FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Virani, SS Brautbar, A Davis, BC Nambi, V Hoogeveen, RC Sharrett, AR Coresh, J Mosley, TH Morrisett, JD Catellier, DJ Folsom, AR Boerwinkle, E Ballantyne, CM AF Virani, Salim S. Brautbar, Ariel Davis, Brian C. Nambi, Vijay Hoogeveen, Ron C. Sharrett, A. Richey Coresh, Josef Mosley, Thomas H. Morrisett, Joel D. Catellier, Diane J. Folsom, Aaron R. Boerwinkle, Eric Ballantyne, Christie M. TI Associations Between Lipoprotein(a) Levels and Cardiovascular Outcomes in Black and White Subjects The Atherosclerosis Risk in Communities (ARIC) Study SO CIRCULATION LA English DT Article DE cardiovascular diseases; ethnic groups; lipoproteins; race; risk factors ID CORONARY-HEART-DISEASE; APOLIPOPROTEIN-A-I; PLASMA LIPOPROTEIN(A); MYOCARDIAL-INFARCTION; LP(A) LIPOPROTEIN; ARTERY-DISEASE; ELEVATED LIPOPROTEIN(A); CAROTID ATHEROSCLEROSIS; SERUM-LIPOPROTEIN; CHOLESTEROL AB Background-On the basis of studies with limited statistical power, lipoprotein(a) [Lp(a)] is not considered a risk factor for cardiovascular disease (CVD) in blacks. We evaluated associations between Lp(a) and incident CVD events in blacks and whites in the Atherosclerosis Risk in Communities (ARIC) study. Methods and Results-Plasma Lp(a) was measured in blacks (n = 3467) and whites (n = 9851). Hazards ratios (HRs) for incident CVD events (coronary heart disease and ischemic strokes) were calculated. Lp(a) levels were higher with wider interindividual variation in blacks (median [interquartile range], 12.8 [7.1-21.7] mg/dL) than whites (4.3 [1.7-9.5] mg/dL; P < 0.0001). At 20 years of follow-up, 676 CVD events occurred in blacks, and 1821 events occurred in whites. Adjusted HRs (95% confidence interval) per race-specific 1-SD-greater log-transformed Lp(a) were 1.13 (1.04-1.23) for incident CVD, 1.11 (1.00-1.22) for incident coronary heart disease, and 1.21 (1.06-1.39) for ischemic strokes in blacks. For whites, the respective HRs (95% confidence intervals) were 1.09 (1.04-1.15), 1.10 (1.05-1.16), and 1.07 (0.97-1.19). Quintile analyses showed that risk for incident CVD was graded but statistically significant only for the highest compared with the lowest quintile (HR [95% confidence interval], 1.35 [1.06-1.74] for blacks and 1.27 [1.10-1.47] for whites). Similar results were obtained with the use of Lp(a) cutoffs of <= 10 mg/dL, >10 to <= 20 mg/dL, >20 to <= 30 mg/dL, and >30 mg/dL. Conclusions-Lp(a) levels were positively associated with CVD events. Associations were at least as strong, with a larger range of Lp(a) concentrations, in blacks compared with whites. (Circulation. 2012;125:241-249.) C1 [Virani, Salim S.; Brautbar, Ariel; Nambi, Vijay; Hoogeveen, Ron C.; Morrisett, Joel D.; Ballantyne, Christie M.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA. [Virani, Salim S.; Brautbar, Ariel; Nambi, Vijay; Hoogeveen, Ron C.; Morrisett, Joel D.; Ballantyne, Christie M.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. [Virani, Salim S.] Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Davis, Brian C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Sharrett, A. Richey; Coresh, Josef] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS USA. [Catellier, Diane J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Ballantyne, CM (reprint author), Baylor Coll Med, Dept Med, Sect Cardiovasc Res, 6565 Fannin,MS A-601,Suite A656, Houston, TX 77030 USA. EM cmb@bcm.tmc.edu OI Virani, Salim/0000-0001-9541-6954 FU National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; Department of Veterans Affairs [CDA-09-028]; National Institutes of Health [5K23HL096893-02]; Merck; National Football League Charities; Gillson Longenbaugh Foundation; Gulf Coast Regional Foundation; Abbott; AstraZeneca; Bristol-Myers Squibb; diaDexus; GlaxoSmithKline; Kowa; Novartis; Roche; Sanofi-Synthelabo; Takeda; National Institutes of Health; American Diabetes Association; American Heart Association FX The ARIC study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Dr Virani is supported by a Department of Veterans Affairs Health Services Research and Development Service Career Development Award (CDA-09-028). Dr Nambi is supported by a National Institutes of Health grant (5K23HL096893-02).; The authors report the following disclosures: Salim Virani: research support from Merck and National Football League Charities (all grants to the institution and not individual); speakers bureau for Abbott (discontinued November 2010). Vijay Nambi: research grants from Gillson Longenbaugh Foundation and Gulf Coast Regional Foundation; consultant/virtual advisory board for Roche; speakers bureau for the American Heart Association; research collaboration with GE, Tomtec, Medipattern (no financial support); editor for Vascular Ultrasound Today; and officer for the American Society of Echocardiology. Christie M. Ballantyne: grant/research support (all paid to institution, not individual) from Abbott, AstraZeneca, Bristol-Myers Squibb, diaDexus, GlaxoSmithKline, Kowa, Merck, Novartis, Roche, Sanofi-Synthelabo, Takeda, National Institutes of Health, American Diabetes Association, American Heart Association; consultant for Abbott, Adnexus, Amylin, AstraZeneca, Bristol-Myers Squibb, Esperion, Genentech, GlaxoSmithKline, Idera Pharma, Kowa, Merck, Novartis, Omthera, Resverlogix, Roche, Sanofi-Synthelabo, Takeda; speakers bureau for Abbott, GlaxoSmithKline, Merck; honoraria from Abbott, AstraZeneca, GlaxoSmithKline, Merck, Sanofi-Synthelabo, Takeda. NR 41 TC 64 Z9 67 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 17 PY 2012 VL 125 IS 2 BP 241 EP U154 DI 10.1161/CIRCULATIONAHA.111.045120 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879HZ UT WOS:000299321600013 PM 22128224 ER PT J AU Eikermann-Haerter, K Lee, JH Yuzawa, I Liu, CH Zhou, ZP Shin, HK Zheng, Y Qin, T Kurth, T Waeber, C Ferrari, MD van den Maagdenberg, AMJM Moskowitz, MA Ayata, C AF Eikermann-Haerter, Katharina Lee, Jeong Hyun Yuzawa, Izumi Liu, Christina H. Zhou, Zhipeng Shin, Hwa Kyoung Zheng, Yi Qin, Tao Kurth, Tobias Waeber, Christian Ferrari, Michel D. van den Maagdenberg, Arn M. J. M. Moskowitz, Michael A. Ayata, Cenk TI Migraine Mutations Increase Stroke Vulnerability by Facilitating Ischemic Depolarizations SO CIRCULATION LA English DT Article DE calcium channels; cortical spreading depression; migraine disorders; stroke ID FAMILIAL HEMIPLEGIC MIGRAINE; CORTICAL SPREADING DEPRESSION; CA(V)2.1 CALCIUM-CHANNELS; FOCAL CEREBRAL-ISCHEMIA; POPULATION-BASED SAMPLE; SUBARACHNOID HEMORRHAGE; PERIINFARCT DEPOLARIZATIONS; CARDIOVASCULAR-DISEASE; MOUSE MODEL; BRAIN-LESIONS AB Background-Migraine is an independent risk factor for stroke. Mechanisms underlying this association are unclear. Familial hemiplegic migraine (FHM), a migraine subtype that also carries an increased stroke risk, is a useful model for common migraine phenotypes because of shared aura and headache features, trigger factors, and underlying glutamatergic mechanisms. Methods and Results-Here, we show that FHM type 1 (FHM1) mutations in Ca(V)2.1 voltage-gated Ca2+ channels render the brain more vulnerable to ischemic stroke. Compared with wild-type mice, 2 FHM1 mutant mouse strains developed earlier onset of anoxic depolarization and more frequent peri-infarct depolarizations associated with rapid expansion of infarct core on diffusion-weighted magnetic resonance imaging and larger perfusion deficits on laser speckle flowmetry. Cerebral blood flow required for tissue survival was higher in the mutants, leading to infarction with milder ischemia. As a result, mutants developed larger infarcts and worse neurological outcomes after stroke, which were selectively attenuated by a glutamate receptor antagonist. Conclusions-We propose that enhanced susceptibility to ischemic depolarizations akin to spreading depression predisposes migraineurs to infarction during mild ischemic events, thereby increasing the stroke risk. (Circulation. 2012;125:335-345.) C1 [Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yuzawa, Izumi; Zhou, Zhipeng; Shin, Hwa Kyoung; Zheng, Yi; Qin, Tao; Waeber, Christian; Moskowitz, Michael A.; Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. [Liu, Christina H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging & Transcr, Charlestown, MA 02129 USA. [Liu, Christina H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol,NeuroRepair Lab, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv & Neurosci Intens Care Unit,Dept Neur, Charlestown, MA 02129 USA. [Zhou, Zhipeng] Guilin Med Coll, Affiliated Hosp, Dept Radiol, Guilin, Peoples R China. [Shin, Hwa Kyoung] Pusan Natl Univ, Sch Korean Med, Div Meridian & Struct Med, Yangsan, South Korea. [Kurth, Tobias] Univ Bordeaux, INSERM, U708, Bordeaux, France. [Kurth, Tobias] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. [Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.] Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. [van den Maagdenberg, Arn M. J. M.] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands. RP Ayata, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM cayata@partners.org RI Kurth, Tobias/A-9243-2012; Lee, Jeong Hyun/G-1676-2013; Waeber, Christian/A-8333-2009; OI Kurth, Tobias/0000-0001-7169-2620; Lee, Jeong Hyun/0000-0003-0504-0119; Waeber, Christian/0000-0001-6078-0027; Liu, Christina/0000-0002-5723-177X FU American Heart Association [09GRNT2060416, 10SDG2610275]; National Institutes of Health (NIH) [NS061505, NS055104, NS35611, NS057556, DA024235, DA026108]; Deane Institute for Integrative Research in Stroke and Atrial Fibrillation; Netherlands Organization for Scientific Research [903-52-291, Vici 918.56.602]; EU EUROHEAD [LSHM-CT-2004-504837]; Centre for Medical Systems Biology; National Research Foundation of Korea; Ministry of Education, Science and Technology [2009-0066654]; Harvard Catalyst/The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University FX This work was supported by the American Heart Association (09GRNT2060416, 10SDG2610275); National Institutes of Health (NIH; NS061505, NS055104, NS35611, NS057556, DA024235, DA026108); Deane Institute for Integrative Research in Stroke and Atrial Fibrillation; Netherlands Organization for Scientific Research (903-52-291 and Vici 918.56.602; Spinoza 2009); EU EUROHEAD grant (LSHM-CT-2004-504837); Centre for Medical Systems Biology in the framework of the Netherlands Genomics Initiative; Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2009-0066654); and 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). NR 58 TC 59 Z9 61 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 17 PY 2012 VL 125 IS 2 BP 335 EP U345 DI 10.1161/CIRCULATIONAHA.111.045096 PG 24 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879HZ UT WOS:000299321600023 PM 22144569 ER PT J AU Robbins, CS Chudnovskiy, A Rauch, PJ Figueiredo, JL Iwamoto, Y Gorbatov, R Etzrodt, M Weber, GF Ueno, T van Rooijen, N Mulligan-Kehoe, MJ Libby, P Nahrendorf, M Pittet, MJ Weissleder, R Swirski, FK AF Robbins, Clinton S. Chudnovskiy, Aleksey Rauch, Philipp J. Figueiredo, Jose-Luiz Iwamoto, Yoshiko Gorbatov, Rostic Etzrodt, Martin Weber, Georg F. Ueno, Takuya van Rooijen, Nico Mulligan-Kehoe, Mary Jo Libby, Peter Nahrendorf, Matthias Pittet, Mikael J. Weissleder, Ralph Swirski, Filip K. TI Extramedullary Hematopoiesis Generates Ly-6C(high) Monocytes That Infiltrate Atherosclerotic Lesions SO CIRCULATION LA English DT Article DE atherosclerosis; imaging; immune system; immunology; macrophages ID COLONY-STIMULATING FACTOR; SPLENIC MARGINAL ZONE; DENDRITIC CELLS; DEFICIENT MICE; B-LYMPHOCYTES; INFLAMMATION; MACROPHAGES; STEM; SPLEEN; ORIGIN AB Background-Atherosclerotic lesions are believed to grow via the recruitment of bone marrow-derived monocytes. Among the known murine monocyte subsets, Ly-6C(high) monocytes are inflammatory, accumulate in lesions preferentially, and differentiate. Here, we hypothesized that the bone marrow outsources the production of Ly-6C(high) monocytes during atherosclerosis. Methods and Results-Using murine models of atherosclerosis and fate-mapping approaches, we show that hematopoietic stem and progenitor cells progressively relocate from the bone marrow to the splenic red pulp, where they encounter granulocyte macrophage colony-stimulating factor and interleukin-3, clonally expand, and differentiate to Ly-6C(high) monocytes. Monocytes born in such extramedullary niches intravasate, circulate, and accumulate abundantly in atheromata. On lesional infiltration, Ly-6C(high) monocytes secrete inflammatory cytokines, reactive oxygen species, and proteases. Eventually, they ingest lipids and become foam cells. Conclusions-Our findings indicate that extramedullary sites supplement the hematopoietic function of the bone marrow by producing circulating inflammatory cells that infiltrate atherosclerotic lesions. (Circulation. 