Heart, Lung, and Blood Institute Contract N01-HC-25195 and RO1-HL-077477 (to R.S.V.). NR 48 TC 8 Z9 8 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2012 VL 97 IS 3 BP 987 EP 994 DI 10.1210/jc.2011-2310 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 904WM UT WOS:000301229600065 PM 22170711 ER PT J AU Xekouki, P Pacak, K Almeida, M Wassif, CA Rustin, P Nesterova, M Sierra, MD Matro, J Ball, E Azevedo, M Horvath, A Lyssikatos, C Quezado, M Patronas, N Ferrando, B Pasini, B Lytras, A Tolis, G Stratakis, CA AF Xekouki, Paraskevi Pacak, Karel Almeida, Madson Wassif, Christopher A. Rustin, Pierre Nesterova, Maria Sierra, Maria de la Luz Matro, Joey Ball, Evan Azevedo, Monalisa Horvath, Anelia Lyssikatos, Charalampos Quezado, Martha Patronas, Nicholas Ferrando, Barbara Pasini, Barbara Lytras, Aristides Tolis, George Stratakis, Constantine A. TI Succinate Dehydrogenase (SDH) D Subunit (SDHD) Inactivation in a Growth-Hormone-Producing Pituitary Tumor: A New Association for SDH? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CARNEY-STRATAKIS-SYNDROME; GERMLINE MUTATIONS; COMPLEX-II; HEREDITARY PARAGANGLIOMA; MOLECULAR-GENETICS; PHEOCHROMOCYTOMA; TUMORIGENESIS; EXPRESSION; VARIANTS; GENES AB Background: Mutations in the subunits B, C, and D of succinate dehydrogenase (SDH) mitochondrial complex II have been associated with the development of paragangliomas (PGL), gastrointestinal stromal tumors, papillary thyroid and renal carcinoma (SDHB), and testicular seminoma (SDHD). Aim: Our aim was to examine the possible causative link between SDHD inactivation and somatotropinoma. Patients and Methods: A 37-yr-old male presented with acromegaly and hypertension. Other family members were found with PGL. Elevated plasma and urinary levels of catecholamines led to the identification of multiple PGL in the proband in the neck, thorax, and abdomen. Adrenalectomy was performed for bilateral pheochromocytomas (PHEO). A GH-secreting macroadenoma was also found and partially removed via transsphenoidal surgery (TTS). Genetic analysis revealed a novel SDHD mutation (c.298_301delACTC), leading to a frame shift and a premature stop codon at position 133 of the protein. Loss of heterozygosity for the SDHD genetic locus was shown in the GH-secreting adenoma. Down-regulation of SDHD protein in the GH-secreting adenoma by immunoblotting and immunohistochemistry was found. A literature search identified other cases of multiple PGL and/or PHEO in association with pituitary tumors. Conclusion: We describe the first kindred with a germline SDHD pathogenic mutation, inherited PGL, and acromegaly due to a GH-producing pituitary adenoma. SDHD loss of heterozygosity, down-regulation of protein in the GH-secreting adenoma, and decreased SDH enzymatic activity supports SDHD's involvement in the pituitary tumor formation in this patient. Older cases of multiple PGL and PHEO and pituitary tumors in the literature support a possible association between SDH defects and pituitary tumorigenesis. (J Clin Endocrinol Metab 97: E357-E366, 2012) C1 [Xekouki, Paraskevi; Almeida, Madson; Nesterova, Maria; Sierra, Maria de la Luz; Ball, Evan; Azevedo, Monalisa; Horvath, Anelia; Lyssikatos, Charalampos; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Bethesda, MD 20892 USA. [Wassif, Christopher A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Dysmorphol, Bethesda, MD 20892 USA. [Pacak, Karel; Matro, Joey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. [Pacak, Karel; Matro, Joey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, Bethesda, MD 20892 USA. [Pacak, Karel; Matro, Joey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Bethesda, MD 20892 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA. [Quezado, Martha] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Patronas, Nicholas] NIH, Dept Diagnost Radiol, Clin Res Ctr, Bethesda, MD 20892 USA. [Xekouki, Paraskevi; Lytras, Aristides; Tolis, George] Hippocrate Gen Hosp, Div Endocrinol & Metab, Athens 11527, Greece. [Rustin, Pierre] INSERM, U676, Fac Med Denis Diderot, IFR02 Paris, F-75654 Paris 13, France. [Rustin, Pierre] Univ Paris 07, Fac Med Denis Diderot, IFR02 Paris, F-75221 Paris 05, France. [Ferrando, Barbara; Pasini, Barbara] Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy. [Lytras, Aristides] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02215 USA. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov OI Wassif, Christopher/0000-0002-2524-1420 FU NICHD, NIH [Z01 HD000642-04]; Agence National de la Recherche; Hellenic Endocrine Society, Athens, Greece FX This work was supported by the intramural program of the NICHD, NIH (Project Z01 HD000642-04; principal investigator C.A.S.), by the Agence National de la Recherche (Project MitOxy; principal investigator P.R.), and in part, by a 1-yr grant to P.X. on the molecular investigation of pituitary tumors by the Hellenic Endocrine Society, Athens, Greece. NR 39 TC 47 Z9 48 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2012 VL 97 IS 3 BP E357 EP E366 DI 10.1210/jc.2011-1179 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 904WM UT WOS:000301229600005 PM 22170724 ER PT J AU Brunye, TT Mahoney, CR Rapp, DN Ditman, T Taylor, HA AF Brunye, Tad T. Mahoney, Caroline R. Rapp, David N. Ditman, Tali Taylor, Holly A. TI Caffeine Enhances Real-World Language Processing: Evidence From a Proofreading Task SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-APPLIED LA English DT Article DE caffeine; arousal; language; discourse cohesion ID AUDITORY SENTENCE COMPREHENSION; RIGHT-HEMISPHERE ACTIVATION; EVENT-RELATED FMRI; TEXT COMPREHENSION; FRONTOPARIETAL NETWORK; COGNITIVE PERFORMANCE; TEMPORAL CORTEX; WORKING-MEMORY; CEREBRAL HEMISPHERES; SELECTIVE ATTENTION AB Caffeine has become the most prevalently consumed psychostimulant in the world, but its influences on daily real-world functioning are relatively unknown. The present work investigated the effects of caffeine (0 mg, 100 mg, 200 mg, 400 mg) on a commonplace language task that required readers to identify and correct 4 error types in extended discourse: simple local errors (misspelling 1- to 2-syllable words), complex local errors (misspelling 3- to 5-syllable words), simple global errors (incorrect homophones), and complex global errors (incorrect subject-verb agreement and verb tense). In 2 placebo-controlled, double-blind studies using repeated-measures designs, we found higher detection and repair rates for complex global errors, asymptoting at 200 mg in low consumers (Experiment 1) and peaking at 400 mg in high consumers (Experiment 2). In both cases, covariate analyses demonstrated that arousal state mediated the relationship between caffeine consumption and the detection and repair of complex global errors. Detection and repair rates for the other 3 error types were not affected by caffeine consumption. Taken together, we demonstrate that caffeine has differential effects on error detection and repair as a function of dose and error type, and this relationship is closely tied to caffeine's effects on subjective arousal state. These results support the notion that central nervous system stimulants may enhance global processing of language-based materials and suggest that such effects may originate in caffeine-related right hemisphere brain processes. Implications for understanding the relationships between caffeine consumption and real-world cognitive functioning are discussed. C1 [Brunye, Tad T.; Mahoney, Caroline R.] USA, NSRDEC, Cognit Sci Team, Natick, MA 01760 USA. [Brunye, Tad T.; Mahoney, Caroline R.; Ditman, Tali; Taylor, Holly A.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Rapp, David N.] Northwestern Univ, Sch Educ & Social Policy, Evanston, IL 60208 USA. [Rapp, David N.] Northwestern Univ, Dept Psychol, Evanston, IL 60208 USA. [Ditman, Tali] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Brunye, TT (reprint author), USA, NSRDEC, Cognit Sci Team, 15 Kansas St, Natick, MA 01760 USA. EM tbrunye@alumni.tufts.edu NR 148 TC 9 Z9 9 U1 4 U2 17 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1076-898X J9 J EXP PSYCHOL-APPL JI J. Exp. Psychol.-Appl. PD MAR PY 2012 VL 18 IS 1 BP 95 EP 108 DI 10.1037/a0025851 PG 14 WC Psychology, Applied SC Psychology GA 908CO UT WOS:000301468200006 PM 21988325 ER PT J AU van Leeuwen, DH Buijze, GA Ring, D AF van Leeuwen, Diederik H. Buijze, Geert A. Ring, David TI Ulnar to Radial Dorsal Fracture-Dislocations of the Wrist: A Report of 2 Cases SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article ID CARPAL DISLOCATIONS; LUNATE DISLOCATION; PERILUNATE AB This report describes 2 patients with apparent ulnar to radial dorsal fracture-dislocation: 1 had a transtriquetrum, translunate fracture dislocation and the other had a reverse stage 2 lesser arc perilunate dislocation with fracture of the ulnar styloid at its base. (J Hand Surg 2012;37A:500-502. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved) C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 9 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2012 VL 37A IS 3 BP 500 EP 502 DI 10.1016/j.jhsa.2011.12.029 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 906BY UT WOS:000301321100015 PM 22321437 ER PT J AU van Duijvenbode, DC Guitton, TG Raaymakers, EL Kloen, P Ring, D AF van Duijvenbode, Dennis C. Guitton, Thierry G. Raaymakers, Ernst L. Kloen, Peter Ring, David TI Long-Term Outcome of Isolated Diaphyseal Radius Fractures With and Without Dislocation of the Distal Radioulnar Joint SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Isolated diaphyseal radius fracture; Galeazzi fracture; distal radioulnar joint; long-term outcome ID PLATE FIXATION; GALEAZZI AB Purpose We tested the hypothesis that there are no differences between apparently isolated fractures of the radial diaphysis and isolated fractures of the radial diaphysis with concomitant dislocation of the distal radioulnar joint (DRUJ) in function, disability, and DRUJ stability more than 13 years after near-anatomic open reduction with plate and screw fixation. Methods We evaluated 17 adult patients with a diaphyseal fracture of the radius without a fracture of the ulna an average of 19 years after surgery (range, 13-33 y). Of these patients, 7 had concomitant dislocation of the DRUJ (Galeazzi fracture). At the long-term follow-up, we evaluated function with several composite scores, stability of the DRUJ, and arm-specific disability by using the Disabilities of Arm, Shoulder, and Hand questionnaire. Results The average scores were 96 (range, 85-100) on the Mayo Modified Wrist Score, 95 (range, 80-100) on the Mayo Elbow Performance Index, and 5 (range, 0-33) on the Disabilities of Arm, Shoulder, and Hand questionnaire. There were no significant differences between patients with and without DRUJ dislocation. No patients had greater laxity of the DRUJ than the opposite uninjured side. Conclusions Near-anatomic open reduction and internal fixation of diaphyseal radius fractures with and without associated DRUJ dislocation have comparable long-term results. (J Hand Surg 2012;37A:523-527. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) Type of study/level of evidence Therapeutic IV. C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, NL-1105 AZ Amsterdam, Netherlands. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org OI Guitton, Thierry/0000-0002-2599-1985 NR 15 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2012 VL 37A IS 3 BP 523 EP 527 DI 10.1016/j.jhsa.2011.11.008 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 906BY UT WOS:000301321100019 PM 22300614 ER PT J AU Ring, D Guss, D Jupiter, JB AF Ring, David Guss, Daniel Jupiter, Jesse B. TI Reconstruction of the Coronoid Process Using a Fragment of Discarded Radial Head SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Coronoid fracture; coronoid reconstruction; fracture-dislocation of the elbow; radial head fractures; traumatic elbow instability ID BONE-GRAFT; ELBOW; FRACTURES; DISLOCATION; CONTRACTURES; OLECRANON; STABILITY AB Maintaining ulnohumeral stability can be difficult when either the coronoid is too fragmented for primary repair or operative delay makes repair difficult or impossible. In addition to ligament repair, restoration of radiocapitellar contact using radial head arthroplasty, and hinged external fixation, reconstruction of the coronoid using a fragment of the discarded radial head a technique described in this report can help restore elbow stability and function. (J Hand Surg 2012;37A:570-574. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David; Guss, Daniel; Jupiter, Jesse B.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Partners Orthopaed Trauma Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Partners Orthopaed Trauma Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org FU AO Foundation; Small Bone Innovations; Wright Medical; Smith and Nephew; Biomet; Acumed; Tomier; Joint Active Systems FX Unrestricted research funding provided by AO Foundation, Small Bone Innovations, Wright Medical, Smith and Nephew, Biomet, Acumed, Tomier, and Joint Active Systems. NR 22 TC 13 Z9 16 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 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2012 VL 37A IS 3 BP 570 EP 574 DI 10.1016/j.jhsa.2011.12.016 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 906BY UT WOS:000301321100030 PM 22305734 ER PT J AU Katsnelson, A Markiewicz, MR Keith, DA Dodson, TB AF Katsnelson, Alexander Markiewicz, Michael R. Keith, David A. Dodson, Thomas B. TI Operative Management of Temporomandibular Joint Ankylosis: A Systematic Review and Meta-Analysis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MISLEADING FUNNEL PLOT; COSTOCHONDRAL GRAFT; TMJ ANKYLOSIS; FOLLOW-UP; RECONSTRUCTION; ARTHROPLASTY; REANKYLOSIS; CHILDREN; GROWTH; BIAS AB Purpose: Two common treatments of temporomandibular joint ankylosis are gap arthroplasty and ankylosis resection and reconstruction of the ramus-condyle unit with a costochondral graft. The purpose of the present study was to answer the following clinical question: "Among patients with temporomandibular joint ankylosis, do those patients who undergo gap arthroplasty, compared with those who undergo ankylosis resection and ramus-condyle unit reconstruction with a costochondral graft have better postoperative mandibular range of motion?" Methods: A systematic search of the published data was performed to identify eligible studies. The primary predictor variable was treatment type (ie, gap arthroplasty or ankylosis resection and ramuscondyle unit reconstruction). The main outcome was the change in maximal incisal opening postoperatively. A random effects model was used to compute the pooled weighted mean difference between the pre- and postoperative maximal incisal opening in both treatment groups. Results: Four studies met the inclusion criteria. Those undergoing gap arthroplasty had a significantly greater maximal incisal opening than the group undergoing ankylosis resection and ramus-condyle unit reconstruction. The weighted mean difference between the 2 groups was 2.4 mm (95% confidence interval 0.9 to 4.0; P = .002). Conclusions: Subjects with temporomandibular joint ankylosis who underwent gap arthroplasty had significantly better postoperative maximal incisal opening than those undergoing ankylosis resection and ramus-condyle unit reconstruction with a costochondral graft. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:531-536, 2012 C1 [Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Markiewicz, Michael R.] Oregon Hlth & Sci Univ, Dept Oral & Maxillofacial Surg, Portland, OR 97201 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, 55 Fruit St,Warren Bldg,Suite 1201, Boston, MA 02114 USA. EM tbdodson@partners.org FU General Hospital Department of Oral and Maxillofacial Surgery; Center for Applied Clinical Investigation; Massachusetts General Physicians Organization FX This project was supported in part by the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund (to A. Katsnelson), Center for Applied Clinical Investigation (to T. B. Dodson), and Massachusetts General Physicians Organization (to T. B. Dodson). NR 27 TC 14 Z9 15 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2012 VL 70 IS 3 BP 531 EP 536 DI 10.1016/j.joms.2011.10.003 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 908QN UT WOS:000301505300025 PM 22209104 ER PT J AU Sharaf, B Faris, CB Abukawa, H Susarla, SM Vacanti, JP Kaban, LB Troulis, MJ AF Sharaf, Basel Faris, Caroline B. Abukawa, Harutsugi Susarla, Srinivas M. Vacanti, Joseph P. Kaban, Leonard B. Troulis, Maria J. TI Three-Dimensionally Printed Polycaprolactone and beta-Tricalcium Phosphate Scaffolds for Bone Tissue Engineering: An In Vitro Study SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; POLARIZATION MICROSCOPY; MECHANICAL-PROPERTIES; DEPOSITION; DESIGN; RECONSTRUCTION; REGENERATION; OSTEOBLASTS; IMPLANTS AB Purpose: The purpose of this study was to evaluate porcine bone marrow-derived progenitor cell (pBMPC) proliferation and penetration into a novel 3-dimensionally printed scaffold. Materials and Methods: Four different tissue engineering scaffolds to evaluate pBMPC proliferation and penetration were examined. Scaffolds were fabricated from polycaprolactone (PCL) or the combination of beta-tricalcium phosphate (beta-TCP) and PCL (50: 50), with 2 separate channel sizes (1 mm [small (S)] vs 2 mm [large (L)]). Scaffolds were fabricated into 20 x 20 x 7-mm blocks by use of a TheriForm machine (Integra Life Sciences, Akron, OH). Four groups of scaffolds were examined for pBMPC proliferation and penetration: group 1, beta-TCP/PCL S; group 2, beta-TCP/PCL L; group 3, PCL S; and group 4, PCL L. Nonparametric mean (Kruskal-Wallis) and multiple comparisons tests were used to compare the 4 groups. Results: No shrinkage or deformation was noted in any of the scaffold groups after 2 weeks of culture. Mean surface cell counts ranged from 13.4 to 87.8 cells/0.57 mm(2), with group 1 (beta-TCP/PCL S) having statistically significantly higher counts than the other groups (P < .001). Mean interior cell counts ranged from 10.9 to 75.6 cells/0.57 mm(2), with group 1 having the greatest interior cell count (P < .001). Total collagen formation ranged from 0.2% to 86%, with group 1 having the highest collagen formation (P < .001). Conclusions: The 3-dimensionally printed scaffold (beta-TCP/PCL) with 1-mm channels showed greater cellular proliferation, penetration, and collagen formation after a 2-week in vitro culture than the other scaffolds evaluated. beta-TCP/PCL S scaffolds warrant further evaluation for bone tissue engineering in vivo. (c) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:647-656, 2012 C1 [Abukawa, Harutsugi; Kaban, Leonard B.; Troulis, Maria J.] Harvard Univ, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Sch Dent Med, Boston, MA 02114 USA. [Sharaf, Basel] SUNY Buffalo, Dept Surg, Buffalo Gen Hosp, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. [Faris, Caroline B.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02114 USA. [Vacanti, Joseph P.