2012; 125: 364-374.) C1 [Robbins, Clinton S.; Swirski, Filip K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Robbins, Clinton S.; Chudnovskiy, Aleksey; Rauch, Philipp J.; Figueiredo, Jose-Luiz; Iwamoto, Yoshiko; Gorbatov, Rostic; Etzrodt, Martin; Weber, Georg F.; Ueno, Takuya; Nahrendorf, Matthias; Pittet, Mikael J.; Weissleder, Ralph; Swirski, Filip K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [van Rooijen, Nico] Free Univ Amsterdam, Med Ctr, Dept Mol Cell Biol, Amsterdam, Netherlands. [Mulligan-Kehoe, Mary Jo] Dartmouth Med Sch, Dartmouth Hitchcock Heart & Vasc Res Ctr, Dept Surg, Lebanon, NH USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Swirski, FK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM robbins.clinton@mgh.harvard.edu; fswirski@mgh.harvard.edu RI Etzrodt, Martin/P-3325-2015 OI Etzrodt, Martin/0000-0003-1928-3904 FU National Institutes of Health [1R01 HL095612, U01 HL080731, P50 CA86355, U24 CA092782, P01-A154904, 2R01 HL069948]; American Heart Association; Massachusetts General Hospital ECOR; Boehringer Ingelheim Fonds; German Research Foundation FX This work was supported in part by National Institutes of Health grants 1R01 HL095612 (Dr Swirski), U01 HL080731, P50 CA86355, U24 CA092782, P01-A154904 (to Dr Weissleder), and 2R01 HL069948 (to Dr Mulligan-Kehoe). Dr Robbins was supported by the American Heart Association postdoctoral fellowship and the Massachusetts General Hospital ECOR Postdoctoral Award. P.J. Rauch was supported by the Boehringer Ingelheim Fonds. Dr Weber was supported by the German Research Foundation. NR 54 TC 146 Z9 149 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 17 PY 2012 VL 125 IS 2 BP 364 EP U415 DI 10.1161/CIRCULATIONAHA.111.061986 PG 25 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879HZ UT WOS:000299321600026 PM 22144566 ER PT J AU Moukarbel, GV Bhatt, DL AF Moukarbel, George V. Bhatt, Deepak L. TI Antiplatelet Therapy and Proton Pump Inhibition Clinician Update SO CIRCULATION LA English DT Article ID DOSE ACETYLSALICYLIC-ACID; CONCOMITANT USE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; ADVERSE OUTCOMES; ARTERY-DISEASE; CLOPIDOGREL; RISK; CORONARY; ASPIRIN C1 [Moukarbel, George V.; Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. RP Bhatt, DL (reprint author), 1400 VFW PKWY, Boston, MA 02132 USA. EM DLBHATTMD@post.harvard.edu NR 34 TC 19 Z9 21 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 17 PY 2012 VL 125 IS 2 BP 375 EP 380 DI 10.1161/CIRCULATIONAHA.111.019745 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879HZ UT WOS:000299321600027 PM 22249527 ER PT J AU Kahn, CR Roth, J AF Kahn, C. Ronald Roth, Jesse TI Rosalyn Sussman Yalow (1921-2011) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Biographical-Item C1 [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Roth, Jesse] Hofstra Univ, Feinstein Inst Med Res, Hofstra N Shore LIJ Sch Med, Manhasset, NY 11030 USA. [Roth, Jesse] Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. EM c.ronald.kahn@joslin.harvard.edu NR 1 TC 1 Z9 1 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 17 PY 2012 VL 109 IS 3 BP 669 EP 670 DI 10.1073/pnas.1120470109 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 877CK UT WOS:000299154000011 ER PT J AU Tse, JM Cheng, G Tyrrell, JA Wilcox-Adelman, SA Boucher, Y Jain, RK Munn, LL AF Tse, Janet M. Cheng, Gang Tyrrell, James A. Wilcox-Adelman, Sarah A. Boucher, Yves Jain, Rakesh K. Munn, Lance L. TI Mechanical compression drives cancer cells toward invasive phenotype SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mechanobiology; solid stress; collective migration; metastasis ID SHEAR-STRESS; MALIGNANT PHENOTYPE; GROWTH; MIGRATION; MORPHOGENESIS; POLARITY; ADHESION; FLOW; MICROENVIRONMENT; PROLIFERATION AB Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such stress affects tumor cell behavior. Here we show that compressive stress stimulates migration of mammary carcinoma cells. The enhanced migration is accomplished by a subset of "leader cells" that extend filopodia at the leading edge of the cell sheet. Formation of these leader cells is dependent on cell micro-organization and is enhanced by compressive stress. Accompanied by fibronectin deposition and stronger cell-matrix adhesion, the transition to leader-cell phenotype results in stabilization of persistent actomyosin-independent cell extensions and coordinated migration. Our results suggest that compressive stress accumulated during tumor growth can enable coordinated migration of cancer cells by stimulating formation of leader cells and enhancing cell-substrate adhesion. This novel mechanism represents a potential target for the prevention of cancer cell migration and invasion. C1 [Tse, Janet M.; Cheng, Gang; Tyrrell, James A.; Boucher, Yves; Jain, Rakesh K.; Munn, Lance L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Tse, Janet M.; Cheng, Gang; Tyrrell, James A.; Boucher, Yves; Jain, Rakesh K.; Munn, Lance L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tse, Janet M.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Tyrrell, James A.] Thomson Reuters, Corp Res & Dev, New York, NY 10007 USA. [Wilcox-Adelman, Sarah A.] Boston Biomed Res Inst, Watertown, MA 02472 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu; munn@steele.mgh.harvard.edu RI Tyrrell, James/A-6359-2010; Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU National Institutes of Health [P01CA080124, HL64240] FX We thank A. Jain and Dr. T. R. Sodunke for their help with microfabrication, Dr. S.-S. Chae for his help with molecular manipulations, and Dr. F. R. Miller for providing the 67NR and 4T1 cells. Funding for this work was provided by National Institutes of Health Grants P01CA080124 (to R.K.J., L. L. M., and Y.B.) and HL64240 (to L.L.M.). NR 50 TC 98 Z9 98 U1 1 U2 43 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 JAN 17 PY 2012 VL 109 IS 3 BP 911 EP 916 DI 10.1073/pnas.1118910109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 877CK UT WOS:000299154000055 PM 22203958 ER PT J AU zur Wiesch, JS Ciuffreda, D Lewis-Ximenez, L Kasprowicz, V Nolan, BE Streeck, H Aneja, J Reyor, LL Allen, TM Lohse, AW McGovern, B Chung, RT Kwok, WW Kim, AY Lauer, GM AF zur Wiesch, Julian Schulze Ciuffreda, Donatella Lewis-Ximenez, Lia Kasprowicz, Victoria Nolan, Brian E. Streeck, Hendrik Aneja, Jasneet Reyor, Laura L. Allen, Todd M. Lohse, Ansgar W. McGovern, Barbara Chung, Raymond T. Kwok, William W. Kim, Arthur Y. Lauer, Georg M. TI Broadly directed virus-specific CD4(+) T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INTERFERON-ALPHA THERAPY; ACUTE HCV INFECTION; EX-VIVO ANALYSIS; IMMUNE-RESPONSES; NONSTRUCTURAL PROTEIN-3; SPONTANEOUS-RECOVERY; ANTIVIRAL TREATMENT; PD-1 EXPRESSION; CD4+T CELLS; CD8(+) AB Vigorous proliferative CD4(+) T cell responses are the hallmark of spontaneous clearance of acute hepatitis C virus (HCV) infection, whereas comparable responses are absent in chronically evolving infection. Here, we comprehensively characterized the breadth, specificity, and quality of the HCV-specific CD4(+) T cell response in 31 patients with acute HCV infection and varying clinical outcomes. We analyzed in vitro T cell expansion in the presence of interleukin-2, and ex vivo staining with HCV peptide-loaded MHC class II tetramers. Surprisingly, broadly directed HCV-specific CD4(+) T cell responses were universally detectable at early stages of infection, regardless of the clinical outcome. However, persistent viremia was associated with early proliferative defects of the HCV-specific CD4(+) T cells, followed by rapid deletion of the HCV-specific response. Only early initiation of antiviral therapy was able to preserve CD4(+) T cell responses in acute, chronically evolving infection. Our results challenge the paradigm that HCV persistence is the result of a failure to prime HCV-specific CD4(+) T cells. Instead, broadly directed HCV-specific CD4(+) T cell responses are usually generated, but rapid exhaustion and deletion of these cells occurs in the majority of patients. The data further suggest a short window of opportunity to prevent the loss of CD4(+) T cell responses through antiviral therapy. C1 [zur Wiesch, Julian Schulze; Ciuffreda, Donatella; Nolan, Brian E.; Aneja, Jasneet; Reyor, Laura L.; Chung, Raymond T.; Lauer, Georg M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Aneja, Jasneet; Reyor, Laura L.; Kim, Arthur Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kasprowicz, Victoria; Streeck, Hendrik; Allen, Todd M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. [zur Wiesch, Julian Schulze; Lohse, Ansgar W.] Univ Klinikum Hamburg Eppendorf, Med Klin 1, D-20246 Hamburg, Germany. [zur Wiesch, Julian Schulze] Leibniz Inst Expt Virol, Heinrich Pette Inst, D-20251 Hamburg, Germany. [McGovern, Barbara] Tufts Univ, Sch Med, Lemuel Shattuck Hosp, Jamaica Plain, MA 02130 USA. [Kwok, William W.] Benaroya Res Inst Virginia Mason, Seattle, WA 98101 USA. [Lewis-Ximenez, Lia] Fundacao Oswaldo Cruz, Lab Hepatites Virais, Inst Oswaldo Cruz, BR-21040 Rio De Janeiro, RJ, Brazil. RP Lauer, GM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM glauer@helix.mgh.harvard.edu RI Allen, Todd/F-5473-2011 FU Howard Hughes Medical Institute; Deutsche Forschungsgemeinschaft [Schu 2482/1-1, SFB 841 A6]; Swiss National Science Foundation; National Institutes of Health [U19-AI066345, U19-AI082630, R01-AI067926-01] FX This study was supported by the Howard Hughes Medical Institute (J. Schulze zur Wiesch), Deutsche Forschungsgemeinschaft Schu 2482/1-1, SFB 841 A6 (J. Schulze zur Wiesch), Swiss National Science Foundation (D. Ciuffreda), and National Institutes of Health grants U19-AI066345 (L. Lewis-Ximenez, T.M. Allen, A.Y. Kim, and G.M. Lauer), U19-AI082630 (R. T. Chung and G. M. Lauer), and R01-AI067926-01 (T.M. Allen). NR 66 TC 58 Z9 58 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 16 PY 2012 VL 209 IS 1 BP 61 EP 75 DI 10.1084/jem.20100388 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 885ZO UT WOS:000299820200007 ER PT J AU Leuschner, F Rauch, PJ Ueno, T Gorbatov, R Marinelli, B Lee, WW Dutta, P Wei, Y Robbins, C Iwamoto, Y Sena, B Chudnovskiy, A Panizzi, P Keliher, E Higgins, JM Libby, P Moskowitz, MA Pittet, MJ Swirski, FK Weissleder, R Nahrendorf, M AF Leuschner, Florian Rauch, Philipp J. Ueno, Takuya Gorbatov, Rostic Marinelli, Brett Lee, Won Woo Dutta, Partha Wei, Ying Robbins, Clinton Iwamoto, Yoshiko Sena, Brena Chudnovskiy, Aleksey Panizzi, Peter Keliher, Edmund Higgins, John M. Libby, Peter Moskowitz, Michael A. Pittet, Mikael J. Swirski, Filip K. Weissleder, Ralph Nahrendorf, Matthias TI Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-ASSOCIATED MACROPHAGES; DENDRITIC CELLS; BONE-MARROW; SPLENIC RESERVOIR; PROGENITOR CELLS; PROSTATE-CANCER; INFLAMMATION; HETEROGENEITY; APOPTOSIS; SUBSETS AB Monocytes (Mo) and macrophages (M Phi) are emerging therapeutic targets in malignant, cardiovascular, and autoimmune disorders. Targeting of Mo/M Phi and their effector functions without compromising innate immunity's critical defense mechanisms first requires addressing gaps in knowledge about the life cycle of these cells. Here we studied the source, tissue kinetics, and clearance of Mo/M Phi in murine myocardial infarction, a model of acute inflammation after ischemic injury. We found that a) Mo tissue residence time was surprisingly short (20 h); b) Mo recruitment rates were consistently high even days after initiation of inflammation; c) the sustained need of newly made Mo was fostered by extramedullary monocytopoiesis in the spleen; d) splenic monocytopoiesis was regulated by IL-1.; and e) the balance of cell recruitment and local death shifted during resolution of inflammation. Depending on the experimental approach, we measured a 24 h Mo/M Phi exit rate from infarct tissue between 5 and 13% of the tissue cell population. Exited cells were most numerous in the blood, liver, and spleen. Abrogation of extramedullary monocytopoiesis proved deleterious for infarct healing and accelerated the evolution of heart failure. We also detected rapid Mo kinetics in mice with stroke. These findings expand our knowledge of Mo/M Phi flux in acute inflammation and provide the groundwork for novel anti-inflammatory strategies for treating heart failure. C1 [Leuschner, Florian; Rauch, Philipp J.; Ueno, Takuya; Gorbatov, Rostic; Marinelli, Brett; Lee, Won Woo; Dutta, Partha; Robbins, Clinton; Iwamoto, Yoshiko; Sena, Brena; Chudnovskiy, Aleksey; Panizzi, Peter; Keliher, Edmund; Higgins, John M.; Pittet, Mikael J.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Leuschner, Florian; Rauch, Philipp J.; Ueno, Takuya; Gorbatov, Rostic; Marinelli, Brett; Lee, Won Woo; Dutta, Partha; Robbins, Clinton; Iwamoto, Yoshiko; Sena, Brena; Chudnovskiy, Aleksey; Panizzi, Peter; Keliher, Edmund; Higgins, John M.; Pittet, Mikael J.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Lee, Won Woo] Seoul Natl Univ, Bundang Hosp, Dept Nucl Med, Songnam 463707, South Korea. [Wei, Ying; Moskowitz, Michael A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. [Panizzi, Peter] Auburn Univ, Harrison Sch Pharm, Dept Pharmacal Sci, Auburn, AL 36849 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu RI Lee, Won Woo/J-5589-2012; OI Panizzi, Peter/0000-0003-0141-8807 FU National Heart, Lung, and Blood Institute [R01HL095629, R01HL096576]; American Heart Association [SDG0835623D]; Translational Program of Excellence in Nanotechnology [R24-CA92782, U01-HL080731/HHSN268201000044C]; Deutsche Herzstiftung e. V.; Boehringer Ingelheim; Korea Research Foundation [KRF-2009-013-E00027] FX This work was funded in part by grants from the National Heart, Lung, and Blood Institute (R01HL095629 and R01HL096576) and the American Heart Association (SDG0835623D) to M. Nahrendorf; R24-CA92782 and Translational Program of Excellence in Nanotechnology U01-HL080731/HHSN268201000044C to R. Weissleder; Deutsche Herzstiftung e. V. to F. Leuschner; Boehringer Ingelheim Fonds to P.J. Rauch; and the Korea Research Foundation Grant (KRF-2009-013-E00027) to W.W. Lee. NR 54 TC 158 Z9 159 U1 2 U2 15 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 16 PY 2012 VL 209 IS 1 BP 123 EP 137 DI 10.1084/jem.20111009 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 885ZO UT WOS:000299820200011 PM 22213805 ER PT J AU Rehman, Y Rosenberg, JE AF Rehman, Yasser Rosenberg, Jonathan E. TI Abiraterone acetate: oral androgen biosynthesis inhibitor for treatment of castration-resistant prostate cancer SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Review DE CRPC; abiraterone; CYP17; inhibitors; androgens; castration resistant prostate cancer ID I CLINICAL-TRIAL; DEPRIVATION THERAPY; RECEPTOR MUTATIONS; PHASE-II; CYP17; DOCETAXEL; MECHANISM; KETOCONAZOLE; P450C17; GROWTH AB Prostate cancer is the second leading cause of cancer death in men in the US and Europe. The treatment of advanced-stage prostate cancer has been androgen deprivation. Medical castration leads to decreased production of testosterone and dihydrotestosterone by the testes, but adrenal glands and even prostate cancer tissue continue to produce androgens, which eventually leads to continued prostate cancer growth despite castrate level of androgens. This stage is known as castrate-resistant prostate cancer (CRPC), which continues to be a challenge to treat. Addition of androgen antagonists to hormonal deprivation has been successful in lowering the prostate-specific antigen levels further, but has not actually translated into life-prolonging options. The results of several contemporary studies have continued to demonstrate activation of the androgen receptor as being the key factor in the continued growth of prostate cancer. Blockade of androgen production by nongonadal sources has led to clinical benefit in this setting. One such agent is abiraterone acetate, which significantly reduces androgen production by blocking the enzyme, cytochrome P450 17 alpha-hydroxylase (CYP17). This has provided physicians with another treatment option for patients with CRPC. The landscape for prostate cancer treatment has changed with the approval of cabazitaxel, sipuleucel-T and abiraterone. Here we provide an overview of abiraterone acetate, its mechanism of action, and its potential place for therapy in CRPC. C1 [Rehman, Yasser] UMass Mem Healthcare, Div Hosp Med, Worcester, MA 01605 USA. [Rosenberg, Jonathan E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Rehman, Y (reprint author), UMass Mem Healthcare, Div Hosp Med, 119 Belmont St, Worcester, MA 01605 USA. EM yasser_rehman@dfci.harvard.edu NR 26 TC 14 Z9 15 U1 1 U2 9 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-8881 J9 DRUG DES DEV THER JI Drug Des. Dev. Ther. PD JAN 16 PY 2012 VL 6 BP 13 EP 18 DI 10.2147/DDDT.S15850 PG 6 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 880EJ UT WOS:000299387300001 PM 22291466 ER PT J AU Chen, JJ Salat, DH Rosas, HD AF Chen, J. Jean Salat, David H. Rosas, H. Diana TI Complex relationships between cerebral blood flow and brain atrophy in early Huntington's disease SO NEUROIMAGE LA English DT Article DE Huntington's disease (HD); Pulsed arterial-spin labeling (PASL); Magnetic resonance imaging (MRI); Cerebral blood flow (CBF); Cortical thickness ID POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE IMAGES; BASAL GANGLIA VOLUME; SPIN-LABELING MRI; MORPHOMETRIC-ANALYSIS; ALZHEIMERS-DISEASE; GLUCOSE-METABOLISM; ENDOTHELIAL-CELLS; MATTER CHANGES; CAG REPEAT AB Alterations in cerebral blood flow (CBF) may play an important role in the pathophysiology of neurodegenerative disorders such as Huntington's disease (HD). While a few reports have suggested reductions in CBF in HD, little is known about their extent and whether, or how, they might be related to atrophy and to clinical symptoms. We used pulsed arterial-spin labeling MRI in conjunction with high-resolution anatomical MRI to non-invasively measure regional CBF in 17 early stage HD subjects and 41 age- and gender-matched healthy controls. We found profound yet heterogeneous CBF reductions in the cortex, extending to the sensorimotor, paracentral, inferior temporal and lateral occipital regions, with sparing of the neighboring postcentral gyrus, insula and medial occipital areas. As expected, CBF in subcortical regions was also profoundly reduced, and to a similar degree. Unexpectedly, however, the association between CBF reductions and regional atrophy was complex, the two being directly associated in certain areas but not with others. In contrast, CBF was associated with performance on the Stroop, suggesting a potentially important role for alterations in CBF in cognitive deficits in HD. The work described here may have broad-reaching implications for our understanding of HD pathogenesis, progression and emerging therapies. (C) 2011 Elsevier Inc. All rights reserved. C1 [Chen, J. Jean; Salat, David H.; Rosas, H. Diana] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging,Dept Neurol, Charlestown, MA 02129 USA. RP Chen, JJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging,Dept Neurol, Charlestown, MA 02129 USA. EM jjchen@nmr.mgh.harvard.edu RI Chen, J. Jean/A-2846-2013 OI Chen, J. Jean/0000-0001-5469-7542 FU NIH [R01NR010827, NS042861, NS058793, P41RR14075]; Canadian Institutes of Health Research FX This research was supported by NIH grants R01NR010827, NS042861, NS058793, and P41RR14075, as well as by fellowship funding from the Canadian Institutes of Health Research (J. J. C.). We also thank Mr. Robert McInnis for aiding the neuropsychological assessments. NR 91 TC 15 Z9 15 U1 3 U2 10 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 JAN 16 PY 2012 VL 59 IS 2 BP 1043 EP 1051 DI 10.1016/j.neuroimage.2011.08.112 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 864AY UT WOS:000298210600022 PM 21945790 ER PT J AU Panizzon, MS Hauger, RL Eaves, LJ Chen, CH Dale, AM Eyler, LT Fischl, B Fennema-Notestine, C Franz, CE Grant, MD Jacobson, KC Jak, AJ Lyons, MJ Mendoza, SP Neale, MC Prom-Wormley, E Seidman, LJ Tsuang, MT Xian, H Kremen, WS AF Panizzon, Matthew S. Hauger, Richard L. Eaves, Lindon J. Chen, Chi-Hua Dale, Anders M. Eyler, Lisa T. Fischl, Bruce Fennema-Notestine, Christine Franz, Carol E. Grant, Michael D. Jacobson, Kristen C. Jak, Amy J. Lyons, Michael J. Mendoza, Sally P. Neale, Michael C. Prom-Wormley, Elizabeth Seidman, Larry J. Tsuang, Ming T. Xian, Hong Kremen, William S. TI Genetic influences on hippocampal volume differ as a function of testosterone level in middle-aged men SO NEUROIMAGE LA English DT Article DE Heritability; Hippocampal volume; Testosterone; Twin study; Aging ID VIETNAM ERA TWIN; MESSENGER-RNA EXPRESSION; ENDOGENOUS SEX-HORMONES; ANDROGEN RECEPTOR GENE; CAG REPEAT POLYMORPHISM; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; RAT-BRAIN; OLDER MEN AB The hippocampus expresses a large number of androgen receptors: therefore, in men it is potentially vulnerable to the gradual age-related decline of testosterone levels. In the present study we sought to elucidate the nature of the relationship between testosterone and hippocampal volume in a sample of middle-aged male twins (average age 55.8 years). We found no evidence for a correlation between testosterone level and hippocampal volume, as well as no indication of shared genetic influences. However, a significant moderating effect of testosterone on the genetic and environmental determinants of hippocampal volume was observed. Genetic influences on hippocampal volume increased substantially as a function of increasing testosterone level, while environmental influences either decreased or remained stable. These findings provide evidence for an apparent gene-by-hormone interaction on hippocampal volume. To the best of our knowledge, this is the first study to demonstrate that the heritability of a brain structure in adults may be modified by an endogenous biological factor. (C) 2011 Elsevier Inc. All rights reserved. C1 [Panizzon, Matthew S.; Hauger, Richard L.; Chen, Chi-Hua; Eyler, Lisa T.; Fennema-Notestine, Christine; Franz, Carol E.; Jak, Amy J.; Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Hauger, Richard L.; Eyler, Lisa T.; Jak, Amy J.] San Diego Vet Adm Healthcare Syst, San Diego, CA 92161 USA. [Eaves, Lindon J.; Neale, Michael C.; Prom-Wormley, Elizabeth] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USA. [Dale, Anders M.; Fennema-Notestine, Christine] Univ Calif San Diego, Dept Radiol, San Diego, CA 92093 USA. [Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Fischl, Bruce] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fischl, Bruce; Seidman, Larry J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Grant, Michael D.; Lyons, Michael J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Jacobson, Kristen C.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. [Mendoza, Sally P.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. [Tsuang, Ming T.; Kremen, William S.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Xian, Hong] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Panizzon, MS (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,MC 0738, La Jolla, CA 92093 USA. EM mspanizz@ucsd.edu RI Jacobson, Kristen/D-2064-2009; OI Fennema-Notestine, Christine/0000-0002-6527-6361; Lyons, Michael/0000-0001-6516-9219; Prom-Wormley, Elizabeth/0000-0001-9230-9723 FU National Institutes of Health/National Institute on Aging (NIH/NIA) [R01 AG18386, RO1 AG18384, RO1 AG22381, RO1 AG22982]; U.S. Department of Veterans Affairs FX The VETSA project is supported by National Institutes of Health/National Institute on Aging (NIH/NIA) Grants R01 AG18386, RO1 AG18384, RO1 AG22381, and RO1 AG22982. The U.S. Department of Veterans Affairs has provided support for the development and maintenance of the Vietnam Era Twin Registry. Numerous organizations have provided invaluable assistance, including VA Cooperative Studies Program; Department of Defense; National Personnel Records Center, National Archives and Records Administration; the Internal Revenue Service; National Institutes of Health; National Opinion Research Center; National Research Council, National Academy of Sciences; the Institute for Survey Research, Temple University; Schulman, Ronca, and Bucuvalas, Inc. Most importantly, we gratefully acknowledge the cooperation and participation of the members of the Vietnam Era Twin Registry and their families. Without their contribution this research would not have been possible. NR 103 TC 12 Z9 12 U1 0 U2 7 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 JAN 16 PY 2012 VL 59 IS 2 BP 1123 EP 1131 DI 10.1016/j.neuroimage.2011.09.044 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 864AY UT WOS:000298210600033 PM 21983185 ER PT J AU Stoodley, CJ Valera, EM Schmahmann, JD AF Stoodley, Catherine J. Valera, Eve M. Schmahmann, Jeremy D. TI Functional topography of the cerebellum for motor and cognitive tasks: An fMRI study SO NEUROIMAGE LA English DT Article DE Cerebellum; Functional MRI; Cognition; Sensorimotor; Topography ID VERBAL WORKING-MEMORY; MENTAL ROTATION; SPEECH-PERCEPTION; BRAIN ACTIVATION; NETWORKS; MRI; TRANSFORMATIONS; CONNECTIVITY; EMOTION; GENERATION AB Anatomical, clinical and imaging findings suggest that the cerebellum is engaged in cognitive and affective functions as well as motor control. Evidence from converging modalities also indicates that there is a functional topography in the human cerebellum for overt control of movement vs. higher functions, such that the cerebellum can be divided into zones depending on connectivity with sensorimotor vs. multimodal association cortices. Using functional MRI, we show that regions active during overt movement differ from those involved in higher-level language, spatial processing and working memory tasks. Nine healthy participants each completed five tasks in order to determine the relative activation patterns for the different paradigms. Right-handed finger-tapping activated right cerebellar lobules IV-V and VIII, consistent with descriptions of the cerebellar homunculi. Verb generation engaged right cerebellar lobules VI-Crus I and a second cluster in lobules VIIB-VIIIA. Mental rotation activation peaks were localized to medial left cerebellar lobule VII (Crus II). A 2-back working memory task activated bilateral regions of lobules VI-VII. Viewing arousing vs. neutral images did not reliably activate the cerebellum or cerebral limbic areas in this study. The cerebellar functional topography identified in this study reflects the involvement of different cerebro-cerebellar circuits depending on the demands of the task being performed: overt movement activated sensorimotor cortices along with contralateral cerebellar lobules IV-V and VIII, whereas more cognitively demanding tasks engaged prefrontal and parietal cortices along with cerebellar lobules VI and VII. These findings provide further support for a cerebellar role in both motor and cognitive tasks, and better establish the existence of functional subregions in the cerebellum. Future studies are needed to determine the exact contribution of the cerebellum - and different cerebro-cerebellar circuits - to task performance. (C) 2011 Elsevier Inc. All rights reserved. C1 [Stoodley, Catherine J.] American Univ, Dept Psychol, Washington, DC 20016 USA. [Stoodley, Catherine J.; Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Cognit Behav Neurol Unit, Boston, MA 02114 USA. [Stoodley, Catherine J.; Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Stoodley, Catherine J.; Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Lab Neuroanat & Cerebellar Neurobiol, Boston, MA 02114 USA. [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Ataxia Unit, Dept Neurol, Boston, MA 02114 USA. [Valera, Eve M.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Program, Charlestown, MA 02129 USA. [Valera, Eve M.] Massachusetts Gen Hosp, Dept Psychiat, Clin Program Pediat Psychopharmacol & Addult Atte, Charlestown, MA 02129 USA. [Valera, Eve M.] Massachusetts Gen Hosp, Dept Psychiat, Res Program Pediat Psychopharmacol & Addult Atten, Charlestown, MA 02129 USA. [Valera, Eve M.