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Sch Med, Boston, MA 02114 USA. [Vacanti, Joseph P.] Harvard Univ, Massachusetts Gen Hosp, Tissue Engn & Organ Fabricat Lab, Sch Med, Boston, MA 02114 USA. RP Troulis, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Sch Dent Med, Boston, MA 02114 USA. EM mtroulis@partners.org FU Massachusetts General Hospital's Department of Oral and Maxillofacial Surgery; Hanson Foundation (Boston, MA); Massachusetts General Hospital Physicians Organization; Department of Pediatric Surgery at MassGeneral Hospital for Children FX Funded in part by the Massachusetts General Hospital's Department of Oral and Maxillofacial Surgery Education and Research Fund, the Hanson Foundation (Boston, MA), the Massachusetts General Hospital Physicians Organization, and the Department of Pediatric Surgery at MassGeneral Hospital for Children. NR 37 TC 10 Z9 10 U1 0 U2 19 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 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2012 VL 70 IS 3 BP 647 EP 656 DI 10.1016/j.joms.2011.07.029 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 908QN UT WOS:000301505300040 PM 22079064 ER PT J AU Patterson, AL Gritzner, S Resnick, MP Dobscha, SK Turk, DC Morasco, BJ AF Patterson, Alexander L. Gritzner, Susan Resnick, Michael P. Dobscha, Steven K. Turk, Dennis C. Morasco, Benjamin J. TI Smoking Cigarettes as a Coping Strategy for Chronic Pain Is Associated With Greater Pain Intensity and Poorer Pain-Related Function SO JOURNAL OF PAIN LA English DT Article DE Smoking; cigarettes; chronic pain; coping ID LOW-BACK-PAIN; NICOTINE DEPENDENCE; PROSPECTIVE COHORT; POPULATION SAMPLE; FOLLOW-UP; PREDICTORS; INVENTORY; ANXIETY; ADULTS; RISK AB Smoking cigarettes is prevalent among individuals with chronic pain. Some studies indicate nicotine reduces pain and others suggest it may cause or exacerbate pain. Participants in this cross-sectional study were 151 chronic pain patients from a large, urban VA medical center. Patients were divided into 3 groups: 1) nonsmokers; 2) smokers who deny using cigarettes to cope with pain; and 3) smokers who report using cigarettes to cope with pain. Patients who reported smoking as a coping strategy for chronic pain scored significantly worse compared with the other 2 groups on the majority of measures of pain-related outcome. Nonsmokers and smokers who denied smoking to cope did not differ on any variable examined. After controlling for the effects of demographic and clinical factors, smoking cigarettes as a coping strategy for pain was significantly and positively associated with pain intensity (P = .04), pain interference (P = .005), and fear of pain (P = .04). In addition to assessing general smoking status, a more specific assessment of the chronic pain patient's reasons for smoking may be an important consideration as part of interdisciplinary pain treatment. Perspective: This paper describes the relationship between smoking cigarettes as a mechanism to cope with chronic pain and pain-related outcome. Understanding this relationship may illuminate the broader relationship between smoking and chronic pain and provide new directions for effective interdisciplinary pain treatment. C1 [Patterson, Alexander L.; Resnick, Michael P.; Dobscha, Steven K.; Morasco, Benjamin J.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR USA. [Dobscha, Steven K.] Portland VA Med Ctr, Ctr Study Chron Comorbid Med & Psychiat Disorders, Portland, OR USA. [Gritzner, Susan; Resnick, Michael P.; Dobscha, Steven K.; Morasco, Benjamin J.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Gritzner, Susan] Univ Pacific, Sch Profess Psychol, Hillsboro, OR USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Morasco, BJ (reprint author), Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR USA. EM benjamin.morasco@va.gov FU Portland VA Medical Center; National Institute on Drug Abuse [K23DA023467]; Endo; Johnson Johnson; Philips Respironics; National Institutes of Health; Eli Lilly; Empi; Pfizer; SK LifeScience FX This work was supported with resources and the use of facilities at the Portland VA Medical Center. This study was funded by grant K23DA023467 from the National Institute on Drug Abuse, awarded to Dr. Morasco. Dr. Turk has received research support from Endo, Johnson & Johnson, Philips Respironics, and the National Institutes of Health, and consulting fees from Eli Lilly, Empi, Johnson & Johnson, Pfizer, Philips Respironics, and SK LifeScience. NR 57 TC 30 Z9 30 U1 0 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD MAR PY 2012 VL 13 IS 3 BP 285 EP 292 DI 10.1016/j.jpain.2011.11.008 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 910BT UT WOS:000301612900009 PM 22325299 ER PT J AU Olcese, ME Mack, JW AF Olcese, Maura E. Mack, Jennifer W. TI Research Participation Experiences of Parents of Children with Cancer Who Were Asked about their Child's Prognosis SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID BEREAVED PARENTS; COMMUNICATION; QUESTIONNAIRE; PERCEPTIONS; PREFERENCES; DISCLOSURE; COLLUSION; PATIENT; DEATH; HOPE AB Background: In questionnaire-based research, human subject protection committees must assess the emotional impact of the study on participants. Without clear data about the risks and benefits of participating in such studies, however, review board members must use personal judgment to assess emotional harm. Objective: To examine experiences of distress and value of participation in a study of prognosis communication among parents of children with cancer, and to identify factors associated with predominantly distressing research experiences. Methods: We surveyed 194 parents of children with cancer (overall response rate, 70%), treated at the Dana-Farber Cancer Institute and Children's Hospital, Boston, Mass, in the first year after the child's cancer diagnosis. The survey focused on the child's prognosis and parent-physician communication; at the end, we asked parents how distressing and how useful completing the survey had been to them personally. Results: Only 1% of parents found research participation to be "very" distressing. The majority of parents were "not at all" distressed by participating (62%), and most reported that the questionnaire was at least "a little" useful to them personally (69%). Overall, 18% of parents gave higher ratings for distress than for utility. Parents were more likely to experience research participation as predominantly distressing when they found prognostic information to be upsetting (odds ratio [OR] 5.38, p = 0.005). Conclusion: Most participating parents were able to respond to questions about their child's prognosis with little or no distress. Even when distress was present, it was often accompanied by a perception that participating was of value. C1 [Olcese, Maura E.; Mack, Jennifer W.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Olcese, Maura E.; Mack, Jennifer W.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Mack, Jennifer W.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Mack, JW (reprint author), Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Smith 273, Boston, MA 02115 USA. EM Jennifer_mack@dfci.harvard.edu FU Agency for Healthcare Research and Quality [T32 HS00063]; American Society of Clinical Oncology; Glaser Pediatric Research Network FX Dr. Mack was supported by a fellowship from the Agency for Healthcare Research and Quality (T32 HS00063), an American Society of Clinical Oncology Young Investigator Award, and a fellowship from the Glaser Pediatric Research Network. NR 30 TC 3 Z9 3 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 J9 J PALLIAT MED JI J. Palliat. Med. PD MAR PY 2012 VL 15 IS 3 BP 269 EP 273 DI 10.1089/jpm.2011.0304 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 906OG UT WOS:000301354800005 PM 22339249 ER PT J AU Goldstein, NE Cohen, LM Arnold, RM Goy, E Arons, S Ganzini, L AF Goldstein, Nathan E. Cohen, Lewis M. Arnold, Robert M. Goy, Elizabeth Arons, Stephen Ganzini, Linda TI Prevalence of Formal Accusations of Murder and Euthanasia against Physicians SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID ASSISTED SUICIDE; UNITED-STATES; PATIENT CHARACTERISTICS; PALLIATIVE CARE; CANCER-PATIENTS; LIFE; END; POPULATION; SURVIVAL; OREGON AB Background: Little is known about how often physicians are formally accused of hastening patient deaths while practicing palliative care. Methods: We conducted an Internet-based survey on a random 50% sample of physician-members of a national hospice and palliative medicine society. Results: The final sample consisted of 663 physicians (response rate 53%). Over half of the respondents had had at least one experience in the last 5 years in which a patient's family, another physician, or another health care professional had characterized palliative treatments as being euthanasia, murder, or killing. One in four stated that at least one friend or family member, or a patient had similarly characterized their treatments. Respondents rated palliative sedation and stopping artificial hydration/nutrition as treatments most likely to be misconstrued as euthanasia. Overall, 25 physicians (4%) had been formally investigated for hastening a patient's death when that had not been their intention-13 while using opiates for symptom relief and six for using medications while discontinuing mechanical ventilation. In eight (32%) cases, another member of the health care team had initiated the charges. At the time of the survey, none had been found guilty, but they reported experiencing substantial anger and worry. Conclusions: Commonly used palliative care practices continue to be misconstrued as euthanasia or murder, despite this not being the intention of the treating physician. Further efforts are needed to explain to the health care community and the public that treatments often used to relieve patient suffering at the end of life are ethical and legal. C1 [Goldstein, Nathan E.] Mt Sinai Med Ctr, Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Goldstein, Nathan E.] James J Peters VA Med Ctr, Bronx, NY USA. [Cohen, Lewis M.] Baystate Med Ctr, Dept Psychiat, Springfield, MA USA. [Arnold, Robert M.] Univ Pittsburgh, Div Gen Internal Med, Sch Hlth Sci, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. [Goy, Elizabeth; Ganzini, Linda] Portland VA Med Ctr, Portland, OR USA. [Goy, Elizabeth; Ganzini, Linda] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Arons, Stephen] Univ Massachusetts, Dept Legal Studies, Amherst, MA 01003 USA. RP Goldstein, NE (reprint author), Mt Sinai Med Ctr, Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, Box 1070,1 Gustave Levy Pl, New York, NY 10029 USA. EM Nathan.Goldstein@mssm.edu FU National Institute on Aging [1K23 AG025933-01A1]; Greenwall Foundation FX The authors would like to thank the physicians who participated in our survey. This work was supported in part by a grant from the Greenwall Foundation. Dr. Goldstein is supported by a Mentored Patient-Oriented Research Career Development Award from the National Institute on Aging (1K23 AG025933-01A1). Drs. Ganzini and Goy received support through the use of resources and facilities at the Portland VAMC. Portions of these data were presented at the Annual Assembly of the American Association of Hospice and Palliative Medicine in Vancouver, BC, in February 2011. Drs. Goldstein, Cohen, Arnold, and Ganzini had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 19 TC 14 Z9 14 U1 0 U2 15 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAR PY 2012 VL 15 IS 3 BP 334 EP 339 DI 10.1089/jpm.2011.0234 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 906OG UT WOS:000301354800016 PM 22401355 ER PT J AU Vallurupalli, M Vesel, T AF Vallurupalli, Mounica Vesel, Tamara TI Hidden Suffering SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 [Vallurupalli, Mounica; Vesel, Tamara] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Vesel, T (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Pediat Palliat Care, 44 Binney St, Boston, MA 02115 USA. EM tamara_vesel@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAR PY 2012 VL 15 IS 3 BP 362 EP 363 DI 10.1089/jpm.2011.0309 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 906OG UT WOS:000301354800022 PM 22401360 ER PT J AU Nelson, K Vesel, T AF Nelson, Katherine Vesel, Tamara TI Redefining Success SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material C1 [Vesel, Tamara] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Pediat Palliat Care, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Vesel, T (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Div Pediat Palliat Care, 44 Binney St, Boston, MA 02115 USA. EM tamara_vesel@dfci.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD MAR PY 2012 VL 15 IS 3 BP 368 EP 369 DI 10.1089/jpm.2011.0385 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 906OG UT WOS:000301354800024 PM 22401363 ER PT J AU Nagykaldi, Z Aspy, CB Chou, A Mold, JW AF Nagykaldi, Zsolt Aspy, Cheryl B. Chou, Ann Mold, James W. TI Impact of a Wellness Portal on the Delivery of Patient-Centered Preventive Care SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Community Medicine; Computers; Evidence-Based Medicine; Medical Decision-Making; Patient-Centered Care; Personal Health Records; Practice-Based Research; Primary Health Care; Prevention; Wellness Portal ID ACTIVATION MEASURE; UNITED-STATES; QUALITY; TIME AB Background: The objective of this study was to determine the impact of the Wellness Portal-a novel, web-based patient portal that focuses on wellness, prevention, and longitudinal health-on the delivery of patient-centered preventive care by examining the behavior and experiences of both patients and primary care clinicians and the degree to which recommended services were individualized and provided. Methods: We conducted a 3-year, systematic portal development and testing study, which included a 6-month feasibility and acceptability pilot in 2 primary care practices followed by a 12-month cluster randomized controlled trial in 8 clinician practices (4 in each study group). Descriptive and bivariate analyses were conducted to compare service delivery between intervention and control arms. Results: Ninety percent of patients in the pilot study found the portal easy to use, 83% found it to be a valuable resource, and 80% said that it facilitated their participation in their own care. The cluster randomized controlled trial included 422 adults 40 to 75 years of age and the parents of 116 children 2 to 5 years of age. Seventy three percent of patients used the portal during the study. Both patient activation (measured via the 13-item Patient Activation Measure) and participants' perception of patient-centeredness of care (measured via the Consumer Assessment of Healthcare Providers and Systems instrument) increased significantly in the portal group compared with control (P = .0014 and P = .037, respectively). A greater proportion of portal users received all recommended preventive services (84.4% intervention vs 67.6% control; P < .0001); took low-dose aspirin, if indicated (78.6% intervention vs 52.3% control; P < .0001); and received Pneumovax because of chronic health conditions (82.5% vs 53.9%; P < .0001) and age (86.3% vs 44.6%; P < .0001), despite having fewer visits over the study period compared with those in the control group (average of 2.9 vs 4.3 visits; P < .0001). Children in the intervention group received 95.5% of all recommended immunizations compared with 87.2% in the control group (P = .044). Conclusions: A comprehensive patient portal integrated into the regular process of primary care can increase the patient-centeredness of care, improve patient activation, enhance the delivery of both age- and risk factor-appropriate preventive services, and promote the utilization of web-based personal health records. (J Am Board Fam Med 2012;25:158-167.) C1 [Nagykaldi, Zsolt; Aspy, Cheryl B.; Mold, James W.] Univ Oklahoma, Hlth Sci Ctr, Dept Family & Prevent Med, Oklahoma City, OK 73104 USA. [Chou, Ann] Greater Los Angeles VA Hlth Care Syst, Vet Affairs Hlth Serv Res & Dev, Ctr Excellence Study Healthcare Provider Behav, Los Angeles, CA USA. RP Nagykaldi, Z (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Family & Prevent Med, 900 NE 10th St, Oklahoma City, OK 73104 USA. EM znagykal@ouhsc.edu FU Agency for Healthcare Research and Quality [1 R18 HS017188-01] FX Support for this study was provided by the Agency for Healthcare Research and Quality grant no. 1 R18 HS017188-01. NR 15 TC 25 Z9 25 U1 2 U2 20 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD MAR-APR PY 2012 VL 25 IS 2 BP 158 EP 167 DI 10.3122/jabfm.2012.02.110130 PG 10 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 905VN UT WOS:000301304300006 PM 22403196 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Pre-Judging Data: Benchmarking Clinical Significance Before Study Results Are Known SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. EM burstein@nccn.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2012 VL 10 IS 3 BP 289 EP 290 PG 2 WC Oncology SC Oncology GA 904UB UT WOS:000301222300001 PM 22393189 ER PT J AU Pfister, DG Ang, KK Brizel, DM Burtness, B Cmelak, AJ Colevas, AD Dunphy, F Eisele, DW Gilbert, J Gillison, ML Haddad, RI Haughey, BH Hicks, WL Hitchcock, YJ Kies, MS Lydiatt, WM Maghami, E Martins, R McCaffrey, T Mittal, BB Pinto, HA Ridge, JA Samant, S Sanguineti, G Schuller, DE AF Pfister, David G. Ang, Kie-Kian Brizel, David M. Burtness, Barbara Cmelak, Anthony J. Dimitrios Colevas, A. Dunphy, Frank Eisele, David W. Gilbert, Jill Gillison, Maura L. Haddad, Robert I. Haughey, Bruce H. Hicks, Wesley L. Hitchcock, Ying J. Kies, Merrill S. Lydiatt, William M. Maghami, Ellie Martins, Renato McCaffrey, Thomas Mittal, Bharat B. Pinto, Harlan A. Ridge, John A. Samant, Sandeep Sanguineti, Giuseppe Schuller, David E. TI Mucosal Melanoma of the Head and Neck SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review DE NCCN Clinical Practice Guidelines; NCCN Guidelines; mucosal melanoma; head and neck cancer; biopsy; neck dissection; adjuvant therapy; radiation therapy; chemotherapy; pathology ID POSTOPERATIVE RADIOTHERAPY; RADIATION-THERAPY; METASTATIC MELANOMA; CO-MORBIDITY; MALIGNANT-MELANOMA; SINONASAL MELANOMA; CUTANEOUS MELANOMA; COMORBIDITY INDEX; KIT MUTATION; CANCER C1 [Ang, Kie-Kian; Kies, Merrill S.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Burtness, Barbara; Ridge, John A.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Gillison, Maura L.; Schuller, David E.] Ohio State Univ, James Canc Hosp, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Haddad, Robert I.] Massachusetts Gen Hosp, Ctr Canc, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02114 USA. [Haughey, Bruce H.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Haughey, Bruce H.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Hicks, Wesley L.] Roswell Pk Canc Inst, Buffalo, NY USA. [Hitchcock, Ying J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [McCaffrey, Thomas] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Samant, Sandeep] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. OI Shah, Jatin/0000-0002-6444-6592 NR 57 TC 11 Z9 12 U1 1 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2012 VL 10 IS 3 BP 320 EP 338 PG 19 WC Oncology SC Oncology GA 904UB UT WOS:000301222300006 PM 22393194 ER PT J AU Habito, CMR Kalva, SP AF Habito, Cicero Matthew R. Kalva, Sanjeeva P. TI Partial Anomalous Pulmonary Venous Return Detected Incidentally during Port Placement SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material C1 [Habito, Cicero Matthew R.] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Habito, CMR (reprint author), Massachusetts Gen Hosp, Dept Imaging, 55 Fruit St,WHT 427, Boston, MA 02114 USA. EM chabito@partners.org NR 2 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR PY 2012 VL 23 IS 3 BP 369 EP 369 DI 10.1016/j.jvir.2011.11.011 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 906EQ UT WOS:000301328100016 PM 22277274 ER PT J AU McDermott, S Hedgire, SS Hahn, PF Mueller, PR Harisinghani, MG AF McDermott, Shaunagh Hedgire, Sandeep S. Hahn, Peter F. Mueller, Peter R. Harisinghani, Mukesh G. TI Image-guided Biopsy of Suspicious Lymph Nodes in Patients with Known Primary Malignancies SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID CORE-NEEDLE-BIOPSY; CANCER-PATIENTS; BREAST-CANCER; BONE-BIOPSY; METASTASES; DIAGNOSIS; LESIONS; SENSITIVITY AB Purpose: To determine how often abdominal, pelvic, and inguinal lymphadenopathy in patients with a known malignancy arises from a second primary cancer or from benign causes, rather than from the cancer already known. Material and Methods: A total of 196 patients with a history of a single biopsy-proven malignancy underwent image-guided abdominal or pelvic lymph node (LN) biopsies between January 2000 and January 2005. Three patients were excluded. The medical records and imaging of the remaining 193 patients were reviewed. Pathologic results were assigned to one of three outcomes: LN involvement by known malignancy, newly diagnosed malignancy, or no malignancy identified. Patients in whom malignancy was not identified required repeat biopsy or stability or reduction in size of LN on follow-up imaging for confirmation while not receiving treatment. Results: Of the 193 included biopsies, there was LN involvement by the known malignancy in 148 (76.7%; 95% CI, 70.1%-82.5%), a newly diagnosed malignancy in 19 (9.8%; 95% CI, 6.0%-14.9%), and no malignancy identified in 26 (13.5%; 95% CI, 9.0%-19.1%). Conclusions: Biopsy of a suspicious abdominal or pelvic LN in patients with known malignancy reveals a newly diagnosed malignancy or no evidence of malignancy in 23% of cases, emphasizing the importance of biopsy. C1 [McDermott, Shaunagh; Hedgire, Sandeep S.; Hahn, Peter F.; Mueller, Peter R.; Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP McDermott, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,Room 270, Boston, MA 02114 USA. EM smodermott1@partners.org NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR PY 2012 VL 23 IS 3 BP 371 EP 376 DI 10.1016/j.jvir.2011.11.028 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 906EQ UT WOS:000301328100017 PM 22265244 ER PT J AU Geueke, A Morley, MG Morley, K Lorch, A Jackson, M Lambrou, A Wenberg, J Oteng-Amoako, A AF Geueke, Anna Morley, Michael G. Morley, Katharine Lorch, Alice Jackson, MaryLou Lambrou, Angeliki Wenberg, June Oteng-Amoako, Afua TI Anxiety and Charles Bonnet Syndrome SO JOURNAL OF VISUAL IMPAIRMENT & BLINDNESS LA English DT Article ID VISUAL HALLUCINATIONS; STATE AB Introduction: Some persons with Charles Bonnet syndrome (CBS) suffer significant anxiety because of their visual hallucinations, while others do not. The aim of the study presented here was to compare levels of anxiety in persons with low vision with and without CBS. Methods: This retrospective study compared the level of anxiety in 31 persons with CBS and 26 persons without CBS. These participants were recruited voluntarily from senior centers, a low vision support group, and an ophthalmology practice in October and November 2010. All were administered surveys to measure cognitive function (TICS: Telephone Interview for Cognitive Status), anxiety (STAI: State and Trait Anxiety Inventory), and general health (GHQ: General Health Questionnaire). The responses of the two groups were compared. Results: The participants with CBS exhibited higher levels of anxiety than did those without CBS on both the STAI and GHQ surveys, but this difference did not reach statistical significance. The proportion of participants who were pharmacologically treated for anxiety was four times higher in the CBS cohort than in the cohort without CBS: CBS: 36% (11 of 31), those without CBS: 9% (2 of 22), p value = .03. The participants with CBS who took medication for anxiety scored higher on the STAI and GHQ than did those without CBS, but these differences did not reach statistical significance. Discussion: The findings indicate that persons with CBS have higher levels of anxiety than do those without CBS. The highest levels of anxiety occurred in the participants with CBS who were being treated for anxiety with medications. Although the findings did not reach statistical significance, they suggest that anxiety is an important consideration when treating individuals with CBS. Implications for practitioners: Persons with CBS who have difficulty tolerating visual hallucinations may benefit from interventions that are directed at managing anxiety, such as counseling, visual rehabilitation, and pharmacological treatment. C1 [Morley, Michael G.] Ctr Eye Res & Educ, Boston, MA 02114 USA. [Morley, Katharine] Harvard Univ, Sch Med, Newton, MA 02458 USA. [Jackson, MaryLou] Massachusetts Eye & Ear Infirm, Vis Rehabil Ctr, Boston, MA 02114 USA. [Oteng-Amoako, Afua] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wenberg, June] Sight Loss Serv, W Dennis, MA 02670 USA. [Geueke, Anna] Univ Massachusetts, Sch Nursing, Worcester, MA 01605 USA. RP Lorch, A (reprint author), 37 Lee St,Apartment 3, Cambridge, MA 02139 USA. EM anna.getteke@gmail.com; mgmorley@gmail.com; katharinemorley@gmail.com; alice_lorch@meei.harvard.edu; marylou@mljackson.ca; alambrou@hsph.harvard.edu; jscully@jwen.com; afuaamoako@gmail.com NR 16 TC 1 Z9 1 U1 0 U2 8 PU AMER FOUNDATION BLIND PI NEW YORK PA J VISUAL IMPAIRMENT BLINDNESS 2 PENN PLAZA, SUITE 1102, NEW YORK, NY 10121 USA SN 0145-482X J9 J VISUAL IMPAIR BLIN JI J. Vis. Impair. Blind. PD MAR PY 2012 VL 106 IS 3 BP 145 EP 153 PG 9 WC Rehabilitation SC Rehabilitation GA 910XC UT WOS:000301680900003 ER PT J AU Izikson, L AF Izikson, Leonid TI DOUBLE vs SINGLE TREATMENT OF TATTOOS WITH A PICOSECOND AND NANOSECOND LASER IN THE SAME SESSION: A PILOT CLINICAL STUDY SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Izikson, Leonid] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2012 VL 44 SU 24 BP 6 EP 6 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 909OE UT WOS:000301573200018 ER PT J AU Lewis, WF Farinelli, WA Doukas, A Anderson, RR Sakamoto, FH AF Lewis, William F. Farinelli, William A. Doukas, Apostolos Anderson, R. Rox Sakamoto, Fernanda H. TI SELECTIVE PHOTOTHERMOLYSIS OF SEBACEOUS GLANDS - A PRELIMINARY STUDY USING TWO NEAR INFRA-RED PROTOTYPE LASERS SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Lewis, William F.; Farinelli, William A.; Doukas, Apostolos; Anderson, R. Rox; Sakamoto, Fernanda H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2012 VL 44 SU 24 BP 8 EP 9 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA 909OE UT WOS:000301573200024 ER PT J AU Sakamoto, FH Izikson, L Lewis, W Ferrick, B Doukas, A Farinelli, WA Ibrahimi, O Tannous, Z Anderson, RR Zurakowski, D AF Sakamoto, Fernanda H. Izikson, Leonid Lewis, William Ferrick, Bradford Doukas, Apostolos Farinelli, William A. Ibrahimi, Omar Tannous, Zeina Anderson, R. Rox Zurakowski, David TI PRELIMINARY RESULTS OF A PILOT PROSPECTIVE RAMDOMIZED DOUBLE-BLINDED CONTROL STUDY TO COMPARE A NEW INHIBITORY PDT METHOD TO CONVENTIONAL ALA-PDT FOR THE TREATMENT OF RECALCITRANT MODERATE-SEVERE ACNE SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2012 VL 44 SU 24 BP 8 EP 8 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 909OE UT WOS:000301573200023 ER PT J AU Vacas-Jacques, P Williams, M Jimenez-Lozano, J Fahlman, A Moore, M Tyack, P Zapol, W Anderson, R Franco, W AF Vacas-Jacques, Paulino Williams, Maura Jimenez-Lozano, Joel Fahlman, Andreas Moore, Michael Tyack, Peter Zapol, Warren Anderson, Rox Franco, Walfre TI DEVELOPMENT AND VALIDATION OF A PHYSIOLOGICAL TAG FOR MONITORING OXYGEN SATURATION IN MUSCLE OF FREE-DIVING WHALES SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Texas A&M Univ, Corpus Christi, TX USA. Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. Univ St Andrews, Sch Biol, St Andrews, Fife, Scotland. RI Tyack, Peter/D-6209-2013; Fahlman, Andreas/A-2901-2011; Moore, Michael/E-1707-2015 OI Tyack, Peter/0000-0002-8409-4790; Fahlman, Andreas/0000-0002-8675-6479; Moore, Michael/0000-0003-3074-6631 NR 0 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2012 VL 44 SU 24 BP 30 EP 31 PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA 909OE UT WOS:000301573200086 ER PT J AU Yaroslavsky, A Joseph, C Neel, V Goyette, T Giles, R Patel, R AF Yaroslavsky, Anna Joseph, Cecil Neel, Victor Goyette, Thomas Giles, Robert Patel, Rakesh TI DELINEATING NONMELANOMA SKIN CANCERS USING OPTICAL AND TERAHERTZ IMAGING SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Univ Massachusetts, Adv Biophoton Lab, Lowell, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2012 VL 44 SU 24 BP 36 EP 36 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 909OE UT WOS:000301573200103 ER PT J AU Carroll, J Khuman, J Zhang, J Park, J Donahue, C Whalen, M AF Carroll, James Khuman, Jugta Zhang, Jimmy Park, Juyeon Donahue, Chad Whalen, Michael TI LOW-LEVEL LASER LIGHT THERAPY IMPROVES COGNITIVE DEFICITS AND INHIBITS MICROGLIAL ACTIVATION AFTER CONTROLLED CORTICAL IMPACT IN MICE SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. THOR Photomed Ltd, Chesham, Bucks, England. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2012 VL 44 SU 24 BP 50 EP 50 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 909OE UT WOS:000301573200144 ER PT J AU Wang, ZH Bordas, V Sagotsky, J Deisboeck, TS AF Wang, Zhihui Bordas, Veronika Sagotsky, Jonathan Deisboeck, Thomas S. TI Identifying therapeutic targets in a combined EGFR-TGF beta R signalling cascade using a multiscale agent-based cancer model SO MATHEMATICAL MEDICINE AND BIOLOGY-A JOURNAL OF THE IMA LA English DT Article DE agent-based model; multiscale; non-small cell lung cancer; epidermal growth factor receptor; transforming growth factor beta; signalling pathway ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; FACTOR RECEPTOR INHIBITORS; SENSITIVITY-ANALYSIS; FUTURE-DIRECTIONS; CROSS-SCALE; GEFITINIB; ERLOTINIB; ONCOLOGY; PATHWAY AB Applying a previously developed non-small cell lung cancer model, we assess 'cross-scale' the therapeutic efficacy of targeting a variety of molecular components of the epidermal growth factor receptor (EGFR) signalling pathway. Simulation of therapeutic inhibition and amplification allows for the ranking of the implemented downstream EGFR signalling molecules according to their therapeutic values or indices. Analysis identifies mitogen-activated protein kinase and extracellular signal-regulated kinase as top therapeutic targets for both inhibition and amplification-based treatment regimen but indicates that combined parameter perturbations do not necessarily improve the therapeutic effect of the separate parameter treatments as much as might be expected. Potential future strategies using this in silico model to tailor molecular treatment regimen are discussed. C1 [Wang, Zhihui; Sagotsky, Jonathan; Deisboeck, Thomas S.] Massachusetts Gen Hosp East, Complex Biosyst Modeling Lab, Harvard HST Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Bordas, Veronika] Harvard Univ, Dept Appl Math, Cambridge, MA 02138 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp East, Complex Biosyst Modeling Lab, Harvard HST Athinoula A Martinos Ctr Biomed Imagi, 2301 Bldg 149,13th St, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu FU National Institutes of Health [CA 113004]; Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging; Department of Radiology at Massachusetts General Hospital FX This work has been supported in part by the National Institutes of Health (grant CA 113004) and by the Harvard-MIT (HST) Athinoula A. Martinos Center for Biomedical Imaging and the Department of Radiology at Massachusetts General Hospital. NR 26 TC 13 Z9 13 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1477-8599 J9 MATH MED BIOL JI Math. Med. Biol. PD MAR PY 2012 VL 29 IS 1 SI SI BP 95 EP 108 DI 10.1093/imammb/dqq023 PG 14 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 905UN UT WOS:000301301100008 PM 21147846 ER PT J AU Weil, AA Baron, EL Brown, CM Drapkin, MS AF Weil, Ana A. Baron, Elinor L. Brown, Catherine M. Drapkin, Mark S. TI Clinical Findings and Diagnosis in Human Granulocytic Anaplasmosis: A Case Series From Massachusetts SO MAYO CLINIC PROCEEDINGS LA English DT Article ID UNITED-STATES; LYME-DISEASE; EHRLICHIOSIS; PHAGOCYTOPHILUM; RESIDENTS; SEROPREVALENCE; EPIDEMIOLOGY; BEHAVIORS; WISCONSIN; MAINE AB Objective: To describe clinical findings and the use of a tick-associated pathogen panel in a series of patients with human granulocytic anaplasmosis (HGA) at a suburban Boston hospital. Patients and Methods: Medical records were reviewed for inpatients and outpatients at Newton-Wellesley Hospital with a positive polymerase chain reaction (PCR) result for Anaplasma phagocytophilum during the study period March 1 through November 30, 2009. A PCR panel was used to test for tick-borne pathogens. Postal zip code data from the patients' areas of residence were used to estimate the area of disease transmission. Results: Thirty-three cases were confirmed during the 2009 transmission season, and 14 of these patients (42%) required hospitalization. Thrombocytopenia and/or leukopenia were observed at the time of presentation in 25 of 30 patients (86%) in whom both white blood cell and platelet counts were determined, and 28 of 33 patients (85%) reported fever. Rash occurred in only 2 of the 33 patients (6%), and 25 (76%) reported one or more respiratory or gastrointestinal symptom. Cases were geographically distributed diffusely throughout the hospital catchment area, with one possible focus of infection identified in Weston, MA. Due to a lack of clinical data reporting to the Massachusetts Department of Public Health, only 20 of 32 HGA cases (63%) fulfilled the case confirmation criteria. Conclusion: Diagnosis of HGA requires a high suspicion for infection even in endemic areas. Use of a tick-associated pathogen panel that includes PCR assays for several organisms could improve detection of underrecognized tick-borne diseases in endemic areas. Lack of epidemiological follow-up to confirm corroborating clinical findings prevents accurate case reporting and assessment of the true HGA burden. (C) 2012 Mayo Foundation for Medical Education and Research square Mayo Clin Proc. 2012;87(3):233-239 C1 [Weil, Ana A.] Massachusetts Gen Hosp, Dept Med, Wang Ambulatory Care Ctr 645, Boston, MA 02114 USA. [Baron, Elinor L.; Drapkin, Mark S.] Newton Wellesley Hosp, Infect Dis Serv, Newton Lower Falls, MA 02162 USA. [Baron, Elinor L.; Drapkin, Mark S.] Tufts Univ, Sch Med, Div Geog Med & Infect Dis, Boston, MA 02111 USA. [Brown, Catherine M.] Massachusetts Dept Publ Hlth, Hinton State Lab Inst, Jamaica Plain, MA USA. RP Weil, AA (reprint author), Massachusetts Gen Hosp, Dept Med, Wang Ambulatory Care Ctr 645, 15 Parkman St, Boston, MA 02114 USA. EM aweil@partners.org NR 23 TC 9 Z9 9 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAR PY 2012 VL 87 IS 3 BP 233 EP 239 DI 10.1016/j.mayocp.2011.09.008 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 910MO UT WOS:000301642000009 PM 22386178 ER PT J AU Shampo, MA Kyle, RA Steensma, DP AF Shampo, Marc A. Kyle, Robert A. Steensma, David P. TI Alexander Todd-British Nobel Laureate SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Shampo, Marc A.; Kyle, Robert A.] Mayo Clin, Rochester, MN 55905 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shampo, MA (reprint author), Mayo Clin, Rochester, MN 55905 USA. OI Steensma, David/0000-0001-5130-9284 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 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAR PY 2012 VL 87 IS 3 BP E19 EP E19 DI 10.1016/j.mayocp.2011.12.009 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 910MO UT WOS:000301642000002 PM 22386189 ER PT J AU Wood, KH Hoef, LWV Knight, DC AF Wood, Kimberly H. Hoef, Lawrence W. Ver Knight, David C. TI Neural mechanisms underlying the conditioned diminution of the unconditioned fear response SO NEUROIMAGE LA English DT Article DE fMRI; Learning; Conditioning; Unconditioned response; Amygdala; Prefrontal cortex; Emotion; Fear; Anxiety; Skin conductance ID HUMAN AMYGDALA ACTIVITY; TRAIT ANXIETY; WITHIN-SUBJECT; FUNCTIONAL MRI; EXTINCTION; ACTIVATION; EXPRESSION; FMRI; UNCERTAINTY; EMOTION AB Recognizing cues that predict an aversive event allows one to react more effectively under threatening conditions, and minimizes the reaction to the threat itself. This is demonstrated during Pavlovian fear conditioning when the unconditioned response (UCR) to a predictable unconditioned stimulus (UCS) is diminished compared to the UCR to an unpredictable UCS. The present study investigated the functional magnetic resonance imaging (fMRI) signal response associated with Pavlovian conditioned UCR diminution to better understand the relationship between individual differences in behavior and the neural mechanisms of the threat-related emotional response. Healthy volunteers participated in a fear conditioning study in which trait anxiety, skin conductance response (SCR), UCS expectancy, and the fMRI signal were assessed. During acquisition trials, a tone (CS +) was paired with a white noise UCS and a second tone (CS -) was presented without the UCS. Test trials consisted of the CS + paired with the UCS, CS - paired with the UCS, and presentations of the UCS alone to assess conditioned UCR diminution. UCR diminution was observed within the dorsolateral PFC, dorsomedial PFC, cingulate cortex, inferior parietal lobule (IPL), anterior insula, and amygdala. The threat-related activity within the dorsolateral PFC, dorsomedial PFC, posterior cingulate cortex, and IPL varied with individual differences in trait anxiety. In addition, anticipatory (i.e. CS elicited) activity within the PFC showed an inverse relationship with threat-related (i.e. UCS elicited) activity within the PFC. IPL, and amygdala. Further, the emotional response (indexed via SCR) elicited by the threat was closely linked to amygdala activity. These findings are consistent with the view that the amygdala and PFC support learning-related processes that influence the emotional response evoked by a threat. (C) 2011 Elsevier Inc. All rights reserved. C1 [Wood, Kimberly H.; Knight, David C.] Univ Alabama, Dept Psychol, Civitan Int Res Ctr, Birmingham, AL 35294 USA. [Hoef, Lawrence W. Ver] Univ Alabama, Dept Neurol, Sch Med, Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Knight, DC (reprint author), CIRC 235H,1530 3RD AVE S, Birmingham, AL 35294 USA. EM knightdc@uab.edu FU University of Alabama at Birmingham Faculty FX This research was supported by the University of Alabama at Birmingham Faculty Development Grant Program. NR 71 TC 19 Z9 19 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2012 VL 60 IS 1 BP 787 EP 799 DI 10.1016/j.neuroimage.2011.12.048 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 904SR UT WOS:000301218700079 PM 22227141 ER PT J AU Lee, JM Ramos, EM Lee, JH Gillis, T Mysore, JS Hayden, MR Warby, SC Morrison, P Nance, M Ross, CA Margolis, RL Squitieri, F Orobello, S Di Donato, S Gomez-Tortosa, E Ayuso, C Suchowersky, O Trent, RJA McCusker, E Novelletto, A Frontali, M Jones, R Ashizawa, T Frank, S Saint-Hilaire, MH Hersch, SM Rosas, HD Lucente, D Harrison, MB Zanko, A Abramson, RK Marder, K Sequeiros, J Paulsen, JS Landwehrmeyer, GB Myers, RH MacDonald, ME Gusella, JF AF Lee, J. -M. Ramos, E. M. Lee, J. -H. Gillis, T. Mysore, J. S. Hayden, M. R. Warby, S. C. Morrison, P. Nance, M. Ross, C. A. Margolis, R. L. Squitieri, F. Orobello, S. Di Donato, S. Gomez-Tortosa, E. Ayuso, C. Suchowersky, O. Trent, R. J. A. McCusker, E. Novelletto, A. Frontali, M. Jones, R. Ashizawa, T. Frank, S. Saint-Hilaire, M. H. Hersch, S. M. Rosas, H. D. Lucente, D. Harrison, M. B. Zanko, A. Abramson, R. K. Marder, K. Sequeiros, J. Paulsen, J. S. Landwehrmeyer, G. B. Myers, R. H. MacDonald, M. E. Gusella, J. F. CA PREDICT-HD Study Huntington REGISTRY Study European HD-MAPS Study Grp COHORT Study HSG TI CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion SO NEUROLOGY LA English DT Article ID TRINUCLEOTIDE REPEAT; OF-ONSET; LENGTH; HOMOZYGOSITY; CHROMOSOMES; MUTATION; ALLELE; GENE; HD AB Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e. g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology (R) 2012; 78: 690-695 C1 [Lee, J. -M.; Lee, J. -H.; Gillis, T.; Mysore, J. S.; Lucente, D.; MacDonald, M. E.; Gusella, J. F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ramos, E. M.] Univ Porto, UnIGENe, IBMC Inst Mol & Cellular Biol, P-4100 Oporto, Portugal. [Sequeiros, J.] Univ Porto, Inst Ciencias Biomed Abel Salazar, P-4100 Oporto, Portugal. [Hayden, M. R.; Warby, S. C.] Univ British Columbia, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 1M9, Canada. [Morrison, P.] Univ Ulster, Coleraine BT52 1SA, Londonderry, North Ireland. Belfast HSC Trust, Reg Med Genet Ctr, Belfast, Antrim, North Ireland. [Nance, M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Ross, C. A.; Margolis, R. L.] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Squitieri, F.; Orobello, S.] IRCCS Neuromed, Neurogenet Unit, Pozzilli, Italy. [Squitieri, F.; Orobello, S.] IRCCS Neuromed, Ctr Rare Dis, Pozzilli, Italy. [Di Donato, S.] Ist Nazl Neurol Carlo Besta, Milan, Italy. [Gomez-Tortosa, E.] Fdn Jimenez Diaz, Dept Neurol, E-28040 Madrid, Spain. [Ayuso, C.] Fdn Jimenez Diaz, Dept Genet, E-28040 Madrid, Spain. [Suchowersky, O.] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Trent, R. J. A.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [McCusker, E.] Westmead Hosp, Dept Neurol, Sydney, NSW, Australia. [Novelletto, A.] Univ Roma Tor Vergata, Dept Biol, I-00173 Rome, Italy. [Frontali, M.] Inst Neurobiol & Mol Med, Rome, Italy. [Jones, R.] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Atlanta, GA USA. [Ashizawa, T.] Univ Florida, Dept Neurol, Gainesville, FL USA. [Frank, S.; Saint-Hilaire, M. H.; Myers, R. H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Hersch, S. M.; Rosas, H. D.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. [Harrison, M. B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Zanko, A.] Univ Calif San Francisco, Memory & Aging Ctr, San Francisco, CA 94143 USA. [Abramson, R. K.] Univ S Carolina, Sch Med, Dept Neuropsychiat & Behav Sci, Columbia, SC 29208 USA. [Marder, K.] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA. [Paulsen, J. S.] Univ Iowa, Dept Psychiat, Roy & Lucille Carver Coll Med, Iowa City, IA 52242 USA. [Paulsen, J. S.] Univ Iowa, Dept Neurol, Roy & Lucille Carver Coll Med, Iowa City, IA 52242 USA. [Landwehrmeyer, G. B.] Univ Ulm, Dept Neurol, D-7900 Ulm, Germany. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM gusella@helix.mgh.harvard.edu RI Di Donato, Stefano/B-9717-2012; Ross, Christopher/H-8395-2013; Raymond, Lynn/A-6664-2010; Gago, Miguel/F-2355-2015; Almeida Garrett, Maria Carolina/A-5332-2012; Hayden, Michael/D-8581-2011; OI Rosser, Anne/0000-0002-4716-4753; Kloppel, Gunter/0000-0002-6688-086X; Elifani, Francesca/0000-0002-0824-9543; Raymond, Lynn/0000-0002-8610-1042; Gago, Miguel/0000-0003-0894-6207; Almeida Garrett, Maria Carolina/0000-0003-3336-3302; Hayden, Michael/0000-0001-5159-1419; Saint-Hilaire, Marie-Helene/0000-0002-2355-5979; Myers, Richard/0000-0002-8365-2674; Sequeiros, Jorge/0000-0002-9846-1037; BAS, JORDI/0000-0002-4478-421X; Calopa, Matilde/0000-0002-6943-3707; Mandich, Paola/0000-0003-3123-3512; Wild, Edward/0000-0002-6921-7887; Dunnett, Stephen/0000-0003-1826-1578; Novelletto, Andrea/0000-0002-1146-7680; Ayuso, Carmen/0000-0002-9242-7065; Squitieri, Ferdinando /0000-0002-7397-1727; Landwehrmeyer, Georg Bernhard/0000-0003-3375-790X FU National Institute of Neurological Disorders and Stroke (NINDS) [NS016367]; CHDI Foundation, Inc.; Huntington's Disease Society of America; National Research Foundation of Korea [NRF-2009-352E0010]; Fundacao para e a Tecnologia of Portugal (FCT) [SFRH/BD/44335/2008]; National Institutes of Health NINDS [NS016367, NS024279, NS032765, NS033648, NS040068, NS044466, NS036630, NS052592, NS060118, NS16375, NS055252., NS069422, NS016375, NS044431, NS068897, NS050095]; High Q Foundation; National Parkinson Foundation; Santhera Pharmaceuticals; Medivation/Pfizer; Neuro-Search; Schwarz Biosciences; IMPAX Pharmaceuticals; Neuraltus Pharmaceuticals; Teva Pharmaceuticals; National Institutes of Health NCCAM [AT000613]; NHGRI [HG02449]; Michael J. Fox Foundation/Northwestern Dixon Foundation; Forest Laboratory; Ministero della Salute, Italy; Fondazione Cariplo, Milan, Italy; CIBERER, ISCIII, Madrid, Spain; Abbott Laboratories; Australian Research Council LIED [LE0989147, LE100100130]; Italian Drug Agency (AIFA) [FARM659PTX]; Lundbeck Pharmaceuticals; Bayer; EMD Serono; Michael J. Fox Foundation; National Institutes of Health NICHD [HD062550, HD06528]; South Carolina Council [18120 FL00]; Fullerton Foundation; Amarin Corporation; NeuroSearch Sweden AB; Medivation; NCRR [RR024156, PO412196-G]; Parkinson Study Group; European Commission; European Union; High Q Foundation/CHDI Foundation; Jerry MacDonald Huntington Research Fund; NIGMS [GM061354]; Simons Foundation FX Supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS) ("Huntington's Disease Center Without Walls"; NS016367), the CHDI Foundation, Inc., and the Huntington's Disease Society of America's Coalition for the Cure. J.H.L. received a fellowship from the National Research Foundation of Korea and E.M.R. received a scholarship from the Fundacao para e a Tecnologia of Portugal (FCT). PREDICT-HD is supported by NINDS grant NS040068. Both PREDICT-HD and COHORT are also supported by the CHDI Foundation, Inc. and REGISTRY is supported by the High Q Foundation.; Dr. J-M. Lee reports no disclosures. Dr. Ramos received a scholarship from FCT (SFRH/BD/44335/2008). Dr. J.-H. Lee received support from the National Research Foundation of Korea (NRF-2009-352E0010). Dr. Gillis and Dr. Mysore report no disclosures. Dr. Hayden serves as Editor-in-Chief of Clinical Genetics. Dr. Warby reports no disclosures. Dr. Morrison is a section editor of The Oncologist. Dr. Nance received honoraria from the Huntington's Disease Society of America HD Training Course for Physicians, the American Academy of Neurology Genetics in Neurology lecture and lectures at Augsburg College, royalties from Oxford University Press for Juvenile Huntington's Disease 2009, reimbursement for NIH Study Section service and the Parkinson Study Group Scientific Review Board, Center of Excellence support from the Huntington Disease Society of America and the National Parkinson Foundation, and grant support from Santhera Pharmaceuticals, Neuro-Search, Medivation/Pfizer, Schwarz Biosciences, IMPAX Pharmaceuticals, Neuraltus Pharmaceuticals and Teva Pharmaceuticals, National Institutes of Health NINDS grants NS044466, NS036630, NS040068, NS052592, and NS060118, NCCAM grant AT000613 and NHGRI grant HG02449, and grants from the CHDI Foundation (HP Therapeutics), the High Q Foundation, and the Michael J. Fox Foundation/Northwestern Dixon Foundation, and declares spousal participation in Speaker's bureaus: Roche, Sanford. Dr. Ross received research funding from National Institutes of Health NINDS grants NS16375, NS055252, NS060118, and NS069422. Dr. Margolis received research funding from National Institutes of Health NINDS grant NS016375, Medivation/Pfizer, CHDI Foundation Inc., and Forest Laboratories and was a consultant to AstraZeneca. Dr. Squitieri and Dr. Orobello report no disclosures. Dr. Di Donato was on the Scientific Advisory Board of the Fondazione Mariani Onlus, Milan, Italy, and a consultant Advisor for Preclinical Research and International Relationships of the Scientific Direction of the Fondazione IRCSS Instituto Neurologico Carlo Besta, Milan, Italy, and received support from the Ministero della Salute, Italy, and from the Fondazione Cariplo, Milan, Italy. Dr. Gomez-Tortosa reports no disclosures. Dr. Ayuso has received research support from CIBERER, ISCIII, Madrid, Spain. Dr. Suchowersky was an Advisory Board Member for Allergan, Biovail and Novartis, on the editorial boards of the Canadian Journal of Neurological Sciences and Nature Reviews Neurology, and received support from Abbott Laboratories, from National Institutes of Health NINDS grant NS044431, and from the CHDI Foundation, Inc. Dr. Trent reports royalties for the book Molecular Medicine, 3rd edition (Elsevier) and support from Australian Research Council LIED grants LE0989147 and LE100100130. Dr. McCusker is on the editorial board of Tremor and Hyperkinetic Movements. Dr. Novelletto reports no disclosures. Dr. Frontali received support from Italian Drug Agency (AIFA) grant FARM659PTX. Dr. Jones received support from the National Institutes of Health NINDS grants NS040068 and NS060118 and from the High Q Foundation and the Huntington's Disease Society of America. Dr. Ashizawa received support from the National Institutes of Health NINDS grant NS068897. Dr. Frank consulted for and received support from Lundbeck Pharmaceuticals. Dr.; Saint-Hilaire was on the Steering Committee of the Safinamide (MOTION) study of EMD Serono, lectured at the meetings of the Movement Disorder Society and the American Academy of Neurology, is a member of the speaker's bureau of Teva Pharmacuticals, and received support from Bayer, EMD Serono, and Teva Pharmaceuticals, National Institutes of Health NINDS grant NS050095, and NHGRI grant HG02449, and from the Michael J. Fox Foundation. Dr. Hersch was a consultant to Link Medicine and Alnylam Pharmaceuticals and received support from the National Institutes of Health NCCAM grant AT000613, NINDS grant NS071789, and from the Huntington's Disease Society of America. Dr. Rosas and Dr. Lucente report no disclosures. Dr. Harrison received support from National Institutes of Health NCCAM grant AT000613, from the CHDI Foundation, Inc., and from the Huntington's Disease Society of America. Dr. Zanko reports no disclosures. Dr. Abramson received support from National Institutes of Health NICHD grant HD062550, South Carolina Council on Disabilities grant 18120 FL00, and a grant from the Fullerton Foundation. Dr. Marder served on the editorial board of Neurology (R) and as an editor of Current Neurology and Neuroscience and received support from Amarin Corporation, NeuroSearch Sweden AB, and Medivation, and from National Institutes of Health NINDS grant NS036630, NCRR grant RR024156, and PO412196-G from NHGRI grant HG02449 at the University of Rochester as well as from the Parkinson Disease Foundation, the Huntington's Disease Society of America, the Parkinson Study Group, the Michael J. Fox Foundation, and the CHDI Foundation, Inc. Dr. Sequeiros was a compensated speaker for the Fundacion Jimenez Diaz, served on the editorial boards of Clinical Genetics, the Journal of Community Genetics, and the Journal of Biomedicine and Biotechnology, and received research support from the FCT "Financiamento Plurianual de Unidades de investigacao" and from the European Commission FP6 Network of Excellence EuroGentest: Genetics Testing in Europe. Dr. Paulsen received funding from National Institutes of Health NINDS grant NS040068 and from the CHDI Foundation, Inc. Dr. Landwehrmeyer received a speaker honorarium/reimbursement from DGNP- Temmler Pharma, royalties from Neurologie Compact (Verlag) and Juvenile HD (Oxford Press), consulting support from the CHDI Foundation, Inc., clinical trial support from Medivation and Neurosearch, and support from the European Union (FP7 Paddington) and the High Q Foundation/CHDI Foundation. Dr. Myers received funding from National Institutes of Health NINDS grant NS016367 and from the Jerry MacDonald Huntington Research Fund. Dr. MacDonald serves as an Associate Editor of PLoS Genetics, is on the Board of Directors of the Huntington's Disease Society of America, and received support from National Institutes of Health NINDS grants NS016367, NS032765, and NS033648 and from the Huntington's Disease Society of America and the CHDI Foundation, Inc. Dr. Gusella is on the Scientific Advisory Board of Quest Diagnostics, Inc., is on the editorial boards of DNA and Cell Biology, Neurobiology of Disease, Neurogenetics, Biomed Central Neuroscience, Biomed Central Biology, and Molecular Autism, and received support from National Institutes of Health NINDS grants NS016367, NS024279, and NS069422, NIGMS grant GM061354, and NICHD grant HD06528 and from the Simons Foundation Autism Research Initiative, Autism Speaks, CHDI Foundation, Inc., and the Huntington's Disease Society of America. NR 22 TC 84 Z9 86 U1 2 U2 41 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR PY 2012 VL 78 IS 10 BP 690 EP 695 DI 10.1212/WNL.0b013e318249f683 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 904YR UT WOS:000301236400004 PM 22323755 ER PT J AU Bespalova, IN Angelo, GW Ritter, BP Hunter, J Reyes-Rabanillo, ML Siever, LJ Silverman, JM AF Bespalova, Irina N. Angelo, Gary W. Ritter, Ben P. Hunter, Jason Reyes-Rabanillo, Maria L. Siever, Larry J. Silverman, Jeremy M. TI Genetic Variations in the ADAMTS12 Gene are Associated with Schizophrenia in Puerto Rican Patients of Spanish Descent SO NEUROMOLECULAR MEDICINE LA English DT Article DE ADAMTS12; Association study; Schizophrenia; Case-control sample; Chromosome 5p13 ID THROMBOTIC THROMBOCYTOPENIC PURPURA; MATRIX METALLOPROTEINASES MMPS; ABDOMINAL AORTIC-ANEURYSM; SERIOUS MENTAL-ILLNESS; 409 EUROPEAN-ANCESTRY; LOW-BIRTH-WEIGHT; PATERNAL SCHIZOPHRENIA; POSITIONAL CANDIDATE; SUSCEPTIBILITY LOCI; TISSUE INHIBITORS AB ADAMTS12 belongs to the family of metalloproteinases that mediate a communication between specific cell types and play a key role in the regulation of normal tissue development, remodeling, and degradation. Members of this family have been implicated in neurodegenerative and neuroinflammatory, as well as in muscular-skeletal, cardiovascular, respiratory and renal diseases, and cancer. Several metalloproteinases have been associated with schizophrenia. In our previous study of the pedigree from a genetic isolate of Spanish origin in Puerto Rico, we identified a schizophrenia susceptibility locus on chromosome 5p13 containing ADAMTS12. This gene, therefore, is not only a functional but also a positional candidate gene for susceptibility to the disorder. In order to examine possible involvement of ADAMTS12 in schizophrenia, we performed mutation analysis of the coding, 5'- and 3'-untranslated, and putative promoter regions of the gene in affected members of the pedigree and identified 18 sequence variants segregated with schizophrenia. We then tested these variants in 135 unrelated Puerto Rican schizophrenia patients of Spanish origin and 203 controls and identified the intronic variant rs256792 (P = 0.0035; OR = 1.59; 95% CI = 1.16-2.17) and the two-SNP haplotype rs256603-rs256792 (P = 0.0023; OR = 1.62; 95% CI = 1.19-2.21) associated with the disorder. The association remained significant after correction for multiple testing. Our data support the hypothesis that genetic variations in ADAMTS12 influence the risk of schizophrenia. C1 [Bespalova, Irina N.; Angelo, Gary W.; Ritter, Ben P.; Hunter, Jason; Siever, Larry J.; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Bespalova, Irina N.; Angelo, Gary W.; Ritter, Ben P.; Siever, Larry J.; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Reyes-Rabanillo, Maria L.] San Juan Veteran Affairs Med Ctr, San Juan, PR USA. RP Bespalova, IN (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1 Gustave Levy Pl,Box 1230, New York, NY 10029 USA. EM irina.bespalova@mssm.edu FU National Alliance for Research on Schizophrenia and Depression (NARSAD); National Institute of Mental Health (NIMH) [MH082134]; Department of Veterans Affairs (VA) FX The authors thank patients and healthy volunteers for their participation in the study. We also thank Enrique Rossy-Fullana and Jose Carrion-Baralt for samples collection and administrative assistance. We thank Martina Durner and James Schmeidler for helpful discussions and Inga Peter for assistance with logistic regression analysis. We are grateful to Andrei Kurochkin and anonymous reviewers for critical reading of the manuscript and useful comments and suggestions. The study was supported by the National Alliance for Research on Schizophrenia and Depression (NARSAD) to INB (Young Investigator Award), the National Institute of Mental Health (NIMH) to INB (RO3 Award MH082134), and The Department of Veterans Affairs (VA) to JMS (Merit Award). The funding sources had no role in study design, analysis and interpretation of the data, and writing the manuscript. NR 101 TC 5 Z9 6 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PD MAR PY 2012 VL 14 IS 1 BP 53 EP 64 DI 10.1007/s12017-012-8169-y PG 12 WC Neurosciences SC Neurosciences & Neurology GA 909TY UT WOS:000301589200005 PM 22322903 ER PT J AU Deason, RG Hussey, EP Budson, AE Ally, BA AF Deason, Rebecca G. Hussey, Erin P. Budson, Andrew E. Ally, Brandon A. TI Gist-Based Conceptual Processing of Pictures Remains Intact in Patients With Amnestic Mild Cognitive Impairment SO NEUROPSYCHOLOGY LA English DT Article DE picture superiority effect; mild cognitive impairment; Alzheimer's disease; familiarity; recollection ID EVENT-RELATED POTENTIALS; ALZHEIMERS-DISEASE; FALSE RECOGNITION; PICTORIAL SUPERIORITY; CATEGORIZED PICTURES; MEMORY; FAMILIARITY; FLUENCY; DEMENTIA; RECOLLECTION AB Objective: The picture superiority effect, better memory for pictures compared to words, has been found in young adults, healthy older adults, and, most recently, in patients with Alzheimer's disease and mild cognitive impairment. Although the picture superiority effect is widely found, there is still debate over what drives this effect. One main question is whether it is enhanced perceptual or conceptual information that leads to the advantage for pictures over words. In this experiment, we examined the picture superiority effect in healthy older adults and patients with amnestic mild cognitive impairment (MCI) to better understand the role of gist-based conceptual processing. Method: We had participants study three exemplars of categories as either words or pictures. In the test phase, participants were again shown pictures or words and were asked to determine whether the item was in the same category as something they had studied earlier or whether it was from a new category. Results: We found that all participants demonstrated a robust picture superiority effect, better performance for pictures than for words. Conclusions: These results suggest that the gist-based conceptual processing of pictures is preserved in patients with MCI. While in healthy older adults preserved recollection for pictures could lead to the picture superiority effect, in patients with MCI it is most likely that the picture superiority effect is a result of spared conceptually based familiarity for pictures, perhaps combined with their intact ability to extract and use gist information. C1 [Deason, Rebecca G.; Budson, Andrew E.] VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, Boston, MA USA. [Deason, Rebecca G.; Budson, Andrew E.