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Stoodley, CJ (reprint author), American Univ, Dept Psychol, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. EM stoodley@american.edu RI Stoodley, Catherine/P-2081-2016 OI Stoodley, Catherine/0000-0003-2629-0213 FU National Center for Research Resources [P41RR14075]; Massachusetts General Hospital; National Institutes of Health [071535]; Birmingham Foundation; MINDlink foundation FX This study was supported in part by the National Center for Research Resources (P41RR14075); the Massachusetts General Hospital Fund for Medical Discovery (CJS); the National Institutes of Health (071535, EMV); the Birmingham Foundation (JDS) and the MINDlink foundation (JDS). The authors would like to thank Larry Seidman for the use of the n-back task, Peter Hansen for providing stimuli for the mental rotation task, Janet Sherman for help with the psychometric test battery, and Joanna Willms and Jason MacMore for assistance with data collection. NR 82 TC 196 Z9 201 U1 6 U2 59 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 JAN 16 PY 2012 VL 59 IS 2 BP 1560 EP 1570 DI 10.1016/j.neuroimage.2011.08.065 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 864AY UT WOS:000298210600077 PM 21907811 ER PT J AU Melancon, BJ Lamers, AP Bridges, TM Sulikowski, GA Utley, TJ Sheffler, DJ Noetzel, MJ Morrison, RD Daniels, JS Niswender, CM Jones, CK Conn, PJ Lindsley, CW Wood, MR AF Melancon, Bruce J. Lamers, Alexander P. Bridges, Thomas M. Sulikowski, Gary A. Utley, Thomas J. Sheffler, Douglas J. Noetzel, Meredith J. Morrison, Ryan D. Daniels, J. Scott Niswender, Colleen M. Jones, Carrie K. Conn, P. Jeffrey Lindsley, Craig W. Wood, Michael R. TI Development of a more highly selective M-1 antagonist from the continued optimization of the MLPCN Probe ML012 SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Muscarinic acetylcholine receptor 1; M-1; Antagonist; ML012; VU0415248 ID MUSCARINIC ACETYLCHOLINE-RECEPTORS; XANOMELINE; MODULATORS; AGONIST; GENES; MICE AB This Letter describes the continued optimization of an MLPCN probe molecule (ML012) through an iterative parallel synthesis approach. After exploring extensive modifications throughout the parent structure, we arrived at a more highly M-1-selective antagonist, compound 13I (VU0415248). Muscarinic subtype selectivity across all five human and rat receptors for 13I, along with rat selectivity for the lead compound (ML012), is presented. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Melancon, Bruce J.; Bridges, Thomas M.; Utley, Thomas J.; Sheffler, Douglas J.; Noetzel, Meredith J.; Morrison, Ryan D.; Daniels, J. Scott; Niswender, Colleen M.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Wood, Michael R.] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. [Melancon, Bruce J.; Lamers, Alexander P.; Sulikowski, Gary A.; Lindsley, Craig W.; Wood, Michael R.] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA. [Melancon, Bruce J.; Bridges, Thomas M.; Utley, Thomas J.; Sheffler, Douglas J.; Noetzel, Meredith J.; Morrison, Ryan D.; Daniels, J. Scott; Niswender, Colleen M.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Wood, Michael R.] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA. [Melancon, Bruce J.; Lamers, Alexander P.; Bridges, Thomas M.; Sulikowski, Gary A.; Utley, Thomas J.; Noetzel, Meredith J.; Morrison, Ryan D.; Daniels, J. Scott; Niswender, Colleen M.; Jones, Carrie K.; Conn, P. Jeffrey; Lindsley, Craig W.; Wood, Michael R.] Vanderbilt Specialized Chem Ctr Probe Dev MLPCN, Nashville, TN 37232 USA. [Jones, Carrie K.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN 37232 USA. RP Wood, MR (reprint author), Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. EM michael.r.wood@vanderbilt.edu RI Conn, Peter/D-7848-2012 FU Seaside Therapeutics; NIMH [RO1MH082867]; NIH [U54MH084659]; NINDS [P50NS071669] FX The authors thank Seaside Therapeutics, NIMH (RO1MH082867), NIH (U54MH084659) and NINDS (P50NS071669) for support of our Program in the development of subtype selective mAChR antagonists. NR 18 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 15 PY 2012 VL 22 IS 2 BP 1044 EP 1048 DI 10.1016/j.bmcl.2011.11.110 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 883RY UT WOS:000299653500056 PM 22197142 ER PT J AU Coglianese, EE Qureshi, MM Vasan, RS Wang, TJ Moore, LL AF Coglianese, Erin E. Qureshi, Muhammad M. Vasan, Ramachandran S. Wang, Thomas J. Moore, Lynn L. TI Usefulness of the Blood Hematocrit Level to Predict Development of Heart Failure in a Community SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FOLLOW-UP; FRAMINGHAM; DISEASE; RISK; ERYTHROPOIETIN; PROGRAM; ANEMIA AB Current data suggest that increases in hemoglobin may decrease nitric oxide and adversely affect vascular function. In the preclinical setting, these changes could precipitate the development of heart failure (HF). We hypothesized that higher hematocrit (HCT) would be associated with an increased incidence of new-onset HF in the community. We evaluated 3,523 participants (59% women) from the Framingham Heart Study who were 50 to 65 years old and free of HF. Participants were followed prospectively until an HF event, death, or the end of 20 years of follow up. HCT was subdivided into 4 gender-specific categories (women: HCT 36.0 to 40.0, 40.1 to 42.0, 42.1 to 45.0, >45.0; men: 39.0 to 44.0, 44.1 to 45.0, 45.1 to 49.0, >49.0). Gender-pooled multivariable Cox proportional hazards models were used to estimate the association of HCT with incident HF, adjusting for clinical risk factors. During the follow-up period (61,417 person-years), 217 participants developed HF (100 events in women). There was a linear increase in risk of HF across the 4 HCT categories (p for trend = 0.002). Hazards ratios for HF in the low-normal, normal, and high HCT categories were 1.27 (95% confidence interval 0.82 to 1.97), 1.47 (1.01 to 2.15), and 1.78 (1.15 to 2.75), respectively, compared to the lowest HCT category (p for trend <0.0001). Adjustment for interim development of other cardiovascular diseases and restriction of the sample to nonsmokers did not alter the results. In conclusion, higher levels of HCT, even within the normal range, were associated with an increased risk of developing HF in this long-term follow-up study. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:241-245) C1 [Coglianese, Erin E.; Qureshi, Muhammad M.; Vasan, Ramachandran S.; Wang, Thomas J.; Moore, Lynn L.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Coglianese, Erin E.] Loyola Univ Hlth Syst, Div Cardiol, Maywood, IL USA. [Qureshi, Muhammad M.; Vasan, Ramachandran S.; Moore, Lynn L.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Qureshi, Muhammad M.; Vasan, Ramachandran S.; Moore, Lynn L.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Wang, Thomas J.; Moore, Lynn L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Moore, LL (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. EM llmoore@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [N01-HC-25195]; National Institutes of Health, Bethesda [RO1-HL-086875] FX This work was supported by Grant N01-HC-25195 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland and Grant RO1-HL-086875 from the National Institutes of Health, Bethesda (Dr. Wang). This work was completed during Dr. Cog Hawse's tenure as a Research Fellow of the Heart Failure Society of America. NR 19 TC 11 Z9 11 U1 1 U2 4 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 JAN 15 PY 2012 VL 109 IS 2 BP 241 EP 245 DI 10.1016/j.amjcard.2011.08.037 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 881NG UT WOS:000299492800017 PM 21996141 ER PT J AU Parker, BA Augeri, AL Capizzi, JA Ballard, KD Troyanos, C Baggish, AL D'Hemecourt, PA Thompson, PD AF Parker, Beth A. Augeri, Amanda L. Capizzi, Jeffrey A. Ballard, Kevin D. Troyanos, Christopher Baggish, Aaron L. D'Hemecourt, Pierre A. Thompson, Paul D. TI Effect of Statins on Creatine Kinase Levels Before and After a Marathon Run SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SKELETAL-MUSCLE; REDUCTASE INHIBITORS; GENE-EXPRESSION; EXERCISE; LOVASTATIN; RUNNERS; INCREASES; MARKERS; INJURY AB We measured the serum levels of myoglobin, total creatine kinase (CK), and the CK myocardial (CK-MB), muscle (CK-MM), and brain (CK-BB) isoenzymes in 37 subjects treated with statins and 43 nonstatin-treated controls running the 2011 Boston Marathon. Venous blood samples were obtained the day before (PRE) and within 1 hour (FINISH) and 24 hours after (POST) the race. The hematocrit and hemoglobin values were used to adjust for changes in the plasma volume. The CK distribution was normalized using log transformation before analysis. The exercise-related increase in CK 24 hours after exercise, adjusted for changes in plasma volume, was greater in the statin users (PRE to POST 133 +/- 15 to 1,104 +/- 150 U/L) than in the controls (PRE to POST 125 +/- 12 to 813 +/- 137 U/L; p = 0.03 for comparison). The increase in CK-MB 24 hours after exercise was also greater in the statin users (PRE to POST 1.1 +/- 3.9 to 8.9 +/- 7.0 U/L) than in the controls (PRE to POST 0.0 +/- 0.0 to 4.2 +/- 5.0 U/L; p <0.05 for comparison). However, the increases in muscle myoglobin did not differ at any point between the 2 groups. Increases in CK at both FINISH and POST race measurements were directly related to age in the statin users (r(2) = 0.13 and r(2) = 0.14, respectively; p <0.05) but not in the controls (r(2) = 0.02 and r(2) = 0.00, respectively; p >0.42), suggesting that susceptibility to exercise-induced muscle injury with statins increases with age. In conclusion, our results show that statins increase exercise-related muscle injury. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:282-287) C1 [Parker, Beth A.; Augeri, Amanda L.; Capizzi, Jeffrey A.; Thompson, Paul D.] Hartford Hosp, Dept Cardiol, Henry Low Heart Ctr, Hartford, CT 06115 USA. [Ballard, Kevin D.] Univ Connecticut, Dept Kinesiol, Storrs, CT USA. [Troyanos, Christopher; D'Hemecourt, Pierre A.] Childrens Hosp, Boston, MA 02115 USA. [Baggish, Aaron L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Parker, BA (reprint author), Hartford Hosp, Dept Cardiol, Henry Low Heart Ctr, Hartford, CT 06115 USA. EM bparker03@harthosp.org OI Ballard, Kevin/0000-0001-7587-1220 FU Hartford Hospital (Hartford, Connecticut) FX This study was funded by a research grant from Hartford Hospital (Hartford, Connecticut). NR 30 TC 33 Z9 33 U1 2 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2012 VL 109 IS 2 BP 282 EP 287 DI 10.1016/j.amjcard.2011.08.045 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 881NG UT WOS:000299492800024 PM 22036108 ER PT J AU Lancioni, C Nyendak, M Kiguli, S Zalwango, S Mori, T Mayanja-Kizza, H Balyejusa, S Null, M Baseke, J Mulindwa, D Byrd, L Swarbrick, G Scott, C Johnson, DF Malone, L Mudido-Musoke, P Boom, WH Lewinsohn, DM Lewinsohn, DA AF Lancioni, Christina Nyendak, Melissa Kiguli, Sarah Zalwango, Sarah Mori, Tomi Mayanja-Kizza, Harriet Balyejusa, Stephen Null, Megan Baseke, Joy Mulindwa, Deo Byrd, Laura Swarbrick, Gwendolyn Scott, Christine Johnson, Denise F. Malone, LaShaunda Mudido-Musoke, Philipa Boom, W. Henry Lewinsohn, David M. Lewinsohn, Deborah A. CA TB Res Unit TI CD8(+) T Cells Provide an Immunologic Signature of Tuberculosis in Young Children SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE Mycobacterium tuberculosis; infant; child; CD8-positive T lymphocytes; enzyme-linked immunosorbent spot ID CHILDHOOD PULMONARY TUBERCULOSIS; CALMETTE-GUERIN VACCINATION; GAMMA RELEASE ASSAYS; PRE-CHEMOTHERAPY ERA; MYCOBACTERIUM-TUBERCULOSIS; INTRATHORACIC TUBERCULOSIS; HOUSEHOLD CONTACTS; HIV-1 INFECTION; INDUCED SPUTUM; SKIN-TEST AB Rationale: The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis-specific CD8(+) T cells are generated in response to high bacillary loads occurring during tuberculosis. Objectives: To determine if M. tuberculosis-specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis. Methods: Enzyme-linked immunosorbent spot assays were used to measure IFN-gamma production in response to M. tuberculosis-specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8(+) T cells isolated from Ugandan children hospitalized with tuberculosis (n = 96) or healthy tuberculosis contacts (n = 62). Measurements and Main Results: The proportion of positive CD8(+) T-cell assays and magnitude of CD8(+) T-cell responses were significantly greater among young (<5 yr) tuberculosis cases compared with young contacts (P = 0.02, Fisher exact test, P = 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis-specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups. Conclusions: Among young children, M. tuberculosis-specific CD8(+) T cells develop in response to high bacillary loads, as occurs during tuberculosis, and are unlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-gamma-producing M. tuberculosis-specific CD8(+) T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease. C1 [Lancioni, Christina] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. [Lancioni, Christina; Zalwango, Sarah; Mayanja-Kizza, Harriet; Baseke, Joy; Mulindwa, Deo; Scott, Christine; Johnson, Denise F.; Malone, LaShaunda; Boom, W. Henry; Lewinsohn, David M.; Lewinsohn, Deborah A.] Case Western Reserve Univ, TB Res Unit, Cleveland, OH 44106 USA. [Nyendak, Melissa] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Mori, Tomi] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Null, Megan; Byrd, Laura; Lewinsohn, Deborah A.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA. [Kiguli, Sarah; Balyejusa, Stephen; Mudido-Musoke, Philipa] Makerere Univ, Coll Hlth Sci, Dept Pediat, Kampala, Uganda. [Mayanja-Kizza, Harriet] Makerere Univ, Coll Hlth Sci, Dept Med, Kampala, Uganda. [Zalwango, Sarah; Mayanja-Kizza, Harriet; Baseke, Joy; Mulindwa, Deo; Boom, W. Henry] Uganda CWRU Res Collaborat, Kampala, Uganda. [Swarbrick, Gwendolyn; Lewinsohn, David M.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland VA Med Ctr, Portland, OR 97201 USA. RP Lancioni, C (reprint author), CDRC P, OHSU, Dept Pediat, 707 SW Gaines St, Portland, OR 97239 USA. EM lancioni@ohsu.edu RI Yankovyi, Oleksandr/C-2020-2015; Piskunov, Roman/N-1772-2015; Vinnikova, Lydmila/P-5860-2015; Salnikov, Sergey/F-5727-2010; Petrov, Vladimir/K-6193-2015; Doroshenko, Alexander/N-7175-2015; Asach, Aleksei/N-2968-2016; Вардеванян, Вардан/S-8597-2016; Lewinsohn, David/I-4936-2013 OI Yankovyi, Oleksandr/0000-0003-2413-855X; Piskunov, Roman/0000-0001-6133-9233; Vinnikova, Lydmila/0000-0002-6106-1785; Salnikov, Sergey/0000-0001-7952-4496; Petrov, Vladimir/0000-0002-7733-1030; Doroshenko, Alexander/0000-0003-3693-3876; Asach, Aleksei/0000-0001-9509-2048; Вардеванян, Вардан/0000-0002-3642-6164; Mayanja-Kizza, Harriet/0000-0002-9297-6208; Lewinsohn, David/0000-0001-9906-9494 FU Tuberculosis Research Unit (TBRU); NIH [AI079847, HHSN266200400081C/NO1-A1-400081, AI48090, AI054474]; National Center For Research Resources [KL2RR024141]; VA Merit Review Grant; Portland VA Medical Center; ALA; Rainbow Babies and Children's Hospital; US NIAID [HHSN266200700022C/N01-AI-70022]; Uganda National Tuberculosis and Leprosy Program FX Supported in part by the Tuberculosis Research Unit (TBRU), established with Federal funds from US NIAID, under contract HHSN266200700022C/N01-AI-70022. This work was also supported by the following agencies and institutes: NIH grants AI079847, HHSN266200400081C/NO1-A1-400081, AI48090, and AI054474; The National Center For Research Resources KL2RR024141; VA Merit Review Grant and the Portland VA Medical Center; ALA Career Investigator Award; and the Rainbow Babies and Children's Hospital Fellowship Research Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; The authors acknowledge the invaluable contribution made by the study medical officers, health visitors, and laboratory and data personnel: Dr. Lorna Nshuti, Dr. Roy Mugerwa, Dr. Christina Hirsch, Allan Chiunda, Brenda Okware, Mark Breda, Dennis Dobbs, Hussein Kisingo, Albert Muganda, Richard Bamuhimbisa, Yusuf Mulumba, Deborah Nsamba, Barbara Kyeyune, Faith Kintu, Mary Nsereko, Gladys Mpalanyi, Janet Mukose, Grace Tumusiime, Pierre Peters, Alphonse Okwera, Keith Chervenak, Karen Morgan, Moses Joloba, Alfred Etwom, Micheal Angel Mugerwa, and Lisa Kucharski. They also acknowledge and thank Dr. Francis Adatu Engwau, Head of the Uganda National Tuberculosis and Leprosy Program, for his support of this project. They acknowledge the medical officers, nurses, and counselors at the National Tuberculosis Treatment Centre, Mulago Hospital, the Ugandan National Tuberculosis and Leprosy Program, and the Uganda Tuberculosis Investigation Bacteriological Unit, Wandegeya, for their contributions to this study. This study would not be possible without the generous participation of the Ugandan patients and families. Finally, they acknowledge Dr. Shannon McWeeney for advice on statistical methods. NR 49 TC 21 Z9 21 U1 1 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2012 VL 185 IS 2 BP 206 EP 212 DI 10.1164/rccm.201107-1355OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 879EC UT WOS:000299311500014 PM 22071329 ER PT J AU Bellani, G Pesenti, A Musch, G AF Bellani, Giacomo Pesenti, Antonio Musch, Guido TI Regional Lung Strain and Inflammation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter C1 [Bellani, Giacomo; Pesenti, Antonio] Univ Milano Bicocca, Monza, Italy. [Bellani, Giacomo; Pesenti, Antonio] San Gerardo Hosp, Monza, Italy. [Musch, Guido] Harvard Univ, Sch Med, Boston, MA USA. [Musch, Guido] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bellani, G (reprint author), Univ Milano Bicocca, Monza, Italy. RI Bellani, Giacomo/D-2379-2010; Pesenti, Antonio/H-7483-2012 OI Bellani, Giacomo/0000-0002-3089-205X; NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2012 VL 185 IS 2 BP 229 EP 230 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 879EC UT WOS:000299311500022 ER PT J AU Zhou, L Kawate, T Liu, XR Kim, YB Zhao, YJ Feng, GH Banerji, J Nash, H Whitehurst, C Jindal, S Siddiqui, A Seed, B Wolfe, JL AF Zhou, Li Kawate, Tomohiko Liu, Xiaorong Kim, Young Bae Zhao, Yajuan Feng, Guohong Banerji, Julian Nash, Huw Whitehurst, Charles Jindal, Satish Siddiqui, Arshad Seed, Brian Wolfe, Jia L. TI STAT6 phosphorylation inhibitors block eotaxin-3 secretion in bronchial epithelial cells SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Signal transducers and activators of transcription 6; Allergic inflammatory disease; STAT6 binder; STAT6 inhibitor; Eotaxin-3 ID SELECTION-MASS SPECTROMETRY; SIGNAL TRANSDUCER; AIRWAY HYPERRESPONSIVENESS; GENE-EXPRESSION; ACTIVATION; INTERLEUKIN-13; DIMERIZATION; PEPTIDE; DISEASE; HYPERREACTIVITY AB The STAT6 (signal transducer and activator of transcription 6) protein facilitates T-helper cell 2 (Th2) mediated responses that control IgE-mediated atopic diseases such as asthma. We have identified compounds that bind to STAT6 and inhibit STAT6 tyrosine phosphorylation induced by IL-4. In the bronchial epithelial cell line BEAS-2B, compound (R)-84 inhibits the secretion of eotaxin-3, a chemokine eliciting eosinophil infiltration. (R)-84 appears to prevent STAT6 from assuming the active dimer configuration by directly binding the protein and inhibiting tyrosine phosphorylation. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Zhou, Li; Kawate, Tomohiko; Liu, Xiaorong; Kim, Young Bae; Zhao, Yajuan; Feng, Guohong; Banerji, Julian; Seed, Brian; Wolfe, Jia L.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Nash, Huw; Whitehurst, Charles; Jindal, Satish; Siddiqui, Arshad] Neogenesis, Cambridge, MA 02139 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM bseed@ccib.mgh.harvard.edu NR 36 TC 10 Z9 10 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 15 PY 2012 VL 20 IS 2 SI SI BP 750 EP 758 DI 10.1016/j.bmc.2011.12.006 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 881ON UT WOS:000299496100025 PM 22217933 ER PT J AU Zhang, W Benmohamed, R Arvanites, AC Morimoto, RI Ferrante, RJ Kirsch, DR Silverman, RB AF Zhang, Wei Benmohamed, Radhia Arvanites, Anthony C. Morimoto, Richard I. Ferrante, Robert J. Kirsch, Donald R. Silverman, Richard B. TI Cyclohexane 1,3-diones and their inhibition of mutant SOD1-dependent protein aggregation and toxicity in PC12 cells SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Cyclohexane-1,3-dione; Amyotrophic lateral sclerosis; Mutant G93A SOD1; Blood-brain barrier penetration ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DEGENERATION; MOUSE MODEL; MICE; ALS AB Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Currently, there is only one FDA-approved treatment for ALS (riluzole), and that drug only extends life, on average, by 2-3 months. Mutations in Cu/Zn superoxide dismutase (SOD1) are found in familial forms of the disease and have played an important role in the study of ALS pathophysiology. On the basis of their activity in a PC12-G93A-YFP high-throughput screening assay, several bioactive compounds have been identified and classified as cyclohexane-1,3-dione (CHD) derivatives. A concise and efficient synthetic route has been developed to provide diverse CHD analogs. The structural modification of the CHD scaffold led to the discovery of a more potent analog (26) with an EC(50) of 700 nM having good pharmacokinetic properties, such as high solubility, low human and mouse metabolic potential, and relatively good plasma stability. It was also found to efficiently penetrate the blood-brain barrier. However, compound 26 did not exhibit any significant life span extension in the ALS mouse model. It was found that, although 26 was active in PC12 cells, it had poor activity in other cell types, including primary cortical neurons, indicating that it can penetrate into the brain, but is not active in neuronal cells, potentially due to poor selective cell penetration. Further structural modification of the CHD scaffold was aimed at improving global cell activity as well as maintaining potency. Two new analogs (71 and 73) were synthesized, which had significantly enhanced cortical neuronal cell permeability, as well as similar potency to that of 26 in the PC12-G93A assay. These CHD analogs are being investigated further as novel therapeutic candidates for ALS. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Zhang, Wei; Silverman, Richard B.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA. [Benmohamed, Radhia; Arvanites, Anthony C.; Kirsch, Donald R.] Cambria Pharmaceut, Cambridge, MA 02142 USA. [Morimoto, Richard I.] Northwestern Univ, Rice Inst Biomed Res, Dept Mol Biosci, Evanston, IL 60208 USA. [Ferrante, Robert J.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA. [Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA. [Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Ferrante, Robert J.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr GR H 00, Pittsburgh, PA 15206 USA. [Silverman, Richard B.] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chem Life Proc Inst, Dept Mol Biosci, Evanston, IL 60208 USA. RP Silverman, RB (reprint author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA. EM Agman@chem.northwestern.edu FU National Institutes of Health [1R43NS057849]; ALS Association; Department of Defense [AL093052]; Veterans Administration Pittsburgh Healthcare System, Highland Drive, Pittsburgh, PA FX We thank the National Institutes of Health [1R43NS057849], the ALS Association (TREAT program), the Department of Defense [AL093052], and the Veterans Administration Pittsburgh Healthcare System, 7180 Highland Drive, Pittsburgh, PA for their generous support of the research project. The authors are grateful to Biogen Idec, Inc. for carrying out the in vivo rat PK profiling tests, in vitro P450 reversible inhibition study, the plasma binding affinity assay, the hERG inhibition assay, and for funding to MDS Pharma Service (now Ricerca Biosciences, LLC), who carried out the LeadProfilingScreen of 26. NR 15 TC 8 Z9 8 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 15 PY 2012 VL 20 IS 2 SI SI BP 1029 EP 1045 DI 10.1016/j.bmc.2011.11.039 PG 17 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 881ON UT WOS:000299496100056 PM 22189273 ER PT J AU Macfarlane, R Heng, DYC Xie, WL Knox, JJ McDermott, DF Rini, BI Kollmannsberger, C Choueiri, TK AF Macfarlane, Robyn Heng, Daniel Y. C. Xie, Wanling Knox, Jennifer J. McDermott, David F. Rini, Brian I. Kollmannsberger, Christian Choueiri, Toni K. TI The impact of kidney function on the outcome of metastatic renal cell carcinoma patients treated with vascular endothelial growth factor-targeted therapy SO CANCER LA English DT Article DE metastatic renal cell carcinoma; sunitinib; bevacizumab; sorafenib; renal function; glomerular filtration rate ID GLOMERULAR-FILTRATION-RATE; INTERFERON-ALPHA; SUNITINIB; PHARMACOKINETICS; HEMODIALYSIS; SORAFENIB; CANCER AB BACKGROUND: A study was undertaken to investigate the effect of baseline renal function on treatment outcome in patients treated with vascular endothelial growth factor (VEGF)-targeted therapy for metastatic renal cell carcinoma (mRCC). METHODS: Retrospective data from 6 North American cancer centers (3 US and 3 Canadian) were pooled to identify patients with mRCC treated with VEGF-targeted therapy. Patient characteristics, response rate, time to treatment failure, and overall survival were collected. The Modification of Diet in Renal Disease formula was used at therapy initiation for calculation of glomerular filtration rate (GFR). RESULTS: Five hundred twenty-nine patients with mRCC who received sunitinib (n=323), sorafenib (n=165), or bevacizumab (n=41) were included in this analysis. Patient characteristics included: 74% male, median age 61 years, and median GFR 60.1 mL/min/1.73 m(2) (range, 6.5-174.2). On univariate analysis, patients with a GFR < 60 (n=262) were more likely to have had a previous nephrectomy (P <.0001) and to be older (P <.0001), but were less likely to have poor prognostic features such as anemia (P.041), hypercalcemia (P.008), neutrophilia (P=.039), thrombocytosis (P <. 0001), short diagnosis to treatment interval (P.007), and low Karnofsky performance status (P=.051). GFR < 60, when adjusted for poor risk factors, did not have an impact on type of objective response (odds ratio, 1.31; 95% confidence interval [ CI], 0.74-2.32; P.359), time to treatment failure (hazard ratio [HR], 0.97; 95% CI, 0.79-1.19; P=.772), or overall survival (HR, 0.90; 95% CI, 0.69-1.17; P.439). CONCLUSIONS: Renal function at therapy initiation does not adversely affect the efficacy of VEGF-targeted therapy in mRCC. Clinicians should not avoid treating patients with impaired baseline renal function. Cancer 2012; 118: 365-70. (C) 2011 American Cancer Society. C1 [Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB T2N 4N2, Canada. [Macfarlane, Robyn; Kollmannsberger, Christian] British Columbia Canc Agcy, Vancouver Canc Ctr, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Xie, Wanling] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Knox, Jennifer J.] Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M4X 1K9, Canada. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Rini, Brian I.