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02215 USA. [Hussey, Erin P.; Ally, Brandon A.] Vanderbilt Univ, Dept Neurol, Nashville, TN USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Psychol, Nashville, TN USA. [Ally, Brandon A.] Vanderbilt Univ, Dept Psychiat, Nashville, TN USA. RP Ally, BA (reprint author), A-0118 Med Ctr N,1161 21st Ave S, Nashville, TN 37232 USA. EM brandon.ally@vanderbilt.edu OI Ally, Brandon/0000-0002-6034-7968 FU National Institute on Aging [R01 AG038471, K23 AG031925, R01 AG025815, P30 AG13846]; Department of Veterans Affairs, Veterans Health Administration FX This research was supported by National Institute on Aging Grants R01 AG038471 (BAA), K23 AG031925 (BAA), R01 AG025815 (AEB), P30 AG13846 (AEB), and a Department of Veterans Affairs, Veterans Health Administration, VISN 1 Early Career Development Award to RGD. We thank Sean Flannery, Bruno Frustace, and Erin Reynolds for assistance with data collection. This material is also the result of work supported with resources and the use of facilities at the Bedford VA Hospital in Bedford, MA and the VA Boston Healthcare System, Boston, MA. NR 45 TC 8 Z9 8 U1 1 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAR PY 2012 VL 26 IS 2 BP 202 EP 208 DI 10.1037/a0026958 PG 7 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 906FP UT WOS:000301330600008 PM 22229341 ER PT J AU Rosenzweig, M Giblin, J Morse, A Sheehy, P Sommer, V AF Rosenzweig, Margaret Giblin, Joan Morse, Allison Sheehy, Patricia Sommer, Valerie CA Bridging Gap Working Grp TI Bridging the Gap: A Descriptive Study of Knowledge and Skill Needs in the First Year of Oncology Nurse Practitioner Practice SO ONCOLOGY NURSING FORUM LA English DT Article ID CARE; OUTCOMES AB Purpose/Objectives: To identify the knowledge and skill needs of oncology nurse practitioners (ONPs) as they enter cancer care practice, and to identify necessary educational resources. Design: Cross-sectional, descriptive. Setting: A national e-mail survey. Sample: 610 self-described ONPs from the Oncology Nursing Society's database. Methods: The project team developed a 28-item electronic survey. The survey was randomly distributed via e-mail. Main Research Variables: ONPs' feelings of preparedness in the first year of ONP practice. Findings: In the first year of practice, 90% of ONPs rated themselves as prepared or very prepared in obtaining patient history, performing physical examination, and documenting findings. ONPs rated themselves as not at all or somewhat prepared in clinical issues of chemotherapy/ biotherapy competency (n = 81, 78%), recognizing and managing oncologic emergencies, (n = 77, 70%), and recognizing and managing drug toxicities (n = 63, 61%). The primary source of oncology education for ONPs new to practice was almost exclusively the collaborating or supervising physician (n = 84, 81%). Conclusions: Specific knowledge and skills, such as information about chemotherapy, oncologic emergencies, and side effects of therapy, are needed before an ONP enters a cancer care practice. Implications for Nursing: Cancer-specific education should be made available to new ONPs as they begin independent practice. C1 [Rosenzweig, Margaret] Univ Pittsburgh Pennsylvania, Sch Nursing, Pittsburgh, PA 15260 USA. [Giblin, Joan] Emory Winship Canc Inst, Atlanta, GA USA. [Morse, Allison] Caritas St Elizabeths Med Ctr, Boston, MA USA. [Sheehy, Patricia] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sommer, Valerie] Kansas City Canc Ctr, US Oncol Network, Kansas City, MO USA. RP Rosenzweig, M (reprint author), Univ Pittsburgh Pennsylvania, Sch Nursing, Pittsburgh, PA 15260 USA. EM mros@pitt.edu NR 25 TC 4 Z9 4 U1 0 U2 3 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2012 VL 39 IS 2 BP 195 EP 201 DI 10.1188/12.ONF.195-201 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA 902KD UT WOS:000301036100013 PM 22374493 ER PT J AU Golier, JA Caramanica, K Yehuda, R AF Golier, Julia A. Caramanica, Kimberly Yehuda, Rachel TI Neuroendocrine response to CRF stimulation in veterans with and without PTSD in consideration of war zone era SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Medically unexplained illness; Gulf War syndrome; Stress; ACTH; Cortisol; CRF ID POSTTRAUMATIC-STRESS-DISORDER; CORTICOTROPIN-RELEASING HORMONE; SELF-REPORTED SYMPTOMS; GULF-WAR; INCREASED PITUITARY; COMBAT VETERANS; CORTISOL; ENDOCRINE; TRAUMA; BRAIN AB Background: Alterations in hypothalamic-pituitary-adrenal (HPA) axis activity have been observed in Gulf War veterans with posttraumatic stress disorder (PTSD) which differ from those observed in other veteran groups, raising the possibility that there is a unique neuroendocrine profile in this group of veterans. This study seeks to further characterize the effects of PTSD, military cohort (Vietnam, 1991 Gulf War, Operations Enduring Freedom/Iraqi Freedom (OEF/OIF)), and their interaction on the neuroendocrine response to synthetic corticotrophin-releasing factor (CRF) stimulation. Methods: 51 male veterans were studied consisting of 21 from the Vietnam era, 16 from the Gulf War era, and 14 from the OEF/OIF era. 16 of these veterans were deployed to a war zone and had chronic PTSD (PTSD+), 25 were deployed to a war zone and did not have chronic PTSD (PTSD), and 10 were not deployed to a war zone and did not have PTSD (non-exposed). The participants underwent the CRF stimulation test in the afternoon (approximately 2:00 p.m.), which measures the integrity and sensitivity of the pituitary adrenal axis. Plasma cortisol and adrenocorticotropic hormone (ACTH) were measured at baseline and at intervals over a 2 h period following intravenous administration of 1 mu g/kg of ovine CRF (o-CRF, max 100 mu g). In a small subset of participants, dehydroepiandrosterone (DHEA) and cortisol binding globulin (CBG) were also assessed. Results: There was a significant group by era interaction in the response of ACTH to CRF, in addition to a main effect of group (PTSD+, PTSD, non-exposed). The interaction reflected that group differences were only evident in the Gulf War cohort; among Gulf War era veterans, the PTSD+ group had higher elevations in ACTH levels following CRF than the PTSD group and the non-exposed group. Additionally, the peak change in ACTH was associated with a self-reported environmental exposure (pyridostigmine bromide ingestion) which has been found to be linked to the excess morbidity found in Gulf War veterans. Self-reported childhood trauma was greater in veterans of the Gulf War than Vietnam or OEF/OIF, but did not account for the observed differences. There was a significant effect of group on the cortisol response to CRF, reflecting greater responsivity in both of the deployed groups (PTSD+ and PTSD-) compared to the non-exposed group which could be accounted for by baseline differences in cortisol levels; unlike the ACTH response, the cortisol response did not differ by era. There were no effects of group, era, or their interaction on the DHEA and CBG response to CRF. Conclusions: A uniform pattern of PTSD-related alterations in the response to intravenous CRF was not found. Rather, PTSD-related alterations were found only in veterans of the 1991 Gulf War, and were characterized by an enhanced pituitary response to CRF which may reflect increased sensitivity of pituitary corticotrophs or CRF hyposecretion. Together with previous neuroendocrine findings, the data suggest the HPA axis is dysregulated in Gulf War veterans in unique ways which may reflect the long-term effects of environmental exposures in addition to disease effects. Further work is needed to characterize these effects and their impact on long-term psychological and medical outcomes. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Golier, Julia A.; Caramanica, Kimberly; Yehuda, Rachel] James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. [Golier, Julia A.; Yehuda, Rachel] Mt Sinai Sch Med, New York, NY USA. RP Golier, JA (reprint author), James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY USA. EM Julia.Golier@va.gov RI Schueter, nicos/A-3625-2014 FU VA MERIT; NIH [5 M01 RR00071] FX Funding for this study was provided by a VA MERIT award to Dr. Golier and by a grant (5 M01 RR00071) for the Mount Sinai General Clinical Research Center from the NIH; the VA and NIH had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 27 TC 6 Z9 6 U1 3 U2 8 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 MAR PY 2012 VL 37 IS 3 BP 350 EP 357 DI 10.1016/j.psyneuen.2011.07.004 PG 8 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 904QB UT WOS:000301211900005 PM 21813244 ER PT J AU Singh, AK Shankar, S Gervais, DA Hahn, PF Mueller, PR AF Singh, Ajay K. Shankar, Sridhar Gervais, Debra A. Hahn, Peter F. Mueller, Peter R. TI Image-guided Percutaneous Splenic Interventions SO RADIOGRAPHICS LA English DT Article ID NEEDLE-ASPIRATION BIOPSY; RADIOFREQUENCY ABLATION; THROMBIN INJECTION; CORE BIOPSY; CHRONIC-PANCREATITIS; ORIGINAL REPORT; SPLEEN; LIVER; PSEUDOANEURYSM; HYPERSPLENISM AB In the spleen, image-guided interventional procedures such as biopsy and catheter drainage have not been widely performed because of the perceived increased risk of complications. The ability of image-guided biopsy to allow tissue diagnosis of a focal splenic mass without the need for splenectomy is the driving force behind use of this procedure in oncology patients. The literature on image-guided splenic biopsy suggests that the highest biopsy yield is achieved with core biopsy and the lowest complication rate is achieved with fine-needle aspiration. Image-guided catheter drainage is an effective alternative to splenectomy for management of infected splenic collections. In clinical practice, image-guided splenic biopsy, fluid aspiration, and catheter drainage have high success rates. Image-guided alcohol ablation is effective in treatment of splenic cysts. The literature on splenic radiofrequency ablation (RFA) is sparse; therefore, further studies are needed to determine the role of RFA in management of splenic neoplasms and hypersplenism. Image-guided percutaneous thrombin injection can be used to treat splenic artery pseudoaneurysms. Awareness of the correct interventional techniques and their limitations is important for safe performance of image-guided percutaneous splenic interventions. C1 [Singh, Ajay K.; Gervais, Debra A.; Hahn, Peter F.; Mueller, Peter R.] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, Boston, MA 02114 USA. [Shankar, Sridhar] UT Med Grp, Dept Radiol, Memphis, TN USA. RP Singh, AK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. EM mghpartners@yahoo.com NR 31 TC 20 Z9 20 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2012 VL 32 IS 2 BP 523 EP 534 DI 10.1148/rg.322115135 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 908OT UT WOS:000301500400015 PM 22411947 ER PT J AU Elmer, J Alam, HB Wilcox, SR AF Elmer, Jonathan Alam, Hasan B. Wilcox, Susan R. TI Hemoglobin-based oxygen carriers for hemorrhagic shock SO RESUSCITATION LA English DT Review DE Hemorrhagic shock; Hemoglobin-based oxygen carriers; Blood alternatives; Transfusion ID CROSS-LINKED HEMOGLOBIN; HUMAN POLYMERIZED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; ACUTE LUNG INJURY; PRIMARY HIP-ARTHROPLASTY; RED-BLOOD-CELLS; NITRIC-OXIDE; DOUBLE-BLIND; ACUTE TRAUMA; PERIOPERATIVE HYPOTENSION AB Hemorrhagic shock is a pathologic state in which intravascular volume and tissue oxygen delivery are impaired, leading to circulatory collapse and cellular ischemia. Resuscitation with hemoglobin-based oxygen carriers (HBOCs) is appealing in that their use can both restore intravascular volume and tissue oxygenation, without the limitations in supply and immunomodulatory effects of packed red blood cells. However, the development of safe and effective agents has been elusive. In this article, we briefly discuss the major limitations of traditional resuscitative fluids which have driven the continued interest in HBOCs. We then review the history of early HBOC development and the modern understanding of their mechanisms of toxicity, which has informed the rational design of second-generation agents. Finally, we provide an overview of these second-generation HBOCs that are under active investigation or have recently completed phase 3 clinical trials. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Elmer, Jonathan] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Elmer, Jonathan] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Alam, Hasan B.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Elmer, J (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM jelmer@partners.org OI Wilcox, Susan/0000-0001-7477-7531 NR 87 TC 14 Z9 17 U1 3 U2 24 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD MAR PY 2012 VL 83 IS 3 BP 285 EP 292 DI 10.1016/j.resuscitation.2011.09.020 PG 8 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 910NF UT WOS:000301645700021 PM 21978876 ER PT J AU Handa, T Anada, T Honda, Y Yamazaki, H Kobayashi, K Kanda, N Kamakura, S Echigo, S Suzuki, O AF Handa, T. Anada, T. Honda, Y. Yamazaki, H. Kobayashi, K. Kanda, N. Kamakura, S. Echigo, S. Suzuki, O. TI The effect of an octacalcium phosphate co-precipitated gelatin composite on the repair of critical-sized rat calvarial defects SO ACTA BIOMATERIALIA LA English DT Article DE Octacalcium phosphate; Gelatin; Crystal growth; Bone regeneration; Biodegradation ID BETA-TRICALCIUM PHOSPHATE; MARROW STROMAL CELLS; MESENCHYMAL STEM-CELLS; CALCIUM-PHOSPHATE; BONE-MARROW; THERMODYNAMIC ANALYSIS; CRYSTAL MORPHOLOGY; GENE-EXPRESSION; MODEL SYSTEM; HYDROXYAPATITE AB This study was designed to investigate the extent to which an octacalcium phosphate/gelatin (OCP/Gel) composite can repair rat calvarial critical-sized defects (CSD). OCP crystals were grown with various concentrations of gelatin molecules and the OCP/Gel composites were characterized by chemical analysis. X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (TEM), selected area electron diffraction (SAED) and mercury intrusion porosimetry. The OCP/Gel composite disks received vacuum dehydrothermal treatment, were implanted in Wistar rat calvarial CSD for 4, 8 and 16 weeks, and then subjected to radiologic, histologic, histomorphometric and histochemical assessment. The attachment of mouse bone marrow stromal ST-2 cells on the disks of the OCP/Gel composites was also examined after 1 day of incubation. OCP/Gel composites containing 24 wt.%, 31 wt.% and 40 wt.% of OCP and with approximate pore sizes of 10-500 mu m were obtained. Plate-like crystals were observed closely associated with the Gel matrices. TEM. XRD, FTIR and SAED confirmed that the plate-like crystals were identical to those of the OCP phase, but contained a small amount of sphere-like amorphous material adjacent to the OCP crystals. The OCP (40 wt.%)/Gel composite repaired 71% of the CSD in conjunction with material degradation by osteoclastic cells, which reduced the percentage of the remaining implant to less than 3% within 16 weeks. Of the seeded ST-2 cells, 60-70% were able to migrate and attach to the OCP/Gel composites after 1 day of incubation, regardless of the OCP content. These results indicate that an OCP/Gel composite can repair rat calvarial CSD very efficiently and has favorable biodegradation characteristics. Therefore, it is hypothesized that host osteoblastic cells can easily migrate into an OCP/Gel composite. (c) 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Suzuki, O.] Tohoku Univ, Grad Sch Dent, Div Craniofacial Funct Engn, Aoba Ku, Sendai, Miyagi 9808575, Japan. [Handa, T.; Kobayashi, K.; Kanda, N.; Echigo, S.] Tohoku Univ, Grad Sch Dent, Div Oral Surg, Sendai, Miyagi 9808575, Japan. [Yamazaki, H.] Forsyth Inst, Dept Biomineralizat, Cambridge, MA USA. [Kamakura, S.] Tohoku Univ, Grad Sch Biomed Engn, Bone Regenerat Engn Lab, Sendai, Miyagi 9808575, Japan. RP Suzuki, O (reprint author), Tohoku Univ, Grad Sch Dent, Div Craniofacial Funct Engn, Aoba Ku, 4-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan. EM suzuki-o@m.tohoku.ac.jp RI Kamakura, Shinji/A-5385-2013 FU Ministry of Education, Science, Sports, and Culture of Japan [17076001, 19390490, 23390450, 23659909, 23106010]; Suzuken Memorial Foundation FX This study was supported in part by grants in aid (17076001, 19390490, 23390450, 23659909 and 23106010) from the Ministry of Education, Science, Sports, and Culture of Japan and the Suzuken Memorial Foundation. NR 74 TC 16 Z9 16 U1 6 U2 30 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 J9 ACTA BIOMATER JI Acta Biomater. PD MAR PY 2012 VL 8 IS 3 BP 1190 EP 1200 DI 10.1016/j.actbio.2011.12.002 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 902ZY UT WOS:000301083900025 PM 22198138 ER PT J AU Chen, LL Wu, JC Wang, LH Wang, J Qin, ZH Difiglia, M Lin, F AF Chen, Lei-lei Wu, Jun-chao Wang, Lin-hui Wang, Jin Qin, Zheng-hong Difiglia, Marian Lin, Fang TI Rapamycin prevents the mutant huntingtin-suppressed GLT-1 expression in cultured astrocytes SO ACTA PHARMACOLOGICA SINICA LA English DT Article DE Huntington's disease; huntingtin-552; GLT-1; glutamate uptake; autophagy; rapamycin; 3-MA ID UBIQUITIN-PROTEASOME SYSTEM; AGGREGATE-PRONE PROTEINS; CELL-CELL INTERACTIONS; GLUTAMATE TRANSPORTERS; NEUROLOGICAL SYMPTOMS; ALZHEIMERS-DISEASE; STRIATAL NEURONS; ALPHA-SYNUCLEIN; MOUSE MODEL; AUTOPHAGY AB Aim: To investigate the effects of rapamycin on glutamate uptake in cultured rat astrocytes expressing N-terminal 552 residues of mutant huntingtin (Htt-552). Methods: Primary astrocyte cultures were prepared from the cortex of postnatal rat pups. An astrocytes model of Huntington's disease was established using the astrocytes infected with adenovirus carrying coden gene of N-terminal 552 residues of Huntingtin. The protein levels of glutamate transporters GLT-1 and GLAST, the autophagic marker microtubule-associated protein 1A/1B-light chain 3 (LC3) and the autophagy substrate p62 in the astrocytes were examined using Western blotting. The mRNA expression levels of GLT-1 and GLAST in the astrocytes were determined using Real-time PCR. [H-3] glutamate uptake by the astrocytes was measured with liquid scintillation counting. Results: The expression of mutant Htt-552 in the astrocytes significantly decreased both the mRNA and protein levels of GLT-1 but not those of GLAST. Furthermore, Htt-552 significantly reduced [H-3] glutamate uptake by the astrocytes. Treatment with the autophagy inhibitor 3-MA (10 mmol/L) significantly increased the accumulation of mutant Htt-552, and reduced the expression of GLT-1 and [H-3] glutamate uptake in the astrocytes. Treatment with the autophagy stimulator rapamycin (0.2 mg/mL) significantly reduced the accumulation of mutant Htt-552, and reversed the changes in GLT-1 expression and [3H] glutamate uptake in the astrocytes. Conclusion: Rapamcin, an autophagy stimulator, can prevent the suppression of GLT-1 expression and glutamate uptake by mutant Htt-552 in cultured astrocytes. C1 [Chen, Lei-lei; Wu, Jun-chao; Wang, Lin-hui; Wang, Jin; Qin, Zheng-hong; Lin, Fang] Soochow Univ, Sch Pharmaceut Sci, Lab Aging & Nervous Dis, Suzhou 215123, Peoples R China. [Chen, Lei-lei; Wu, Jun-chao; Wang, Lin-hui; Wang, Jin; Qin, Zheng-hong; Lin, Fang] Soochow Univ, Sch Pharmaceut Sci, Dept Pharmacol, Suzhou 215123, Peoples R China. [Difiglia, Marian] Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA. [Difiglia, Marian] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Lin, F (reprint author), Soochow Univ, Sch Pharmaceut Sci, Lab Aging & Nervous Dis, Suzhou 215123, Peoples R China. EM bluestonelin@hotmail.com FU National Natural Science Foundation of China [30600197] FX We thank Prof Hai-yan LIU at Soochow University for providing help in the measurement of [3H]-glutamate. This work is supported by grants from the National Natural Science Foundation of China (No 30600197). NR 37 TC 8 Z9 8 U1 1 U2 4 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD MAR PY 2012 VL 33 IS 3 BP 385 EP 392 DI 10.1038/aps.2011.162 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 904IE UT WOS:000301187300011 PM 22266730 ER PT J AU Gonzalez, A Zvolensky, MJ Parent, J Grover, KW Hickey, M AF Gonzalez, Adam Zvolensky, Michael J. Parent, Justin Grover, Kristin W. Hickey, Michael TI HIV Symptom Distress and Anxiety Sensitivity in Relation to Panic, Social Anxiety, and Depression Symptoms Among HIV-Positive Adults SO AIDS PATIENT CARE AND STDS LA English DT Article ID QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; MEDICATION ADHERENCE; DRUG-USE; HIV/AIDS; IMPACT; WOMEN; VALIDATION AB Although past work has documented relations between HIV/AIDS and negative affective symptoms and disorders, empirical work has only just begun to address explanatory processes that may underlie these associations. The current investigation sought to test the main and interactive effects of HIV symptom distress and anxiety sensitivity in relation to symptoms of panic disorder (PD), social anxiety disorder (SA), and depression among people with HIV/AIDS. Participants were 164 adults with HIV/AIDS (17.1% women; mean age, 48.40) recruited from AIDS service organizations (ASOs) in Vermont/New Hampshire and New York City. The sample identified as 40.9% white/Caucasian, 31.1% black, 22.0% Hispanic, and 6.1% mixed/other; with more than half (56.7%) reporting an annual income less than or equal to $10,000. Both men and women reported unprotected sex with men as the primary route of HIV transmission (64.4% and 50%, respectively). HIV symptom distress and anxiety sensitivity (AS) were significantly positively related to PD, SA, and depression symptoms. As predicted, there was a significant interaction between HIV symptom distress and anxiety sensitivity in terms of PD and SA symptoms, but not depressive symptoms. Results suggest that anxiety sensitivity and HIV symptom distress are clinically relevant factors to consider in terms of anxiety and depression among people living with HIV/AIDS. It may be important to evaluate these factors among patients with HIV/AIDS to identify individuals who may be at a particularly high risk for anxiety and depression problems. Limitations included recruitment from ASOs, cross-sectional self-report data, and lack of a clinical diagnostic assessment. C1 [Gonzalez, Adam; Zvolensky, Michael J.; Parent, Justin; Grover, Kristin W.