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Heng, DYC (reprint author), Univ Calgary, Tom Baker Canc Ctr, 1331 29th St NW, Calgary, AB T2N 4N2, Canada. EM daniel.heng@albertahealthservices.ca NR 20 TC 8 Z9 8 U1 0 U2 1 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 JAN 15 PY 2012 VL 118 IS 2 BP 365 EP 370 DI 10.1002/cncr.26201 PG 6 WC Oncology SC Oncology GA 872YE UT WOS:000298846600012 PM 21717427 ER PT J AU Sorensen, AG Emblem, KE Polaskova, P Jennings, D Kim, H Ancukiewicz, M Wang, MY Wen, PY Ivy, P Batchelor, TT Jain, RK AF Sorensen, A. Gregory Emblem, Kyrre E. Polaskova, Pavlina Jennings, Dominique Kim, Heisoog Ancukiewicz, Marek Wang, Meiyun Wen, Patrick Y. Ivy, Percy Batchelor, Tracy T. Jain, Rakesh K. TI Increased Survival of Glioblastoma Patients Who Respond to Antiangiogenic Therapy with Elevated Blood Perfusion SO CANCER RESEARCH LA English DT Article ID VASCULAR NORMALIZATION; RECURRENT GLIOBLASTOMA; TUMOR VASCULATURE; KINASE INHIBITOR; CEDIRANIB; CANCER; EDEMA; BEVACIZUMAB AB The abnormal vasculature of the tumor microenvironment supports progression and resistance to treatment. Judicious application of antiangiogenic therapy may normalize the structure and function of the tumor vasculature, promoting improved blood perfusion. However, direct clinical evidence is lacking for improvements in blood perfusion after antiangiogenic therapy. In this study, we used MRI to assess tumor blood perfusion in 30 recurrent glioblastoma patients who were undergoing treatment with cediranib, a pan-VEGF receptor tyrosine kinase inhibitor. Tumor blood perfusion increased durably for more than 1 month in 7 of 30 patients, in whom it was associated with longer survival. Together, our findings offer direct clinical evidence in support of the hypothesis that vascular normalization can increase tumor perfusion and help improve patient survival. Cancer Res; 72(2); 402-7. (C)2011 AACR. C1 [Sorensen, A. Gregory; Emblem, Kyrre E.; Polaskova, Pavlina; Jennings, Dominique; Kim, Heisoog; Wang, Meiyun] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Ancukiewicz, Marek; Batchelor, Tracy T.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA. [Batchelor, Tracy T.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. [Ivy, Percy] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Emblem, Kyrre E.] Oslo Univ Hosp, Intervent Ctr, Oslo, Norway. [Kim, Heisoog] MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. RP Emblem, KE (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM sorensen@nmr.mgh.harvard.edu; kyrre@nmr.mgh.harvard.edu RI Emblem, Kyrre/H-6691-2012 OI Emblem, Kyrre/0000-0002-6580-9519 FU NCI/NIH [R21CA117079, R01CA129371, K24CA125440]; NIH [S10RR023401, S10RR019307, S10RR019254, S10RR023043, S10RR021110, R01CA137254, 5R01NS060918, UL1 RR025758]; NCI [P01CA80124]; Saic-Frederick Inc. [26XS263]; Norwegian Research Council [191088/V50]; Harvard Catalyst grant [M01-RR-01066]; Merck; Sanofi-Aventis; Genentech; Novartis; Medimmune; AstraZeneca; Amgen; Vascular Biogenics; Genzyme; Millennium; Pfizer; Dyax; Roche FX This work was supported by NCI/NIH R21CA117079, R01CA129371, and K24CA125440 (T.T. Batchelor); NIH S10RR023401, S10RR019307, S10RR019254, S10RR023043, S10RR021110, R01CA137254, and 5R01NS060918 (A.A. Sorensen); NCI P01CA80124 (R.K. Jain); Saic-Frederick Inc. grant 26XS263 (T.T. Batchelor); Norwegian Research Council grant 191088/V50 (K.E. Emblem); Harvard Catalyst grant M01-RR-01066 (T.T. Batchelor, A.G. Sorensen, and R.K. Jain); and NIH Award UL1 RR025758 (T.T. Batchelor, A.G. Sorensen, and R.K. Jain).; P.Y. Wen received research support from Merck, Sanofi-Aventis, Genentech, Novartis, Medimmune, AstraZeneca, Amgen, Vascular Biogenics, and Genzyme; T.T. Batchelor received support from Millennium, AstraZeneca, and Pfizer; and R.K. Jain received support from Dyax, MedImmune, and Roche. No potential conflicts of interest were disclosed by other authors. NR 20 TC 118 Z9 122 U1 3 U2 18 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 JAN 15 PY 2012 VL 72 IS 2 BP 402 EP 407 DI 10.1158/0008-5472.CAN-11-2464 PG 6 WC Oncology SC Oncology GA 879HW UT WOS:000299321300004 PM 22127927 ER PT J AU Chaiswing, L Zhong, WX Liang, YL Jones, DP Oberley, TD AF Chaiswing, Luksana Zhong, Weixiong Liang, Yongliang Jones, Dean P. Oberley, Terry D. TI Regulation of prostate cancer cell invasion by modulation of extra- and intracellular redox balance SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Cysteine; Cystine; Prostate cancer; Invasion; Growth; Free radicals ID MATRIX METALLOPROTEINASES; HUMAN PLASMA; IN-VITRO; STATE; GLUTATHIONE; PROLIFERATION; EXPRESSION; OXIDATION; GROWTH; DAMAGE AB Recent metabolic profiles of human prostate cancer tissues showed a significant increase in cysteine (Cys) and a significant decrease in reduced glutathione (GSH) during cancer progression from low- to high-grade Gleason scores. Cys is primarily localized extracellularly, whereas GSH is present mostly inside the cell. We hypothesized that extra-or intracellular redox state alterations differentially regulate cell invasion in PO prostate carcinoma cells versus PrEC normal prostate epithelial cells. Cells were exposed to media with calculated Cys/CySS redox potentials (E(h)CySS) ranging from -60 to -180 mV. After 3 h exposure to a reducing extracellular redox state (E(h)CySS = -180 mV), matrix metalloprotease (MMP), gelatinase, and NADPH oxidase activities increased, correlating with increases in cell invasion, cell migration, and extracellular hydrogen peroxide levels in PO cells but not PrECs. Knockdown of NADPH oxidase or MMP with silencing RNAs during cultivation with E(h)CySS = -180 mV medium significantly decreased PO cell invasion. Modulation of extra- and intracellular redox states by exposure of PC3 cells to Cys/CySS-free medium (approx E(h)CySS = -87 mV) containing 500 mu M N-acetylcysteine resulted in a more reducing intracellular redox state and a significant decrease in cell invasive ability. The decrease in PC3 cell invasion induced by these conditions correlated with a decrease in MMP activity. Our studies demonstrated that an extracellular redox state that was more reducing than a physiologic microenvironment redox state increased PC3 cancer cell invasive ability, whereas an intracellular redox environmental that was more reducing than an intracellular physiologic redox state inhibited PC3 cell invasive ability. Published by Elsevier Inc. C1 [Chaiswing, Luksana; Zhong, Weixiong; Oberley, Terry D.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53706 USA. [Zhong, Weixiong; Oberley, Terry D.] William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. [Liang, Yongliang; Jones, Dean P.] Emory Univ, Dept Med, Div Pulm Allergy & Crit Care Med, Atlanta, GA 30322 USA. RP Oberley, TD (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53706 USA. EM toberley@wisc.edu FU University of Wisconsin; Department of Pathology Research and Development Committee; University of Wisconsin-Madison Graduate School; Society for Free Radical Biology Medicine; National Cancer Institute; University of Wisconsin Carbone Cancer Center [P30 CA014520]; NIH [RO1 CA07359902, RO1 CA09485301] FX The contents do not represent the views of the U.S. Department of Veterans Affairs. This work was supported in part by funds from the University of Wisconsin, Department of Pathology Research and Development Committee, University of Wisconsin-Madison Graduate School, a 2010 minifellowship award from the Society for Free Radical Biology & Medicine and from the National Cancer Institute, University of Wisconsin Carbone Cancer Center (NIH Grant P30 CA014520), NIH Grants RO1 CA07359902 and RO1 CA09485301 (T.D.O.; Co-I), and resources and facilities at the William S. Middleton Memorial Veterans Hospital (Madison, WI, USA). The authors thank Dr. Young-Mi Go, Department of Medicine, Emory University (Atlanta, GA), for technical training of the Trx1 redox Western blot technique. NR 32 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN 15 PY 2012 VL 52 IS 2 BP 452 EP 461 DI 10.1016/j.freeradbiomed.2011.10.489 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 878IB UT WOS:000299247600023 PM 22120495 ER PT J AU La Bonte, LR Pavlov, VI Tan, YS Takahashi, K Takahashi, M Banda, NK Zou, CH Fujita, T Stahl, GL AF La Bonte, Laura R. Pavlov, Vasile I. Tan, Ying S. Takahashi, Kazue Takahashi, Minoru Banda, Nirmal K. Zou, Chenhui Fujita, Teizo Stahl, Gregory L. TI Mannose-Binding Lectin-Associated Serine Protease-1 Is a Significant Contributor to Coagulation in a Murine Model of Occlusive Thrombosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; COMPLEMENT-PATHWAY; REPERFUSION INJURY; OXIDATIVE STRESS; MYOCARDIAL-INFARCTION; PLATELET-AGGREGATION; VASCULAR THROMBOSIS; ARTERIAL THROMBOSIS; ENDOTHELIAL-CELLS; PROTEIN-C AB Bleeding disorders and thrombotic complications constitute a major cause of death and disability worldwide. Although it is known that the complement and coagulation systems interact, no studies have investigated the specific role or mechanisms of lectin-mediated coagulation in vivo. FeCl(3) treatment resulted in intra-arterial occlusive thrombogenesis within 10 min in wild-type (WT) and C2/factor B-null mice. In contrast, mannose-binding lectin (MBL)-null and MBL-associated serine protease (MASP)-1/-3 knockout (KO) mice had significantly decreased FeCl(3)-induced thrombogenesis. Reconstitution with recombinant human (rh) MBL restored FeCl3-induced thrombogenesis in MBL-null mice to levels comparable to WT mice, suggesting a significant role of the MBL/MASP complex for in vivo coagulation. Additionally, whole blood aggregation demonstrated increased MBL/MASP complex-dependent platelet aggregation. In vitro, MBL/MASP complexes were captured on mannan-coated plates, and cleavage of a chromogenic thrombin substrate (S2238) was measured. We observed no significant differences in S2238 cleavage between WT, C2/factor B-null, MBL-A(-/-), or MBL-C(-/-) sera; however, MBL-null or MASP-1/-3 KO mouse sera demonstrated significantly decreased S2238 cleavage. rhMBL alone failed to cleave S2238, but cleavage was restored when rMASP-1 was added to either MASP-1/-3 KO sera or rhMBL. Taken together, these findings indicate that MBL/MASP complexes, and specifically MASP-1, play a key role in thrombus formation in vitro and in vivo. The Journal of Immunology, 2012, 188: 885-891. C1 [La Bonte, Laura R.; Pavlov, Vasile I.; Tan, Ying S.; Zou, Chenhui; Stahl, Gregory L.] Harvard Univ, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Brigham & Womens Hosp,Harvard Inst Med,Sch Med, Boston, MA 02115 USA. [Takahashi, Kazue] Massachusetts Gen Hosp, Dept Pediat, Dev Immunol Program, Boston, MA 02139 USA. [Takahashi, Minoru; Fujita, Teizo] Fukushima Med Univ, Sch Med, Dept Immunol, Fukushima 9601295, Japan. [Banda, Nirmal K.] Univ Colorado, Dept Med, Aurora, CO 80045 USA. RP Stahl, GL (reprint author), Harvard Univ, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Brigham & Womens Hosp,Harvard Inst Med,Sch Med, HIM 845A,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM gstahl@zeus.bwh.harvard.edu FU National Institutes of Health [HL056086, HL099130, AI089781]; Ruth L. Kirschstein National Research Service [HL099043] FX This work was supported in part by National Institutes of Health Grants HL056086, HL099130, and AI089781. L.R.L.B. is funded by Ruth L. Kirschstein National Research Service Award Fellowship HL099043. NR 55 TC 34 Z9 34 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2012 VL 188 IS 2 BP 885 EP 891 DI 10.4049/jimmunol.1102916 PG 7 WC Immunology SC Immunology GA 879IU UT WOS:000299323700043 PM 22156595 ER PT J AU Smith, MA Schnellmann, RG AF Smith, Matthew A. Schnellmann, Rick G. TI Mitochondrial calpain 10 is degraded by Lon protease after oxidant injury SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Calpain 10; Lon; Renal proximal tubular cells; Degradation; Toxicant; Inhibitors ID PROXIMAL TUBULE CELLS; OXIDATIVE STRESS; QUALITY CONTROL; RENAL-CELLS; INHIBITION; ACTIVATION; DEGRADATION; EXPRESSION; LOCALIZATION; CLEAVAGE AB Calpain 10 is ubiquitously expressed and is one of four mitochondrial matrix proteases. We determined that over-expression or knock-down of mitochondrial calpain 10 results in cell death, demonstrating that mitochondrial calpain 10 is required for viability. Thus, we studied calpain 10 degradation in isolated mitochondrial matrix, mitochondria and in renal proximal tubular cells (RPTC) under control and toxic conditions. Using isolated renal cortical mitochondria and mitochondrial matrix, calpain 10 underwent rapid degradation at 37 degrees C that was blocked with Lon inhibitors but not by calpain or proteasome inhibitors. While exogenous Ca(2+) addition, Ca(2+) chelation or exogenous ATP addition had no effect on calpain 10 degradation, the oxidants tert-butyl hydroperoxide (TBHP) or H(2)O(2) increased the rate of degradation. Using RPTC, mitochondrial and cytosolic calpain 10 increased in the presence of MG132 (Lon/proteasome inhibitor) but only cytosolic calpain 10 increased in the presence of epoxomicin (proteasome inhibitor). Furthermore, TBHP and H(2)O(2) oxidized mitochondrial calpain 10, decreased mitochondrial, but not cytosolic calpain 10, and pretreatment with MG132 blocked TBHP-induced degradation of calpain 10. In summary, mitochondrial calpain 10 is selectively degraded by Lon protease under basal conditions and is enhanced under and oxidizing conditions, while cytosolic calpain 10 is degraded by the proteasome. Published by Elsevier Inc. C1 [Smith, Matthew A.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU NIH [GM 084147, C06 RR-015455]; NIH/NIEHS [T32ES012878-05]; Department of Veterans Affairs FX This study was supported by NIH Grant [GM 084147], the NIH/NIEHS Training Program in Environmental Stress Signaling [T32ES012878-05], and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. Animal facilities were funded by NIH grant [C06 RR-015455]. NR 43 TC 7 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 15 PY 2012 VL 517 IS 2 BP 144 EP 152 DI 10.1016/j.abb.2011.11.023 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 876ZJ UT WOS:000299146000008 PM 22179018 ER PT J AU Wamsley, EJ Tucker, MA Shinn, AK Ono, KE McKinley, SK Ely, AV Goff, DC Stickgold, R Manoach, DS AF Wamsley, Erin J. Tucker, Matthew A. Shinn, Ann K. Ono, Kim E. McKinley, Sophia K. Ely, Alice V. Goff, Donald C. Stickgold, Robert Manoach, Dara S. TI Reduced Sleep Spindles and Spindle Coherence in Schizophrenia: Mechanisms of Impaired Memory Consolidation? SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Memory consolidation; motor skill; procedural learning; schizophrenia; sleep; sleep spindles ID EYE-MOVEMENT SLEEP; SLOW-WAVE SLEEP; CORTICOTHALAMIC FEEDBACK; RETICULAR NUCLEUS; MOTOR SEQUENCE; NAIVE PATIENTS; EEG COHERENCE; RETENTION; NEURONS; ABNORMALITIES AB Background: Sleep spindles are thought to induce synaptic changes and thereby contribute to memory consolidation during sleep. Patients with schizophrenia show dramatic reductions of both spindles and sleep-dependent memory consolidation, which may be causally related. Methods: To examine the relations of sleep spindle activity to sleep-dependent consolidation of motor procedural memory, 21 chronic, medicated schizophrenia outpatients and 17 healthy volunteers underwent polysomnography on two consecutive nights. On the second night, participants were trained on the finger-tapping motor sequence task (MST) at bedtime and tested the following morning. The number, density, frequency, duration, amplitude, spectral content, and coherence of stage 2 sleep spindles were compared between groups and examined in relation to overnight changes in MST performance. Results: Patients failed to show overnight improvement on the MST and differed significantly from control participants who did improve. Patients also exhibited marked reductions in the density (reduced 38% relative to control participants), number (reduced 36%), and coherence (reduced 19%) of sleep spindles but showed no abnormalities in the morphology of individual spindles or of sleep architecture. In patients, reduced spindle number and density predicted less overnight improvement on the MST. In addition, reduced amplitude and sigma power of individual spindles correlated with greater severity of positive symptoms. Conclusions: The observed sleep spindle abnormalities implicate thalamocortical network dysfunction in schizophrenia. In addition, the findings suggest that abnormal spindle generation impairs sleep-dependent memory consolidation in schizophrenia, contributes to positive symptoms, and is a promising novel target for the treatment of cognitive deficits in schizophrenia. C1 [Wamsley, Erin J.; Tucker, Matthew A.; McKinley, Sophia K.; Ely, Alice V.; Stickgold, Robert] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. [Shinn, Ann K.] McLean Hosp, Psychot Disorders Div, Belmont, MA 02178 USA. [Ono, Kim E.; Goff, Donald C.; Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Manoach, Dara S.] Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp Charlestown Navy Yard, Dept Psychiat, 149 13th St,Room 1-111, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu FU Sunovion Pharmaceuticals, Inc. [30675]; National Institutes of Health [R01-MH48832, T32-HL07901]; National Center for Research Resources [UL1-RR025758, M01-RR-01066]; Harvard Clinical and Translational Science Center; Massachusetts General Hospital Clinical Research Center; Merck Company; Sepracor, Inc.; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology/Beth Israel Deaconess Medical Center; Pfizer, Inc.; Pfizer; Janssen; Novartis; GlaxoSmithKline FX This work was funded by research Grant #30675 from Sunovion Pharmaceuticals, Inc. (formerly Sepracor, Inc.), to DSM; the National Institutes of Health R01-MH48832 and T32-HL07901; and the National Center for Research Resources UL1-RR025758 and M01-RR-01066, Harvard Clinical and Translational Science Center.; We are grateful to the staff of the Massachusetts General Hospital Clinical Research Center, particularly Mary Sullivan, R.N., for their support and to Michael Halassa, M. D., Ph.D., for his comments on the manuscript.; RS consults to Actelion Pharmaceuticals, has received speaking honoraria from Eli Lilly, and has received research support from Merck & Company. DSM has received a consulting fee from Sepracor, Inc., and a speaking honorarium from Eli Lilly. AKS is supported, in part, by an unrestricted educational Grant from the Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology/Beth Israel Deaconess Medical Center, in collaboration with Merck & Company and Pfizer, Inc. DCG reports having served as a consultant or advisor to Xytis, Forest Labs, Pfizer, Indevus Pharmaceuticals, H. Lundbeck, Schering-Plough, Eli Lilly, Takeda, Biovail, Solvay, Hoffman- La Roche, Cypress, and Dianippon Sumitomo. He served on a Data and Safety Monitoring Board for Otsuka and Wyeth. He received research funding from Pfizer, Janssen, Novartis, and GlaxoSmithKline. All other authors report no biomedical financial interests or potential conflicts of interest. NR 77 TC 104 Z9 106 U1 4 U2 24 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 JAN 15 PY 2012 VL 71 IS 2 BP 154 EP 161 DI 10.1016/j.biopsych.2011.08.008 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 863GH UT WOS:000298150300010 PM 21967958 ER PT J AU Ribas, A Hersey, P Middleton, MR Gogas, H Flaherty, KT Sondak, VK Kirkwood, JM AF Ribas, Antoni Hersey, Peter Middleton, Mark R. Gogas, Helen Flaherty, Keith T. Sondak, Vernon K. Kirkwood, John M. TI New Challenges in Endpoints for Drug Development in Advanced Melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID RANDOMIZED CLINICAL-TRIALS; METASTATIC MELANOMA; CTLA4 BLOCKADE; INHIBITION; RESISTANCE; BRAF; METAANALYSIS; SURVIVAL; THERAPY AB During the past 3 decades, the field of clinical research for the treatment of advanced melanoma lacked significant advances. Available drugs had low antitumor activity and no proven benefit in overall survival. Recently, new drugs developed based on an in-depth understanding of the biology of this disease have shown significant benefit, with ipilimumab and vemurafenib having recently shown a positive impact in overall survival in patients with metastatic melanoma leading to approval in this indication by the U. S. Food and Drug Administration. This rapid introduction of new active agents is likely to challenge current notions on how to develop future agents for the treatment of melanoma. The strong evidence of benefit for initial agents that modulate immune regulatory checkpoints or target driver oncogenes has spurred great interest in developing other similarly acting agents. However, this will pose problems in the choice of endpoints for the future definitive clinical trials, and the hurdles for achieving these endpoints will be higher given the similar activity for comparator agents or the availability of competing agents for salvage therapy. This new reality will likely require tailoring registrational clinical trial endpoints to the patient benefits shown in early clinical testing. In this perspective article, we illustrate the challenges in the choice of endpoints for registrational trials in metastatic melanoma and that, with an improved understanding of the agent being developed, the design of the registrational programs can be informed by earlier mechanistic studies to define the assumptions for definitive clinical testing. Clin Cancer Res; 18(2); 336-41. (C) 2011 AACR. C1 [Ribas, Antoni] Univ Calif Los Angeles, UCLA Med Ctr, Div Hematol Oncol, Dept Med, Los Angeles, CA 90095 USA. [Ribas, Antoni] UCLAs Jonsson Comprehens Canc Ctr, Los Angeles, CA USA. [Hersey, Peter] Univ Sydney, Melanoma Inst Australia, Sydney, NSW 2006, Australia. [Middleton, Mark R.] Univ Oxford, Churchill Hosp, Dept Oncol, Oxford, England. [Gogas, Helen] Univ Athens, Dept Med 1, Athens, Greece. [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Sondak, Vernon K.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Cutaneous Oncol, Tampa, FL 33682 USA. [Kirkwood, John M.] Univ Pittsburgh, Inst Canc, Melanoma & Skin Canc Program, Pittsburgh, PA USA. RP Ribas, A (reprint author), Univ Calif Los Angeles, UCLA Med Ctr, Div Hematol Oncol, Dept Med, 11-934 Factor Bldg,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM aribas@mednet.ucla.edu FU Seaver Institute; Caltech-UCLA Joint Center for Translational Research; Wesley Coyle Fund; Melanoma Research Alliance; Melanoma Research Foundation; Oxford NIHR Biomedical Research Centre; Cancer Research UK; UK Experimental Cancer Medicines Centre initiative; National Cancer Institute [P50CA121973, U10CA039229] FX A. Ribas is funded by The Seaver Institute, the Caltech-UCLA Joint Center for Translational Research, the Wesley Coyle Fund, the Melanoma Research Alliance, and the Melanoma Research Foundation. M.R. Middleton is supported by the Oxford NIHR Biomedical Research Centre, Cancer Research UK, and the UK Experimental Cancer Medicines Centre initiative. J.M. Kirkwood is supported by the National Cancer Institute awards P50CA121973 and U10CA039229. NR 24 TC 36 Z9 37 U1 0 U2 2 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 JAN 15 PY 2012 VL 18 IS 2 BP 336 EP 341 DI 10.1158/1078-0432.CCR-11-2323 PG 6 WC Oncology SC Oncology GA 879HR UT WOS:000299320800003 PM 22142824 ER PT J AU Reagan, MR Ghobrial, IM AF Reagan, Michaela R. Ghobrial, Irene M. TI Multiple Myeloma Mesenchymal Stem Cells: Characterization, Origin, and Tumor-Promoting Effects SO CLINICAL CANCER RESEARCH LA English DT Review ID MARROW STROMAL CELLS; MEDIATED DRUG-RESISTANCE; NF-KAPPA-B; HUMAN BONE-MARROW; IN-VIVO; INTERLEUKIN-6 SECRETION; CYTOKINE PRODUCTION; CAM-DR; EXPRESSION; ADHESION AB Hematologic malignancies rely heavily on support from host cells through a number of well-documented mechanisms. Host cells, specifically mesenchymal stem cells (MSC), support tumor cell growth, metastasis, survival, bone marrow colonization, and evasion of the immune system. In multiple myeloma, similar to solid tumors, supporting cells have typically been considered healthy host cells. However, recent evidence reveals that many MSCs derived from patients with multiple myeloma (MM-MSC) show significant defects compared with MSCs from nondiseased donors (ND-MSC). These abnormalities range from differences in gene and protein expression to allelic abnormalities and can initiate after less than 1 day of coculture with myeloma cells or persist for months, perhaps years, after removal from myeloma influence. Alterations in MM-MSC function contribute to disease progression and provide new therapeutic targets. However, before the scientific community can capitalize on the distinctions between MM-MSCs and ND-MSCs, a number of confusions must be clarified, as we have done in this review, including the origin(s) of MM-MSCs, identification and characterization of MM-MSCs, and downstream effects and feedback circuits that support cancer progression. Further advances require more genetic analysis of MM-MSCs and disease models that accurately represent MSC-MM cell interactions. Clin Cancer Res; 18(2); 342-9. (C) 2011 AACR. C1 [Reagan, Michaela R.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM irene_ghobrial@dfci.harvard.edu RI Reagan, Michaela/E-3549-2017; OI Reagan, Michaela/0000-0003-2884-6481 FU Millennium; Bristol-Myers Squibb; Noxxon; NIH [1R01CA133799, 1R01CA152607] FX M.R. Reagan declares no competing financial interests. I.M. Ghobrial received research funding from Millennium, Bristol-Myers Squibb, and Noxxon and is on the advisory board or consultant for Millennium, Celgene, Novartis, Bristol-Myers Squibb, Noxxon, and Polyphor.; Supported in part by NIH Grants 1R01CA133799 and 1R01CA152607 (I.M. Ghobrial). NR 66 TC 41 Z9 44 U1 1 U2 6 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 JAN 15 PY 2012 VL 18 IS 2 BP 342 EP 349 DI 10.1158/1078-0432.CCR-11-2212 PG 8 WC Oncology SC Oncology GA 879HR UT WOS:000299320800004 PM 22065077 ER PT J AU Yuen, HF Chan, KK Grills, C Murray, JT Platt-Higgins, A Eldin, OS O'Byrne, K Janne, P Fennell, DA Johnston, PG Rudland, PS El-Tanani, M AF Yuen, Hiu-Fung Chan, Ka-Kui Grills, Claire Murray, James T. Platt-Higgins, Angela Eldin, Osama Sharaf O'Byrne, Ken Janne, Pasi Fennell, Dean A. Johnston, Patrick G. Rudland, Philip S. El-Tanani, Mohamed TI Ran Is a Potential Therapeutic Target for Cancer Cells with Molecular Changes Associated with Activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK Pathways SO CLINICAL CANCER RESEARCH LA English DT Article ID NUCLEAR TRANSPORT; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; NUCLEOCYTOPLASMIC TRANSPORT; GENE SIGNATURE; BREAST-CANCER; ERK; SURVIVAL; PROTEIN; KINASE; AKT AB Purpose: Cancer cells have been shown to be more susceptible to Ran knockdown than normal cells. We nowinvestigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK [mitogen-activated protein/extracellular signal-regulated kinase (ERK; MEK)] and phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 activities. Experimental Design: Apoptosis was measured by flow cytometry [propidium iodide (PI) and Annexin V staining] and MTT assay in cancer cells grown under different conditions after knockdown of Ran. The correlations between Ran expression and patient survival were examined in breast and lung cancers. Results: Cancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. K-Ras-mutated, c-Met-amplified, and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c-Met or osteopontin expression, or with oncogenic mutations of K-Ras or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Conclusion: Ran is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. Clin Cancer Res; 18(2); 380-91. (C) 2011 AACR. C1 [Yuen, Hiu-Fung; Chan, Ka-Kui; Grills, Claire; Murray, James T.; Fennell, Dean A.; Johnston, Patrick G.; El-Tanani, Mohamed] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7BL, Antrim, North Ireland. [Platt-Higgins, Angela; Rudland, Philip S.] Univ Liverpool, Sch Biol Sci, Canc & Polio Res Fund Labs, Liverpool L69 3BX, Merseyside, England. [Eldin, Osama Sharaf] St Vincents Hosp, Dept Pathol, Dublin 4, Ireland. [O'Byrne, Ken] St James Hosp, Dublin 8, Ireland. [Janne, Pasi] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP El-Tanani, M (reprint author), Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7BL, Antrim, North Ireland. EM m.el-tanani@qub.ac.uk OI Murray, James/0000-0002-6928-2347 FU CRUK; Cancer and Polio Research Fund FX The authors thank CRUK for the postdoctoral fellowship to H.