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Gonzalez, Adam] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Gonzalez, Adam] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Zvolensky, Michael J.] Univ Houston, Dept Psychol, Houston, TX USA. [Hickey, Michael] Village Care, Adult Day Treatment Program, New York, NY USA. RP Gonzalez, A (reprint author), 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM agonzalez14@partners.org RI Ghartouchent, malek/B-9088-2012 FU McNeil Prevention and Community; University of Vermont FX This project was funded by a McNeil Prevention and Community Psychology grant awarded to Dr. Gonzalez and a University of Vermont Undergraduate Research Endeavors Competitive Award granted to Mr. Parent. NR 55 TC 18 Z9 18 U1 4 U2 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD MAR PY 2012 VL 26 IS 3 BP 156 EP 164 DI 10.1089/apc.2011.0309 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 901CI UT WOS:000300938900005 PM 22248334 ER PT J AU Rodriguez, F Peralta, CA Green, AR Lopez, L AF Rodriguez, Fatima Peralta, Carmen A. Green, Alexander R. Lopez, Lenny TI Comparison of C-Reactive Protein Levels in Less Versus More Acculturated Hispanic Adults in the United States (from the National Health and Nutrition Examination Survey 1999-2008) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; RISK-FACTOR; CARDIOVASCULAR-DISEASE; LIFE-STYLE; LATINOS; ATHEROSCLEROSIS; PREDICTORS; WOMEN AB Greater acculturation has been linked to increased risk of cardiovascular disease in Hispanics. C-reactive protein (CRP), a marker of inflammation, is known to be associated with an increased risk of cardiovascular disease morbidity and mortality. Whether acculturation is associated with CRP levels in Hispanics has not been established. We examined the association between acculturation and CRP in 11,858 Hispanic-American adults participating in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008. Acculturation was measured by the Short Acculturation Scale (SAS), a validated language-based scale. We used multivariate linear regression to examine the independent association between acculturation and CRP after adjusting for clinical and demographic covariates and appropriate sampling weights. We back-transformed the beta coefficients into relative differences (RDs). Higher acculturation was independently associated with higher CRP levels in Hispanics. Compared to those less acculturated, the RD in CRP levels was 52% higher (p = 0.003) for more acculturated Hispanics. Other significant predictors of CRP in Hispanics included a higher body mass index (RD 139% higher per 5 kg/m(2)), female gender (RD 36% higher), education level (RD 19% higher levels for at least a high school education, p <0.001), being insured (RD 27% higher CRP level, p = 0.006), having hypertension (RD 40% higher CRP levels, p <0.001), and statin use (RD 22% lower CRP levels, p = 0.002). In conclusion, higher acculturation was associated with increased CRP levels in Hispanics in a nationally representative population survey. Inflammation may play an important role in explaining the association between acculturation and increased cardiovascular risk. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:665-669) C1 [Rodriguez, Fatima] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Lopez, Lenny] Brigham & Womens Hosp, Brigham & Womens Acad Hospitalist Program, Boston, MA USA. [Peralta, Carmen A.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA USA. [Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Rodriguez, Fatima; Green, Alexander R.; Lopez, Lenny] Harvard Univ, Sch Med, Boston, MA USA. [Green, Alexander R.; Lopez, Lenny] Mongan Inst Hlth Policy, Boston, MA USA. [Green, Alexander R.; Lopez, Lenny] Massachusetts Gen Hosp, Dis Solut Ctr, Boston, MA USA. RP Rodriguez, F (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM farodriguez@partners.org NR 29 TC 4 Z9 4 U1 2 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2012 VL 109 IS 5 BP 665 EP 669 DI 10.1016/j.amjcard.2011.10.020 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 907CA UT WOS:000301394200011 PM 22169128 ER PT J AU Cannizzo, E Carulli, G Del Vecchio, L Ottaviano, V Bellio, E Zenari, E Azzara, A Petrini, M Preffer, F AF Cannizzo, Elisa Carulli, Giovanni Del Vecchio, Luigi Ottaviano, Virginia Bellio, Emanuele Zenari, Ezio Azzara, Antonio Petrini, Mario Preffer, Frederic TI The Role of CD19 and CD27 in the Diagnosis of Multiple Myeloma by Flow Cytometry A New Statistical Model SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Multiple myeloma; Flow cytometry; CD19 and CD27 expression ID MINIMAL RESIDUAL DISEASE; MALIGNANT PLASMA-CELLS; HIGH-DOSE THERAPY; MONOCLONAL GAMMOPATHY; BONE-MARROW; UNDETERMINED SIGNIFICANCE; ANTIGENIC EXPRESSION; IDENTIFICATION; DISORDERS; DIFFERENTIATION AB We have developed a new statistical diagnostic model that examines the correlation between immunophenotype and clonality as detected by flow cytometry (FC) and histology, defining the diagnostic role of FC in multiple myeloma (MM). The 192 bone marrow samples from patients and control subjects were studied for routine diagnostic analysis of MM; a minimum of 100 plasma cells (PCs) were analyzed for each patient sample. A direct 7- or 8-color method was applied to study the immunophenotype of PCs, utilizing a FACSCanto II (BD Biosciences, San Jose, CA). Samples were labeled with fluorochrome-conjugated monoclonal antibodies (AmCyan, Pac Blue, fluorescein isothiocyanate, phycoerythrin [PE], PECy7, peridinin-chlorophyll protein, allophycocyanin [APC], and APC-Cy7) to the following antigens: CD138, CD81, CD200, CD221, CD45, CD38, CD28, CD19, CD27, CD117, CD38, CD33, C'D20, CD56, CD10, and immunoglobulin K and A light chains. Among all antigens tested, CD19 and CD27, when applied to our model, resulted in optimal concordance with histology. This model defines the effective diagnostic role FC could have in MM and in the detection of minimal residual disease. C1 [Cannizzo, Elisa; Carulli, Giovanni; Ottaviano, Virginia; Bellio, Emanuele; Zenari, Ezio; Azzara, Antonio; Petrini, Mario] Univ Pisa, Sect Hematol, Dept Oncol Transplants & Adv Med, Pisa, Italy. [Del Vecchio, Luigi] Univ Naples Federico 2, Dept Biochem & Med Biotechnol, CEINGE Inst, Naples, Italy. [Preffer, Frederic] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Preffer, Frederic] Harvard Univ, Sch Med, Boston, MA USA. RP Cannizzo, E (reprint author), Santa Chiara Hosp, Div Hematol, Via Roma 67, I-56126 Pisa, Italy. NR 49 TC 13 Z9 14 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAR PY 2012 VL 137 IS 3 BP 377 EP 386 DI 10.1309/AJCP63TOCFNAMDMS PG 10 WC Pathology SC Pathology GA 902YV UT WOS:000301081000006 PM 22338049 ER PT J AU Cole, SR Hudgens, MG Tien, PC Anastos, K Kingsley, L Chmiel, JS Jacobson, LP AF Cole, Stephen R. Hudgens, Michael G. Tien, Phyllis C. Anastos, Kathryn Kingsley, Lawrence Chmiel, Joan S. Jacobson, Lisa P. TI Marginal Structural Models for Case-Cohort Study Designs to Estimate the Association of Antiretroviral Therapy Initiation With Incident AIDS or Death SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE acquired immunodeficiency syndrome; case-cohort studies; cohort studies; confounding bias; HIV; pharmacoepidemiology; selection bias ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROPENSITY SCORES; SURVIVAL ANALYSIS; CAUSAL INFERENCE; VIRAL LOAD; DISEASE; HIV; INTERVENTIONS; REGRESSION; MORTALITY AB To estimate the association of antiretroviral therapy initiation with incident acquired immunodeficiency syndrome (AIDS) or death while accounting for time-varying confounding in a cost-efficient manner, the authors combined a case-cohort study design with inverse probability-weighted estimation of a marginal structural Cox proportional hazards model. A total of 950 adults who were positive for human immunodeficiency virus type 1 were followed in 2 US cohort studies between 1995 and 2007. In the full cohort, 211 AIDS cases or deaths occurred during 4,456 person-years. In an illustrative 20% random subcohort of 190 participants, 41 AIDS cases or deaths occurred during 861 person-years. Accounting for measured confounders and determinants of dropout by inverse probability weighting, the full cohort hazard ratio was 0.41 (95% confidence interval: 0.26, 0.65) and the case-cohort hazard ratio was 0.47 (95% confidence interval: 0.26, 0.83). Standard multivariable-adjusted hazard ratios were closer to the null, regardless of study design. The precision lost with the case-cohort design was modest given the cost savings. Results from Monte Carlo simulations demonstrated that the proposed approach yields approximately unbiased estimates of the hazard ratio with appropriate confidence interval coverage. Marginal structural model analysis of case-cohort study designs provides a cost-efficient design coupled with an accurate analytic method for research settings in which there is time-varying confounding. C1 [Cole, Stephen R.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Hudgens, Michael G.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA. [Tien, Phyllis C.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Anastos, Kathryn] Montefiore Med Ctr, Bronx, NY 10467 USA. [Anastos, Kathryn] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Kingsley, Lawrence] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. [Chmiel, Joan S.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Jacobson, Lisa P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Cole, SR (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, MacGavran Greenberg Hall,CB 7435, Chapel Hill, NC 27599 USA. EM cole@unc.edu FU National Institutes of Health [R01-AA-017594, R01-AI-085073]; National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Cancer Institute [UO1-AI-35042, UL1-RR025005, UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131] FX Dr. Stephen Cole was partially supported by National Institutes of Health grant R01-AA-017594. Dr. Michael Hudgens was partially supported by National Institutes of Health grant R01-AI-085073. The Multicenter AIDS Cohort Study is funded by the National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute (grants UO1-AI-35042, UL1-RR025005 (General Clinical Research Center), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, and UO1-AI-35041). The Women's Interagency HIV Study is funded by the National Institute of Allergy and Infectious Diseases (grants UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (grant UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI grant UL1 RR024131). NR 43 TC 5 Z9 5 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 2012 VL 175 IS 5 BP 381 EP 390 DI 10.1093/aje/kwr346 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 898GT UT WOS:000300728800005 PM 22302074 ER PT J AU Sinkowitz-Cochran, RL Burkitt, KH Cuerdon, T Harrison, C Gao, SS Obrosky, DS Jain, R Fine, MJ Jernigan, JA AF Sinkowitz-Cochran, Ronda L. Burkitt, Kelly H. Cuerdon, Timothy Harrison, Cassandra Gao, Shasha Obrosky, D. Scott Jain, Rajiv Fine, Michael J. Jernigan, John A. TI The associations between organizational culture and knowledge, attitudes, and practices in a multicenter Veterans Affairs quality improvement initiative to prevent methicillin-resistant Staphylococcus aureus SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article DE Methicillin-resistant Staphylococcus aureus; Organizational culture; Prevention; Quality improvement; Survey ID INTENSIVE-CARE UNITS; HEALTH-CARE; ICU; PERCEPTIONS; INFECTIONS AB Background: Previous research demonstrates that organizational culture (OC) and knowledge, attitudes, and practices of health care personnel are associated with the overall success of infection control programs; however, little attention has been given to the relationships among these factors in contributing to the success of quality improvement programs. Methods: Cross-sectional surveys assessing OC and knowledge, attitudes, and practices related to methicillin-resistant Staphylococcus aureus (MRSA) were distributed to 16 medical centers participating in a Veterans Affairs MRSA prevention initiative in 2 time periods. Factor analysis was performed on the OC survey responses, and factor scores were generated. To assess associations between OC and knowledge, attitudes, and practices of health care personnel, regression analyses were performed overall and then stratified by job type. Results: The final analyzable sample included 2,314 surveys (43% completed by nurses, 9% by physicians, and 48% by other health care personnel). Three OC factors emerged accounting for 53% of the total variance: "Staff Engagement," "Overwhelmed/Stress-Chaos," and "Hospital Leadership." Overall, higher Staff Engagement was associated with greater knowledge scores, better hand hygiene practices, fewer reported barriers, and more positive attitudes. Higher Hospital Leadership scores were associated with better hand hygiene practices, fewer reported barriers, and more positive attitudes. Conversely, higher Overwhelmed/Stress-Chaos scores were associated with poorer reported prevention practices, more barriers, and less positive attitudes. When these associations were stratified by job type, there were significant associations between OC factors and knowledge for nurses only, between OC factors and practice items for nurses and other health care personnel, and between OC factors and the barriers and attitudes items for all job types. OC factors were not associated with knowledge and practices among physicians. Conclusions: Three OC factors-Staff Engagement, Overwhelmed/Stress-Chaos, and Hospital Leadership-were found to be significantly associated with individual health care personnel knowledge, attitudes, and self-reported practices regarding MRSA prevention. When developing a prevention intervention program, health care organizations should not only focus on the link between OC and the knowledge, attitudes, and practices of health care personnel, but also target programs based on health care personnel type to maximize their effectiveness. Published by Elsevier Inc. on behalf of Association for Professionals in Infection Control and Epidemiology, Inc. C1 [Sinkowitz-Cochran, Ronda L.; Harrison, Cassandra; Jernigan, John A.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. [Burkitt, Kelly H.; Gao, Shasha; Obrosky, D. Scott; Fine, Michael J.] VA Hlth Serv Res & Dev Serv, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Cuerdon, Timothy] VA Cent Off, Off Qual & Performance, Washington, DC USA. [Jain, Rajiv] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Fine, Michael J.] Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. RP Sinkowitz-Cochran, RL (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, 1600 Clifton Rd,MS A-31, Atlanta, GA 30333 USA. EM RLS7@cdc.gov NR 17 TC 15 Z9 15 U1 1 U2 13 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD MAR PY 2012 VL 40 IS 2 BP 138 EP 143 DI 10.1016/j.ajic.2011.04.332 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 899XK UT WOS:000300849800012 PM 21864944 ER PT J AU Thorndike, AN Sonnenberg, L Riis, J Barraclough, S Levy, DE AF Thorndike, Anne N. Sonnenberg, Lillian Riis, Jason Barraclough, Susan Levy, Douglas E. TI A 2-Phase Labeling and Choice Architecture Intervention to Improve Healthy Food and Beverage Choices SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SUGAR-SWEETENED BEVERAGES; PUBLIC-HEALTH; OBESITY; RESTAURANTS; IMPACT; INFORMATION; PREVENTION; PURCHASE; POINT; RISK AB Objectives. We assessed whether a 2-phase labeling and choice architecture intervention would increase sales of healthy food and beverages in a large hospital cafeteria. Methods. Phase 1 was a 3-month color-coded labeling intervention (red = unhealthy, yellow = less healthy, green = healthy). Phase 2 added a 3-month choice architecture intervention that increased the visibility and convenience of some green items. We compared relative changes in 3-month sales from baseline to phase 1 and from phase 1 to phase 2. Results. At baseline (977 793 items, including 199 513 beverages), 24.9% of sales were red and 42.2% were green. Sales of red items decreased in both phases (P<.001), and green items increased in phase 1 (P<.001). The largest changes occurred among beverages. Red beverages decreased 16.5% during phase 1 (P<.001) and further decreased 11.4% in phase 2 (P<.001). Green beverages increased 9.6% in phase 1 (P<.001) and further increased 4.0% in phase 2 (P<.001). Bottled water increased 25.8% during phase 2 (P<.001) but did not increase at 2 on-site comparison cafeterias (P<.001). Conclusions. A color-coded labeling intervention improved sales of healthy items and was enhanced by a choice architecture intervention. (Am J Public Health. 2012;102:527-533. doi:10.2105/AJPH.2011.300391) C1 [Thorndike, Anne N.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. [Sonnenberg, Lillian; Barraclough, Susan] Massachusetts Gen Hosp, Nutr Serv, Boston, MA 02114 USA. [Sonnenberg, Lillian; Barraclough, Susan] Massachusetts Gen Hosp, Food Serv, Boston, MA 02114 USA. [Riis, Jason] Harvard Univ, Sch Business, Mkt Unit, Boston, MA 02163 USA. [Levy, Douglas E.] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. RP Thorndike, AN (reprint author), Massachusetts Gen Hosp, Gen Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM athorndike@partners.org FU Harvard Clinical and Translational Science Center; National Center for Research Resources [1 UL1 RR025758-03]; National Heart, Lung, and Blood Institute [1 K23HL93221] FX Harvard Clinical and Translational Science Center, National Center for Research Resources (grant 1 UL1 RR025758-03) and the National Heart, Lung, and Blood Institute (grant 1 K23HL93221 to A.N.T.) supported this project. NR 28 TC 79 Z9 79 U1 7 U2 39 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 2012 VL 102 IS 3 BP 527 EP 533 DI 10.2105/AJPH.2011.300391 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 893EN UT WOS:000300338500028 PM 22390518 ER PT J AU Tariq, Z Ghose, A Bawany, MZ Saeed, B Mohamed, I Harmon, D AF Tariq, Zeeshan Ghose, Abhimanyu Bawany, Muhammad Z. Saeed, Bilal Mohamed, Iman Harmon, David TI A Case Report of Complete Remission of Pulmonary Metastases From Epithelioid Sarcoma to Navelbine Chemotherapy SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Article DE sarcoma; navelbine; pulmonary metastases; remission; chemotherapy; recurrence; relapse ID SOFT-TISSUE SARCOMAS AB Management of soft tissue sarcomas can be very challenging because they have a high rate of metastasis, especially to the lungs, and respond very poorly to the currently available chemotherapeutic drugs. We present a case of epithelioid sarcoma in which complete remission of pulmonary metastases was observed after treatment with a single agent, navelbine, a vinca alkaloid, and a potential therapeutic agent. The patient has been persistently free of metastases for 4 years since treatment with navelbine. Further studies are warranted to establish the role of navelbine for the treatment of soft tissue sarcoma and their metastases. C1 [Tariq, Zeeshan; Ghose, Abhimanyu; Bawany, Muhammad Z.; Saeed, Bilal] Univ Toledo, Dept Med, Toledo, OH 43614 USA. [Mohamed, Iman] Univ Toledo, Dept Hematol Oncol, Toledo, OH 43614 USA. [Harmon, David] Harvard Univ, Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02115 USA. RP Tariq, Z (reprint author), Univ Toledo, Dept Med, 3000 Arlington Ave, Toledo, OH 43614 USA. EM zeeshan.tariq@utoledo.edu NR 10 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 J9 AM J THER JI Am. J. Ther. PD MAR PY 2012 VL 19 IS 2 BP E95 EP E97 DI 10.1097/MJT.0b013e3181e70a50 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 906GW UT WOS:000301333900003 PM 20634676 ER PT J AU Manne, J Nakagawa, J Yamagata, Y Goehler, A Brownstein, JS Castro, MC AF Manne, Jennifer Nakagawa, Jun Yamagata, Yoichi Goehler, Alexander Brownstein, John S. Castro, Marcia C. TI Triatomine Infestation in Guatemala: Spatial Assessment after Two Rounds of Vector Control SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID TRYPANOSOMA-CRUZI INFECTION; CHAGAS-DISEASE VECTOR; CONTROL STRATEGIES; RHODNIUS-PROLIXUS; YUCATAN PENINSULA; DIMIDIATA; REDUVIIDAE; HEMIPTERA; ARGENTINA; PATTERNS AB In 2000, the Guatemalan Ministry of Health initiated a Chagas disease program to control Rhodnius prolixus and Triatoma dimidiata by periodic house spraying with pyrethroid insecticides. The aim of this study was to characterize infestation patterns and analyze the contribution of programmatic practices to these patterns. Spatial infestation patterns at three time points were identified using the Getis-Ord Gi*(d) test. Logistic regression was used to assess predictors of reinfestation after pyrethroid insecticide administration. Spatial analysis showed high and low clusters of infestation at three time points. After two rounds of spray, 178 communities persistently fell in high infestation clusters. A time lapse between rounds of vector control greater than 6 months was associated with 1.54 (95% confidence interval = 1.07-2.23) times increased odds of reinfestation after first spray, whereas a time lapse of greater than 1 year was associated with 2.66 (95% confidence interval = 1.85-3.83) times increased odds of reinfestation after first spray compared with localities where the time lapse was less than 180 days. The time lapse between rounds of vector control should remain under 1 year. Spatial analysis can guide targeted vector control efforts by enabling tracking of reinfestation hotspots and improved targeting of resources. C1 [Manne, Jennifer] Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. Univ Tokyo, Grad Sch Med, Dept Community & Global Hlth, Tokyo, Japan. Japanese Int Cooperat Agcy, Inst Int Cooperat, Tokyo, Japan. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. Childrens Hosp Boston, Computat Epidemiol Grp, Boston, MA USA. RP Manne, J (reprint author), Harvard Univ, Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave, Boston, MA 02115 USA. EM jmanne@post.harvard.edu FU David Rockefeller Center for Latin American Studies at Harvard University; Michael Von Clemm Family Fellowship; Harvard School of Public Health FX This research was supported by the David Rockefeller Center for Latin American Studies at Harvard University as well as the Michael Von Clemm Family Fellowship and the Andrew Spielman Memorial Travel Fellowship of the Harvard School of Public Health. NR 37 TC 10 Z9 10 U1 0 U2 4 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 2012 VL 86 IS 3 BP 446 EP 454 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 904AM UT WOS:000301166000013 PM 22403315 ER PT J AU Khoriaty, E McClain, CD Permaul, P Smith, ER Rachid, R AF Khoriaty, Evelyne McClain, Craig D. Permaul, Perdita Smith, Edward R. Rachid, Rima TI Intraoperative anaphylaxis induced by the gelatin component of thrombin-soaked gelfoam in a pediatric patient SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Letter ID TOPICAL BOVINE THROMBIN; SKIN-TEST; VACCINES C1 [Khoriaty, Evelyne; Rachid, Rima] Harvard Univ, Sch Med, Dept Med, Div Allergy & Immunol,Childrens Hosp Boston, Boston, MA 02115 USA. [McClain, Craig D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Anesthesiol, Boston, MA USA. [Permaul, Perdita] Massachusetts Gen Hosp, Dept Pediat, Div Pediat Pulm Allergy Immunol, Boston, MA 02114 USA. [Smith, Edward R.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurosurg, Boston, MA USA. RP Khoriaty, E (reprint author), Harvard Univ, Sch Med, Dept Med, Div Allergy & Immunol,Childrens Hosp Boston, Boston, MA 02115 USA. EM Rima.rachid@childrens.harvard.edu NR 9 TC 7 Z9 7 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 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD MAR PY 2012 VL 108 IS 3 BP 209 EP 210 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 899TG UT WOS:000300838500018 PM 22374209 ER PT J AU Forghanifard, MM Moaven, O Farshchian, M Montazer, M Raeisossadati, R Abdollahi, A Moghbeli, M Nejadsattari, T Parivar, K Abbaszadegan, MR AF Forghanifard, Mohammad Mahdi Moaven, Omeed Farshchian, Moein Montazer, Mehdi Raeisossadati, Reza Abdollahi, Abbas Moghbeli, Meysam Nejadsattari, Taher Parivar, Kazem Abbaszadegan, Mohammad Reza TI Expression Analysis Elucidates the Roles of MAML1 and Twist1 in Esophageal Squamous Cell Carcinoma Aggressiveness and Metastasis SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITION; TRANSCRIPTIONAL COACTIVATORS; BREAST-CANCER; NOTCH RECEPTORS; UP-REGULATION; E-CADHERIN; MASTERMIND; INVASION; IDENTIFICATION; RESISTANCE AB Epithelial-mesenchymal transition has recently attracted great attention in studying the malignant progression of cells through a converging pathway of oncogenesis and metastasis. Twist1 and Mastermind-like 1 (MAML1) are major regulators of EMT through different pathways. The aim of this study was to investigate the clinicopathological relevance of the expression of MAML-1 and Twist1 genes in esophageal squamous cell carcinoma (ESCC). Tumoral and corresponding normal tissues from 55 treatment-naive ESCC patients were subjected for expression analysis with quantitative real-time RT-PCR. Overexpression of MAML-1 and Twist1 were significantly associated with lymph node metastasis and the surgical staging of tumor. Overexpression of Twist1 was associated with tumor depth of invasion. Mean relative expression (MRE) of MAML1 was significantly higher in patients with metastasis to lymph nodes (3.07 +/- A 0.51 vs. 0.86 +/- A 0.58, P = .008). MRE of Twist1 was significantly higher in patients with invasion of tumor to adventitia (T3, T4) (1.97 +/- A 0.29 vs. 0.39 +/- A 0.73, P = .036). In advanced stages of tumor (stage III, IV), a significantly higher MRE of Twist1 (2.47 +/- A 0.41 vs. 1.25 +/- A 0.36, P = .035) and MAML1 (3.05 +/- A 0.45 vs. 1.07 +/- A 0.59, P = .021) mRNA was observed. We introduce Twist1 and MAML1 as new molecular markers of advanced tumor, which determine the characteristics and aggressive behavior of ESCC. Along with the emerging evidence of their role in different cellular processes and aberrations in various cancers, they are suggested as potentially interesting therapeutic targets to reverse a broad spectrum of functional aberrations that promote ESCC development. C1 [Forghanifard, Mohammad Mahdi; Nejadsattari, Taher; Parivar, Kazem] Islamic Azad Univ, Sci & Res Branch, Dept Biol, Tehran, Iran. [Forghanifard, Mohammad Mahdi] Islamic Azad Univ, Damghan Branch, Dept Biol, Damghan, Iran. [Moaven, Omeed] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. [Farshchian, Moein; Raeisossadati, Reza; Moghbeli, Meysam; Abbaszadegan, Mohammad Reza] Mashhad Univ Med Sci, Bu Ali Res Inst, Div Human Genet, Immunol Res Ctr, Mashhad, Iran. [Montazer, Mehdi] MUMS, Omid Hosp, Dept Pathol, Mashhad, Iran. [Abdollahi, Abbas] MUMS, Omid Hosp, Dept Surg, Mashhad, Iran. [Abbaszadegan, Mohammad Reza] Mashhad Univ Med Sci, Avicenna Res Inst, Div Human Genet, Mashhad 9196773117, Iran. RP Forghanifard, MM (reprint author), Islamic Azad Univ, Sci & Res Branch, Dept Biol, Tehran, Iran. EM abbaszadeganmr@mums.ac.ir RI Moghbeli, Meysam/Q-6582-2016; Montazer, Mehdi/C-7539-2011; OI Moghbeli, Meysam/0000-0001-9680-0309; Montazer, Mehdi/0000-0002-7759-3268; parivar, kazem/0000-0002-2836-9710; Moaven, Omeed/0000-0002-0560-0457 FU Islamic Azad University, Damghan Branch, Damghan, Iran [51423880299007] FX The authors gratefully acknowledge the review of our manuscript by Mr. Danial Afsharzadeh. The authors are also thankful to Ezzat Dadkhah, Azadeh A'rabi, and Martha Ghahraman at the Division of Human Genetics for their technical assistance. Additionally, we appreciate all our colleagues at the departments of Surgery and Pathology at Omid Hospital for their help in gathering and preparing tissue specimens. This study was supported by a grant (No. 51423880299007) from Islamic Azad University, Damghan Branch, Damghan, Iran. NR 33 TC 15 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2012 VL 19 IS 3 BP 743 EP 749 DI 10.1245/s10434-011-2074-8 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 892VN UT WOS:000300313800008 PM 22006371 ER PT J AU Rauh-Hain, JA Rodriguez, N Growdon, WB Goodman, AK Boruta, DM Horowitz, NS del Carmen, MG Schorge, JO AF Rauh-Hain, J. Alejandro Rodriguez, Noah Growdon, Whitfield B. Goodman, A. K. Boruta, David M., II Horowitz, Neil S. del Carmen, Marcela G. Schorge, John O. TI Primary Debulking Surgery Versus Neoadjuvant Chemotherapy in Stage IV Ovarian Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID EPITHELIAL OVARIAN; SURGICAL CYTOREDUCTION; PROGNOSTIC FACTORS; SURVIVAL; CARCINOMA; METAANALYSIS; MULTICENTER; RATIONALE; DISEASE AB Primary debulking surgery (PDS) has historically been the standard treatment for advanced ovarian cancer. Recent data appear to support a paradigm shift toward neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS). We hypothesized that stage IV ovarian cancer patients would likely benefit from NACT-IDS by achieving similar outcomes with less morbidity. Patients with stage IV epithelial ovarian cancer who underwent primary treatment between January 1, 1995 and December 31, 2007, were identified. Data were retrospectively extracted. Each patient record was evaluated to subclassify stage IV disease according to the sites of tumor dissemination at the time of diagnosis. The Kaplan-Meier method was used to compare overall survival (OS) data. A total of 242 newly diagnosed stage IV epithelial ovarian cancer patients were included in the final analysis; 176 women (73%) underwent PDS, 45 (18%) NACT-IDS, and 21 (9%) chemotherapy only. The frequency of achieving complete resection to no residual disease was significantly higher in patients with NACT-IDS versus PDS (27% vs. 7.5%; P < 0.001). When compared to women treated with NACT-IDS, women with PDS had longer admissions (12 vs. 8 days; P = 0.01), more frequent intensive care unit admissions (12% vs. 0%; P = 0.01), and a trend toward a higher rate of postoperative complications (27% vs. 15%; P = 0.08). The patients who received only chemotherapy had a median OS of 23 months, compared to 33 months in the NACT-IDS group and 29 months in the PDS group (P = 0.1). NACT-IDS for stage IV ovarian cancer resulted in higher rates of complete resection to no residual disease, less morbidity, and equivalent OS compared to PDS. C1 [Rauh-Hain, J. Alejandro; Growdon, Whitfield B.; Goodman, A. K.; Boruta, David M., II; del Carmen, Marcela G.; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02115 USA. [Rauh-Hain, J. Alejandro; Rodriguez, Noah; Horowitz, Neil S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Gynecol Oncol, Boston, MA 02115 USA. RP Rauh-Hain, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA 02115 USA. EM jschorge@partners.org NR 33 TC 28 Z9 32 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2012 VL 19 IS 3 BP 959 EP 965 DI 10.1245/s10434-011-2100-x PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 892VN UT WOS:000300313800037 PM 21994038 ER PT J AU Soiffer, RJ AF Soiffer, Robert J. TI To Induce, or Not to Induce, that is the (Still Unanswered) Question SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material ID MYELODYSPLASTIC SYNDROMES; TRANSPLANTATION C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Soiffer, RJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02215 USA. EM Robert_Soiffer@DFCI.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2012 VL 18 IS 3 BP 332 EP 333 DI 10.1016/j.bbmt.2012.01.002 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 904NK UT WOS:000301204800002 PM 22245597 ER PT J AU Chaleff, S Hurwitz, CA Chang, M Dahl, G Alonzo, TA Weinstein, H AF Chaleff, Stanley Hurwitz, Craig A. Chang, Myron Dahl, Gary Alonzo, Todd A. Weinstein, Howard TI Phase II study of 2-chlorodeoxyadenosine plus idarubicin for children with acute myeloid leukaemia in first relapse: a Paediatric Oncology Group study SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE paediatric; acute myeloid leukaemia; idarubicin; 2-CDA; phase 2 trial ID TRIAL; CLADRIBINE; CYTARABINE; CHEMOTHERAPY; COMBINATION; MALIGNANCIES; DEXRAZOXANE; DOXORUBICIN; RISK AB Relapse remains the leading cause of death in patients with acute myeloid leukaemia (AML). Relatively few new chemotherapy agents have been proven to be effective in this population. We report on a Phase 2 clinical trial using the novel combination of 2-chlorodeoxyadenosine (2-CDA) (8 mg/m(2) per d x 5 d) plus idarubicin (Ida) (10 mg/m(2) per d x 3 d). The study involved 109 paediatric patients with AML at first relapse, of whom 104 were available for analysis. The overall response rate was 51% (complete response [CR] + partial response) with a CR rate of 46%. 2-year event-free survival (EFS) and overall survival (OS) were 20% and 26%. The only significant variable in determining response, EFS and OS was duration of initial remission, with patients who had an initial remission >1 year having much worse outcomes overall (response rate 74% vs. 25%, EFS 8% vs. 37% and OS of 16% vs. 39%, P < 0.01 for all). There was an acceptable toxicity profile with one neurological event and no cardiac events observed. The most common grade 3-4 toxicities observed were neutropenia (59%) and thrombocytopenia (68%). This study demonstrated that the novel combination of 2-CDA/Ida was effective and should be considered for incorporation in front line therapy for children with AML. C1 [Chaleff, Stanley; Hurwitz, Craig A.] Maine Childrens Canc Program, Portland, ME USA. [Chang, Myron] Univ Florida, Miami, FL USA. [Dahl, Gary] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. [Alonzo, Todd A.] COG Biostat Ctr, Boston, MA USA. [Weinstein, Howard] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chaleff, S (reprint author), Maine Childrens Canc Program, 100 Campus Dr, Scarborough, ME 04074 USA. EM chales1@mmc.org FU NCI NIH HHS [U10 CA098543] NR 24 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2012 VL 156 IS 5 BP 649 EP 655 DI 10.1111/j.1365-2141.2011.08976.x PG 7 WC Hematology SC Hematology GA 901MU UT WOS:000300971800010 PM 22512017 ER PT J AU Geyer, MB Cairo, MS AF Geyer, Mark B. Cairo, Mitchell S. TI Starry sky SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE lymphoma; swelling; jaw; cyclophosphamide C1 [Geyer, Mark B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. [Cairo, Mitchell S.] New York Med Coll, Dept Pediat, Valhalla, NY 10595 USA. [Cairo, Mitchell S.] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. RP Geyer, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. EM mbgeyer@partners.org OI Geyer, Mark/0000-0001-5248-9117 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2012 VL 156 IS 6 BP 783 EP 783 DI 10.1111/j.1365-2141.2012.09036.x PG 1 WC Hematology SC Hematology GA 901MY UT WOS:000300972200014 ER PT J AU Thornton, E Krajewski, KM O'Regan, KN Giardino, AA Jagannathan, JP Ramaiya, N AF Thornton, E. Krajewski, K. M. O'Regan, K. N. Giardino, A. A. Jagannathan, J. P. Ramaiya, N. TI Imaging features of primary and secondary malignant tumours of the sacrum SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID RADIOLOGIC-PATHOLOGICAL CORRELATION; SACROCOCCYGEAL CHORDOMA; FDG-PET; SPINE; BONE; CHONDROSARCOMA; MANAGEMENT; DIAGNOSIS AB Malignant tumours of the sacrum may be primary or secondary. While sacral metastases are frequently encountered, a diagnostic dilemma can present when there is a single sacral bone tumour with no history or evidence of malignancy elsewhere in the body. Familiarity with the imaging features and clinical presentations of primary malignant bone tumours is helpful in narrowing the differential. This pictorial review will illustrate with both common and uncommon malignant sacral tumours CT, MRI and positron emission tomography/CT, highlighting the specific features of each. C1 [Thornton, E.; Krajewski, K. M.; O'Regan, K. N.; Giardino, A. A.; Jagannathan, J. P.; Ramaiya, N.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Thornton, E (reprint author), Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA. EM eavanthornton@gmail.com NR 26 TC 8 Z9 8 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD MAR PY 2012 VL 85 IS 1011 BP 279 EP 286 DI 10.1259/bjr/25247602 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 904UM UT WOS:000301223400019 PM 22167504 ER PT J AU Belting, M Almgren, P Manjer, J Hedblad, B Struck, J Wang, TJ Bergmann, A Melander, O AF Belting, Mattias Almgren, Peter Manjer, Jonas Hedblad, Bo Struck, Joachim Wang, Thomas J. Bergmann, Andreas Melander, Olle TI Vasoactive Peptides with Angiogenesis-Regulating Activity Predict Cancer Risk in Males SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CULTURED ENDOTHELIAL-CELLS; GROWTH-FACTOR; NATRIURETIC-PEPTIDE; BLOOD-PRESSURE; IMMUNOLUMINOMETRIC ASSAY; CARDIOVASCULAR EVENTS; TUMOR ANGIOGENESIS; AUTOCRINE GROWTH; ADRENOMEDULLIN; VASOPRESSIN AB Background: Tumor development requires angiogenesis, and antiangiogenesis has been introduced in the treatment of cancer patients; however, how the cardiovascular phenotype correlates with cancer risk remains ill-defined. Here, we hypothesized that vasoactive peptides previously implicated in angiogenesis regulation predict long-term cancer risk. Methods: We measured midregional proatrial natriuretic peptide (MR-proANP), proadrenomedullin (MR-proADM), and C-terminal preprovasopressin (copeptin) in fasting plasma from participants of the Malmo Diet and Cancer Study that were free from cancer prior to the baseline exam in 1991 to 1994 (1,768 males and 2,293 females). We used Cox proportional hazards models to determine the time to first cancer event in relation to baseline levels of vasoactive peptides during a median follow-up of 15 years. Results: First cancer events occurred in 366 males and in 368 females. In males, one SD increase of MR-proANP, copeptin, and MR-proADM was independently related to incident cancer [HR (95% CI)] by 0.85 (0.74-0.96), P = 0.012; 1.17 (1.04-1.32), P = 0.009; and 1.12 (0.99-1.26), P = 0.065, respectively, and a summed biomarker score identified an almost 2-fold difference in cancer risk between the top and bottom quartile (P < 0.001). In younger males, the biomarker score identified a more than 3-fold increase in risk between the top and bottom quartile (P < 0.001). Among females, we found no relationship between biomarkers and cancer incidence. Conclusions: Our data suggest that vasoactive peptide biomarkers predict cancer risk in males, particularly in younger males. Impact: Our findings may have implications for cancer risk prediction and present novel, potentially drug modifiable, mechanisms underlying cancer development. Cancer Epidemiol Biomarkers Prev; 21(3); 513-22. (C) 2012 AACR. C1 [Melander, Olle] Skane Univ Hosp, Dept Clin Sci, CRC, Ctr Emergency Med, SE-20502 Malmo, Sweden. [Hedblad, Bo; Melander, Olle] Skane Univ Hosp, Ctr Emergency Med, Lund, Sweden. [Belting, Mattias] Lund Univ, Sect Oncol, Dept Clin Sci, Lund, Sweden. [Almgren, Peter; Manjer, Jonas; Hedblad, Bo; Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Belting, Mattias] Skane Univ Hosp, Dept Oncol, SE-20502 Malmo, Sweden. [Belting, Mattias] Skane Univ Hosp, Dept Oncol, Lund, Sweden. [Struck, Joachim] Thermo Fisher Sci, BRAHMS Biomarkers, Hennigsdorf, Germany. [Bergmann, Andreas] Waltraut Bergmann Fdn, Hohen Neuendorf, Germany. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Cardiovasc Res Ctr, Boston, MA USA. [Wang, Thomas J.] Broad Inst Harvard & MIT, Cambridge, England. [Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Melander, O (reprint author), Skane Univ Hosp, Dept Clin Sci, CRC, Ctr Emergency Med, Entrance 72,Bldg 91,Level 12, SE-20502 Malmo, Sweden. EM olle.melander@med.lu.se FU Swedish Cancer Society; Swedish Research Council; Lund University Hospital; Medical Faculty, Lund University; national health services (ALF); Swedish Heart and Lung Foundation; Malmo University Hospital; Albert Pahlsson Research Foundation; Crafoord Foundation; Gunnar Nilsson Cancer Foundation; Region Skane; King Gustaf V and Queen Victoria Foundation; Marianne and Marcus Wallenberg Foundation; Knut and Alice Wallenberg Foundation FX This work was supported by The Swedish Cancer Society (to M. Belting), the Swedish Research Council (O. Melander and M. Belting); the Lund University Hospital donation funds (M. Belting); the Medical Faculty, Lund University (O. Melander and M. Belting); the Governmental funding of clinical research within the national health services (ALF; O. Melander and M. Belting), the Swedish Heart and Lung Foundation (O. Melander), Malmo University Hospital (O. Melander), the Albert Pahlsson Research Foundation (O. Melander), the Crafoord Foundation (O. Melander and M. Belting), the Gunnar Nilsson Cancer Foundation (M. Belting), Region Skane (O. Melander), the King Gustaf V and Queen Victoria Foundation (O. Melander), the Marianne and Marcus Wallenberg Foundation (O. Melander), and the Knut and Alice Wallenberg Foundation (O. Melander). NR 53 TC 5 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2012 VL 21 IS 3 BP 513 EP 522 DI 10.1158/1055-9965.EPI-11-0840 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 905PG UT WOS:000301284100016 PM 22267286 ER PT J AU Li, H Bitler, BG Vathipadiekal, V Maradeo, ME Slifker, M Creasy, CL Tummino, PJ Cairns, P Birrer, MJ Zhang, RG AF Li, Hua Bitler, Benjamin G. Vathipadiekal, Vinod Maradeo, Marie E. Slifker, Michael Creasy, Caretha L. Tummino, Peter J. Cairns, Paul Birrer, Michael J. Zhang, Rugang TI ALDH1A1 Is a Novel EZH2 Target Gene in Epithelial Ovarian Cancer Identified by Genome-Wide Approaches SO CANCER PREVENTION RESEARCH LA English DT Article ID GROUP PROTEIN EZH2; STEM-CELLS; ALDEHYDE DEHYDROGENASE; DNA METHYLATION; PROSTATE-CANCER; REPRESSION; SENESCENCE; CHROMATIN; PLURIPOTENT; EXPRESSION AB Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy in the United States. EZH2 silences gene expression through trimethylating lysine 27 on histone H3 (H3K27Me3). EZH2 is often overexpressed in EOC and has been suggested as a target for EOC intervention. However, EZH2 target genes in EOC remain poorly understood. Here, we mapped the genomic loci occupied by EZH2/H3K27Me3 using chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) and globally profiled gene expression in EZH2-knockdown EOC cells. Cross-examination of gene expression and ChIP-seq revealed a list of 60 EZH2 direct target genes whose expression was upregulated more than 1.5-fold upon EZH2 knockdown. For three selected genes (ALDH1A1, SSTR1, and DACT3), we validated their upregulation upon EZH2 knockdown and confirmed the binding of EZH2/H3K27Me3 to their genomic loci. Furthermore, the presence of H3K27Me3 at the genomic loci of these EZH2 target genes was dependent upon EZH2. Interestingly, expression of ALDH1A1, a putative marker for EOC stem cells, was significantly downregulated in high-grade serous EOC (n = 53) compared with ovarian surface epithelial cells (n 10, P < 0.001). Notably, expression of ALDH1A1 negatively correlated with expression of EZH2 (n 63, Spearman r = -0.41, P < 0.001). Thus, we identified a list of 60 EZH2 target genes and established that ALDH1A1 is a novel EZH2 target gene in EOC cells. Our results suggest a role for EZH2 in regulating EOC stem cell equilibrium via regulation of ALDH1A1 expression. Cancer Prev Res; 5(3); 484-91. (C) 2011 AACR. C1 [Li, Hua; Bitler, Benjamin G.; Zhang, Rugang] Fox Chase Canc Ctr, Womens Canc Program, Philadelphia, PA 19111 USA. [Li, Hua; Bitler, Benjamin G.; Zhang, Rugang] Fox Chase Canc Ctr, Epigenet & Progenitor Cell Keystone Program, Philadelphia, PA 19111 USA. [Maradeo, Marie E.; Cairns, Paul] Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA. [Slifker, Michael] Fox Chase Canc Ctr, Biostat & Bioinformat Facil, Philadelphia, PA 19111 USA. [Vathipadiekal, Vinod; Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Vathipadiekal, Vinod; Birrer, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. [Creasy, Caretha L.; Tummino, Peter J.] GlaxoSmithKline Pharmaceut Inc, Oncol R&D, Canc Epigenet Discovery Performance Unit, Collegeville, PA USA. RP Zhang, RG (reprint author), Fox Chase Canc Ctr, Womens Canc Program, W446,333 Cottman Ave, Philadelphia, PA 19111 USA. EM rugang.zhang@fccc.edu OI Vathipadiekal, Vinod/0000-0002-8181-6890 FU NCI FCCC-UPenn ovarian cancer SPORE [P50 CA083638]; SPORE career development award; DOD [OC093420]; NCI [CA-009035-35] FX This work was supported in part by a NCI FCCC-UPenn ovarian cancer SPORE (P50 CA083638) pilot project and SPORE career development award ( to R. Zhang) and a DOD ovarian cancer academy award (OC093420 to R. Zhang). B. G.Bitler is supported by an NCI postdoctoral training grant (CA-009035-35). R. Zhang is an Ovarian Cancer Research Fund (OCRF) Liz Tilberis Scholar. NR 37 TC 21 Z9 22 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAR PY 2012 VL 5 IS 3 BP 484 EP 491 DI 10.1158/1940-6207.CAPR-11-0414 PG 8 WC Oncology SC Oncology GA 901ST UT WOS:000300987800015 PM 22144423 ER PT J AU Yeo, KK Mahmud, E Armstrong, EJ Bennett, WE Shunk, KA MacGregor, JS Li, ZM Low, RI Rogers, JH AF Yeo, Khung Keong Mahmud, Ehtisham Armstrong, Ehrin J. Bennett, William E. Shunk, Kendrick A. MacGregor, John S. Li, Zhongmin Low, Reginald I. Rogers, Jason H. TI Contemporary clinical characteristics, treatment, and outcomes of angiographically confirmed coronary stent thrombosis: Results from a multicenter California registry SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE stent; coronary intervention; thrombosis ID DRUG-ELUTING STENTS; DEATH MASTER FILE; INTRAVASCULAR ULTRASOUND; MYOCARDIAL-INFARCTION; BARE-METAL; IMPLANTATION; SIROLIMUS; PREDICTORS; RESISTANCE; TRIALS AB Objectives: To describe the contemporary treatment and outcomes for patients with angiographically confirmed (definite) stent thrombosis (ST). Background: Limited data are available on contemporary treatment patterns and outcomes of patients with ST in the United States. Methods: In this multicenter California registry, consecutive cases of definite ST over 5 years were identified. Clinical characteristics, in-hospital outcomes, and long-term survival are reported. Results: One hundred and sixty five consecutive episodes of ST were identified in 153 patients from January 2005 to February 2010. The distribution of acute (=24 hr), subacute (24 hr to 30 days), late (30 days to 1 year), and very late (=1 year) ST was 3.9%, 21.8%, 17.6%, and 50.3%, respectively. Only 41.2% of patients were on dual antiplatelet therapy at the time of presentation, while 22.4% of patients were on none. Of the 61.4% of patients treated with restenting, 71.1% of them received a drug-eluting stent. Procedural success was 88.1%, and in-hospital death, stroke, and CABG occurred in 5.5%, 0.6%, and 6.1% of subjects, respectively. All-cause mortality at 1 year was 14.3%. Although female gender, diabetes mellitus (DM), bifurcation disease, ejection fraction <40%, and cardiogenic shock at the time of presentation were associated with an increased risk of in-hospital mortality, only DM (P = 0.047) and bifurcation disease (P = 0.027) remained independent predictors of in-hospital death. Conclusion: In-hospital mortality from definite ST is lower than previously reported, but long-term mortality remains high. DM and bifurcation disease, but not type of percutaneous therapy, are independently associated with in-hospital mortality. (c) 2011 Wiley Periodicals, Inc. C1 [Yeo, Khung Keong; Li, Zhongmin; Low, Reginald I.; Rogers, Jason H.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. [Mahmud, Ehtisham; Bennett, William E.] Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. [Armstrong, Ehrin J.; Shunk, Kendrick A.] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA. [Shunk, Kendrick A.] San Francisco VA Med Ctr, San Francisco, CA USA. [MacGregor, John S.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. RP Rogers, JH (reprint author), Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. EM jason.rogers@ucdmc.ucdavis.edu FU Boston Scientific; Abbott Vascular; Sanofi Aventis FX Dr Low is on the advisory board of Abbott Vascular and Boston Scientific. Dr Rogers is a consultant for Volcano, Medtronic, Cordis, and Boston Scientific. Dr Mahmud is on the Speakers Bureau for Medtronic and Eli Lilly. He is a consultant for Eli Lilly and has research support from Boston Scientific, Abbott Vascular, and Sanofi Aventis. NR 18 TC 14 Z9 15 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAR 1 PY 2012 VL 79 IS 4 BP 550 EP 556 DI 10.1002/ccd.23011 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 897PE UT WOS:000300664300005 PM 21563289 ER PT J AU Milbury, CA Correll, M Quackenbush, J Rubio, R Makrigiorgos, GM AF Milbury, Coren A. Correll, Mick Quackenbush, John Rubio, Renee Makrigiorgos, G. Mike TI COLD-PCR Enrichment of Rare Cancer Mutations prior to Targeted Amplicon Resequencing SO CLINICAL CHEMISTRY LA English DT Article ID RESOLUTION MELTING ANALYSIS; IARC TP53 DATABASE; SEQUENCING SYSTEM; DNA MUTATIONS; KRAS MUTATION; LUNG-CANCER; SENSITIVITY; GENOME; BREAST; QUANTIFICATION AB BACKGROUND: Despite widespread interest in next-generation sequencing (NGS), the adoption of personalized clinical genomics and mutation profiling of cancer specimens is lagging, in part because of technical limitations. Tumors are genetically heterogeneous and often contain normal/stromal cells, features that lead to low-abundance somatic mutations that generate ambiguous results or reside below NGS detection limits, thus hindering the clinical sensitivity/specificity standards of mutation calling. We applied COLD-PCR (coamplification at lower denaturation temperature PCR), a PCR methodology that selectively enriches variants, to improve the detection of unknown mutations before NGS-based amplicon resequencing. METHODS: We used both COLD-PCR and conventional PCR (for comparison) to amplify serially diluted mutation-containing cell-line DNA diluted into wildtype DNA, as well as DNA from lung adenocarcinoma and colorectal cancer samples. After amplification of TP53 (tumor protein p53), KRAS (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog), IDH1 [isocitrate dehydrogenase 1(NADP(+)), soluble], and EGFR(epidermal growth factor receptor) gene regions, PCR products were pooled for library preparation, bar-coded, and sequenced on the Illumina HiSeq 2000. RESULTS: In agreement with recent findings, sequencing errors by conventional targeted-amplicon approaches dictated a mutation-detection limit of approximately 1%-2%. Conversely, COLD-PCR amplicons enriched mutations above the error-related noise, enabling reliable identification of mutation abundances of approximately 0.04%. Sequencing depth was not a large factor in the identification of COLD-PCR-enriched mutations. For the clinical samples, several missense mutations were not called with conventional amplicons, yet they were clearly detectable with COLD-PCR amplicons. Tumor heterogeneity for the TP53 gene was apparent. CONCLUSIONS: As cancer care shifts toward personalized intervention based on each patient's unique genetic abnormalities and tumor genome, we anticipate that COLD-PCR combined with NGS will elucidate the role of mutations in tumor progression, enabling NGS-based analysis of diverse clinical specimens within clinical practice. (C) 2011 American Association for Clinical Chemistry C1 [Milbury, Coren A.; Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div DNA Repair & Genome Stabil,Dept Radiat Oncol, Boston, MA 02115 USA. [Correll, Mick; Quackenbush, John; Rubio, Renee] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Makrigiorgos, G. Mike] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Phys & Biophys,Dept Radiat Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, Level L2,75 Francis St, Boston, MA 02115 USA. EM mmakrigiorgos@lroc.harvard.edu FU National Cancer Institute [T32-CA009078, R21-CA-151164]; Dana- Farber Cancer Institute, NIH [1U01CA151118]; National Science Foundation; NIH; JCRT Foundation FX Research Funding: C. A. Milbury, National Cancer Institute training grant T32-CA009078; J. Quackenbush, Dana- Farber Cancer Institute, NIH (grant no. 1U01CA151118), and the National Science Foundation; G. M. Makrigiorgos, NIH departmental funds, JCRT Foundation, and Innovative Molecular Analysis Technologies Program of the National Cancer Institute (grant nos. R21-CA-151164 and R21-CA-151164). NR 45 TC 29 Z9 31 U1 3 U2 11 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2012 VL 58 IS 3 BP 580 EP 589 DI 10.1373/clinchem.2011.176198 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 901AU UT WOS:000300934900017 PM 22194627 ER PT J AU Chavalitdhamrong, D Jensen, DM Singh, B Kovacs, TOG Han, SH Durazo, F Saab, S Gornbein, JA AF Chavalitdhamrong, Disaya Jensen, Dennis M. Singh, Bhavneet Kovacs, Thomas O. G. Han, Steven H. Durazo, Francisco Saab, Sammy Gornbein, Jeffrey A. TI Capsule Endoscopy Is Not as Accurate as Esophagogastroduodenoscopy in Screening Cirrhotic Patients for Varices SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Detection; Surgery; Esophagus; Cirrhosis; Hepatitis ID ESOPHAGEAL-VARICES; PORTAL-HYPERTENSION; DIAGNOSIS; HEMORRHAGE; EGD AB BACKGROUND & AIMS: Esophagogastroduodenoscopy (EGD) is the standard technique for screening cirrhotic patients for high-risk varices and other significant upper gastrointestinal lesions (HRVLs). We investigated whether esophageal capsule endoscopy (ECE) is as convenient and accurate as EGD for the detection of HRVLs. METHODS: We analyzed data from 65 cirrhotic patients without prior upper gastrointestinal bleeding who were examined for varices and HRVLs by ECE and EGD (both procedures were performed on the same day). EGD was performed by 2 physicians (75% of patients were unsedated) who used standard grading for esophageal and gastric varices, portal hypertensive gastropathy, and HRVLs. Coded capsule tracings were read by 2 investigators, blinded to the EGD findings, using standard grading. RESULTS: The median procedure time for EGD (with or without biopsy collection) was 3 minutes, compared with 20 minutes for ECE. The overall accuracy for diagnosis of esophageal varices was 63.2% +/- 5.9%; for detection of esophageal varices red marks was 68.8% +/- 5.4%; and for diagnosis of other HRVLs was 51.5% +/- 4.2%. The interobserver agreement in the diagnosis of esophageal varices was 90.8%; in the detection of esophageal varices red marks was 86.2%; and in the diagnosis of other HRVLs was 7.3%. CONCLUSIONS: ECE is not as accurate as EGD in the diagnosis of esophageal varices and red markings or in grading esophageal varices. Moreover, ECE had poor accuracy in grading portal hypertensive gastropathy and detecting ulcers, gastric varices, and other significant upper gastrointestinal lesions. It took significantly longer to perform ECE and interpret the results than for EGD. These findings do not support ECE as a preferred tool for screening esophageal varices and HRVLs. C1 [Chavalitdhamrong, Disaya; Jensen, Dennis M.; Singh, Bhavneet; Kovacs, Thomas O. G.] Digest Dis Res Ctr, Ctr Ulcer Res & Educ, Los Angeles, CA USA. [Jensen, Dennis M.; Kovacs, Thomas O. G.; Han, Steven H.; Durazo, Francisco; Saab, Sammy] Univ Calif Los Angeles, Med Ctr, Div Digest Dis, Los Angeles, CA 90024 USA. [Jensen, Dennis M.; Kovacs, Thomas O. G.; Han, Steven H.] Greater Los Angeles VA Healthcare Ctr, Res Sect, Los Angeles, CA USA. [Jensen, Dennis M.; Kovacs, Thomas O. G.; Han, Steven H.] Greater Los Angeles VA Healthcare Ctr, GI Hepatol Sect, Los Angeles, CA USA. [Gornbein, Jeffrey A.] Univ Calif Los Angeles, Biostat Consulting Unit, Los Angeles, CA USA. RP Chavalitdhamrong, D (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM disaya104@gmail.com FU Ethicon Endosurgery, National Institutes of Health [K24-DK002650]; Center for Ulcer Research and Education [P30-DK041301]; Pentax (Montvale, NJ) FX This study was partially supported by research funds from Ethicon Endosurgery, National Institutes of Health grant (K24-DK002650), the Center for Ulcer Research and Education Human Studies Core (P30-DK041301), and an equipment grant from Pentax (Montvale, NJ). NR 14 TC 4 Z9 5 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2012 VL 10 IS 3 BP 254 EP U156 DI 10.1016/j.cgh.2011.11.027 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 904YA UT WOS:000301234100019 PM 22155754 ER PT J AU Strachan, M Gros, DF Yuen, E Ruggiero, KJ Foa, EB Acierno, R AF Strachan, Martha Gros, Daniel F. Yuen, Erica Ruggiero, Kenneth J. Foa, Edna B. Acierno, Ron TI Home-based telehealth to deliver evidence-based psychotherapy in veterans with PTSD SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE PTSD; Prolonged exposure; Psychotherapy; Home-based telehealth ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; IRAQ; AFGHANISTAN; DEPLOYMENT; SERVICES; THERAPY; TRIALS; ISSUES; RISK AB Although medical service delivery via home-based telehealth technology (HBT) is gaining wider acceptance in managing chronic illnesses such as diabetes or chronic obstructive pulmonary disease, few studies have tested HBT applications of psychotherapy. Clinicians, administrators, and researchers question whether delivering psychotherapeutic services to patients in their homes via video-conferencing technology compromises patient safety, potency of treatment, or data security. Despite these concerns. HBT service delivery may increase access to evidence-based psychotherapies for veterans with posttraumatic stress disorder (PTSD), who may be less willing or less able to receive weekly treatment at a VA medical center or outpatient clinic due to symptom severity or other similar barriers to care. Indeed, although combat-exposed service members endorse high rates of psychiatric disorders, few appear to initiate mental health services or receive an adequate dose of treatment. Thus, using HBT technologies to administer evidence-based therapies remains uncharted territory in both the clinical and research arenas. This manuscript describes an ongoing four year randomized controlled trial comparing in-person Prolonged Exposure (PE) - a specialized evidence-based psychotherapy for PTSD - and PE delivered via HBT, with a particular focus on the selection, application, and strengths/weaknesses of HBT procedures. (C) 2011 Elsevier Inc. All rights reserved. C1 [Strachan, Martha; Gros, Daniel F.; Yuen, Erica; Ruggiero, Kenneth J.; Acierno, Ron] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [Strachan, Martha; Gros, Daniel F.; Yuen, Erica; Ruggiero, Kenneth J.; Acierno, Ron] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Foa, Edna B.] Univ Penn, Ctr Treatment & Study Anxiety, Philadelphia, PA 19104 USA. RP Strachan, M (reprint author), Med Univ S Carolina, Dept Psychiat, 67 President St,2-S, Charleston, SC 29425 USA. EM stracham@musc.edu RI Schueter, nicos/A-3625-2014 FU Veterans Affairs Health Services Research and Development [NCT01102764]; VAMC [REA08-261] FX This work was supported by a grant from Veterans Affairs Health Services Research and Development awarded to R. Acierno (NCT01102764). In addition, some authors are members of the Ralph H. Johnson VAMC Research Enhancement Award Program (REA08-261; PI: Leonard Egede, M.D.). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. There are no conflicts of interest to disclose. NR 33 TC 20 Z9 20 U1 4 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAR PY 2012 VL 33 IS 2 BP 402 EP 409 DI 10.1016/j.cct.2011.11.007 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 901JA UT WOS:000300962000020 PM 22101225 ER EF