-F. Yuen.; This work was supported by Cancer and Polio Research Fund for funding the immunohistochemical studies on breast cancer. NR 47 TC 29 Z9 33 U1 0 U2 11 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 JAN 15 PY 2012 VL 18 IS 2 BP 380 EP 391 DI 10.1158/1078-0432.CCR-11-2035 PG 12 WC Oncology SC Oncology GA 879HR UT WOS:000299320800008 PM 22090358 ER PT J AU Schoenfeld, AJ Hornicek, FJ Pedlow, FX Kobayashi, W Raskin, KA Springfield, D DeLaney, TF Nielsen, GP Mankin, HJ Schwab, JH AF Schoenfeld, Andrew J. Hornicek, Francis J. Pedlow, Francis X. Kobayashi, Wendy Raskin, Kevin A. Springfield, Dempsey DeLaney, Thomas F. Nielsen, G. Petur Mankin, Henry J. Schwab, Joseph H. TI Chondrosarcoma of the Mobile Spine SO SPINE LA English DT Article DE chondrosarcoma; spine; en bloc resection; radiation; outcomes ID BONE; IRRADIATION; TUMORS AB Study Design. Retrospective case series. Objective. To determine the effect of modern surgical and aggressive radiation techniques on outcome in patients with spinal chondrosarcoma. Summary of Background Data. Chondrosarcoma of the spine presents a difficult surgical challenge. Surgical excision is considered the standard of care, yet complete excision is not always feasible, and rates of local control and survival are inferior to those reported for the extremities. Methods. We performed a retrospective review of cases of chondrosarcoma involving the spine above the sacrum treated surgically at our institution between 1984 and 2006. Medical charts, radiology reports, pathology reports, and operative notes were reviewed for all patients. Available imaging studies were also reviewed. The Student t test and Fisher exact test were used to compare baseline differences between groups. Survivorship analysis was performed using Kaplan-Meier methodology. Overall survival was calculated on the basis of en bloc resection, margins, local recurrence, and metastasis. Results. Twenty-one patients were treated surgically for chondrosarcoma of the mobile spine. Twenty of the 21 patients were also treated with radiation with a mean dose of 71 Gy (range, 53-83). The average overall survival for all patients in our series was 120.5 months (SE = 32.9; range, 8.5-298.9 months). The 1- and 5-year survival rates for all patients were 90% and 61%, respectively. Patients treated with en bloc resection had a better overall survival (198 months: SE = 24.5; range, 24-224.7 months) than those who underwent intralesional excision (77 months: SE = 27.3; range, 8.5-298.9 months) (P = 0.05). Five (24%) patients developed local recurrence and 9 (43%) developed metastasis. All recurrences occurred in patients who underwent intralesional resection. Metastasis, high-grade tumor, and positive surgical margins were associated with worse overall survival (P < 0.001, 0.02, and 0.04, respectively). Conclusion. In this series, en bloc resection, the absence of metastasis, low-grade tumors, and negative margins were associated with improved overall survival. The aggressive use of sophisticated surgical and radiation techniques appears to confer an advantage to patients, decreasing local recurrence and increasing overall survival, even following incomplete surgical resection. C1 [Schoenfeld, Andrew J.; Hornicek, Francis J.; Pedlow, Francis X.; Raskin, Kevin A.; Springfield, Dempsey; Mankin, Henry J.; Schwab, Joseph H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Kobayashi, Wendy; DeLaney, Thomas F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Nielsen, G. Petur] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Schwab, JH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. EM jhschwab@partners.org OI Schoenfeld, Andrew/0000-0002-3691-1215 NR 22 TC 8 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JAN 15 PY 2012 VL 37 IS 2 BP 119 EP 126 DI 10.1097/BRS.0b013e31823d2143 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 877FT UT WOS:000299163400016 PM 22037533 ER PT J AU Vitalo, AG Gorantla, S Fricchione, JG Scichilone, JM Camacho, J Niemi, SM Denninger, JW Benson, H Yarmush, ML Levine, JB AF Vitalo, Antonia G. Gorantla, Sasikanth Fricchione, Jonathan G. Scichilone, John M. Camacho, Jennifer Niemi, Steven M. Denninger, John W. Benson, Herbert Yarmush, Martin L. Levine, John B. TI Environmental enrichment with nesting material accelerates wound healing in isolation-reared rats SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE Environmental enrichment; Isolation rearing; Wound healing; Bedding; Nesting ID MEDIAL PREFRONTAL CORTEX; PROINFLAMMATORY CYTOKINE PRODUCTION; SOCIAL-ISOLATION SYNDROME; DEPRESSIVE-LIKE BEHAVIOR; EARLY GENE-EXPRESSION; VENTRAL STRIATUM; LABORATORY MICE; PREPULSE INHIBITION; SUCROSE CONSUMPTION; PHYSICAL ENRICHMENT AB Early enrichment (EE) programs provide a well-established approach to mitigate the deleterious effects of childhood adversity. To better understand the therapeutic features of EE, in the current study we compared the effect of two forms of nesting material on isolation reared (IR) rats. We found that both materials, absent of social and any other physical enrichment, significantly improved wound healing rates. The results suggest that this animal model may provide useful insights into the critical components of EE. (C) 2011 Elsevier B.V. All rights reserved. C1 [Yarmush, Martin L.] Shriners Burns Hosp, Ctr Engn & Med, Boson, MA 02114 USA. [Vitalo, Antonia G.; Gorantla, Sasikanth; Fricchione, Jonathan G.; Scichilone, John M.; Denninger, John W.; Levine, John B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Yarmush, Martin L.; Levine, John B.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Benson, Herbert] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Vitalo, Antonia G.; Gorantla, Sasikanth; Fricchione, Jonathan G.; Scichilone, John M.; Denninger, John W.; Benson, Herbert; Levine, John B.] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Vitalo, Antonia G.; Gorantla, Sasikanth; Fricchione, Jonathan G.; Scichilone, John M.; Yarmush, Martin L.; Levine, John B.] Massachusetts Gen Hosp, Ctr Engn & Med, Boston, MA 02114 USA. [Camacho, Jennifer; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Denninger, John W.; Levine, John B.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Yarmush, Martin L.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. [Benson, Herbert] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Niemi, Steven M.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Yarmush, ML (reprint author), Shriners Burns Hosp, Ctr Engn & Med, 51 Blossom St, Boson, MA 02114 USA. EM ireis@sbi.org; jblevine@partners.org FU John Henry Foundation; Benson-Henry Institute (BHI) for Mind Body Medicine at Massachusetts GeneralHospital; Shriners Burns Hospital for Children - Boston FX Funding for this study was provided by the John Henry Foundation, the Benson-Henry Institute (BHI) for Mind Body Medicine at Massachusetts GeneralHospital, and the Medical Research Programs of the Shriners Burns Hospital for Children - Boston. The John-Henry Foundation provides research funding to the BHI. One of the authors, Herbert Benson, MD, is Principal Investigator on the John Henry Foundation Fund at BHI. The John Henry Foundation itself had no role in study design, data collection, analysis, or decision to publish, or in preparation of the manuscript. The authors acknowledge the help of Mr. Don Poulsen in preparing the figures. NR 57 TC 4 Z9 4 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JAN 15 PY 2012 VL 226 IS 2 BP 606 EP 612 DI 10.1016/j.bbr.2011.09.038 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 871YW UT WOS:000298774600032 PM 22008380 ER PT J AU Lee, J Giordano, S Zhang, JH AF Lee, Jisun Giordano, Samantha Zhang, Jianhua TI Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling SO BIOCHEMICAL JOURNAL LA English DT Review DE autophagy; mitochondrion; neurodegeneration; nitrative stress; oxidative stress; redox signalling ID AMYOTROPHIC-LATERAL-SCLEROSIS; MANGANESE SUPEROXIDE-DISMUTASE; ANTIOXIDANT RESPONSIVE ELEMENTS; COMPLEX-I DEFICIENCY; LIPOFUSCINOSES BATTEN-DISEASE; CHAPERONE-MEDIATED AUTOPHAGY; PATHOGENIC DJ-1 MUTATIONS; MOTOR-NEURON DEGENERATION; HYPOXIA-INDUCED AUTOPHAGY; SMOOTH-MUSCLE-CELLS AB Reactive oxygen and nitrogen species change cellular responses through diverse mechanisms that are now being defined. At low levels, they are signalling molecules, and at high levels, they damage organelles, particularly the mitochondria. Oxidative damage and the associated mitochondrial dysfunction may result in energy depletion, accumulation of cytotoxic mediators and cell death. Understanding the interface between stress adaptation and cell death then is important for understanding redox biology and disease pathogenesis. Recent studies have found that one major sensor of redox signalling at this switch in cellular responses is autophagy. Autophagic activities are mediated by a complex molecular machinery including more than 30 Atg (AuTophaGy-related) proteins and 50 lysosomal hydrolases. Autophagosomes form membrane structures, sequester damaged, oxidized or dysfunctional intracellular components and organelles, and direct them to the lysosomes for degradation. This autophagic process is the sole known mechanism for mitochondrial turnover. It has been speculated that dysfunction of autophagy may result in abnormal mitochondrial function and oxidative or nitrative stress. Emerging investigations have provided new understanding of how autophagy of mitochondria (also known as mitophagy) is controlled, and the impact of autophagic dysfunction on cellular oxidative stress. The present review highlights recent studies on redox signalling in the regulation of autophagy, in the context of the basic mechanisms of mitophagy. Furthermore, we discuss the impact of autophagy on mitochondrial function and accumulation of reactive species. This is particularly relevant to degenerative diseases in which oxidative stress occurs over time, and dysfunction in both the mitochondrial and autophagic pathways play a role. C1 [Lee, Jisun; Giordano, Samantha; Zhang, Jianhua] Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Lee, Jisun; Giordano, Samantha; Zhang, Jianhua] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Zhang, Jianhua] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham, AL 35233 USA. RP Zhang, JH (reprint author), Univ Alabama, Ctr Free Rad Biol, 901 19th St S, Birmingham, AL 35294 USA. EM zhanja@uab.edu RI Carraro, Fabio/N-2613-2013; OI Carraro, Fabio/0000-0003-0771-042X; Zhang, Jianhua/0000-0002-2128-9574 FU National Institutes of Health [NIHR01-NS064090] FX This work was supported by the National Institutes of Health [grant number NIHR01-NS064090] and a Veterans Affairs merit award (to J.Z.). NR 290 TC 418 Z9 453 U1 32 U2 157 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 2012 VL 441 BP 523 EP 540 DI 10.1042/BJ20111451 PN 2 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874RV UT WOS:000298976700001 PM 22187934 ER PT J AU Naicker, DD Wang, BX Losina, E Zupkosky, J Bryan, S Reddy, S Jaggernath, M Mokgoro, M Goulder, PJR Kaufmann, DE Ndung'u, T AF Naicker, Dshanta D. Wang, Bingxia Losina, Elena Zupkosky, Jennifer Bryan, Susan Reddy, Shabashini Jaggernath, Manjeetha Mokgoro, Mammekwa Goulder, Philip J. R. Kaufmann, Daniel E. Ndung'u, Thumbi TI Association of IL-10-Promoter Genetic Variants With the Rate of CD4 T-Cell Loss, IL-10 Plasma Levels, and Breadth of Cytotoxic T-Cell Lymphocyte Response During Chronic HIV-1 Infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PROMOTER POLYMORPHISMS INFLUENCE; IL10 HAPLOTYPES; CYTOKINE GENES; INTERLEUKIN-10; AIDS; COHORT; HLA; SUSCEPTIBILITY; VACCINE; RISK AB Background. Interleukin-10 (IL-10) is a potent immunoregulatory cytokine. IL-10-promoter polymorphisms have been shown to affect human immunodeficiency virus type 1 (HIV-1) clinical outcomes but the underlying mechanisms are poorly understood. Methods. We investigated the relationship between IL-10-promoter variants, plasma cytokine levels, immune responses and markers of disease outcome in antiretroviral-naive HIV-1 chronically infected individuals from South Africa. Two IL-10-promoter single nucleotide polymorphisms (SNPs) were genotyped in 451 participants. Baseline plasma levels of select cytokines were measured for 112 individuals. Viral load, CD4(+) T-cell counts and HIV-1-specific interferon-gamma CD8(+) T-cell immune responses were measured at baseline. CD4(+) T-cell counts were measured longitudinally and rates of CD4(+) T-cell decline computed for 300 study subjects. Results. The minor IL-10-1082G and -592A variants occurred at frequencies of 0.31 and 0.34, respectively. The -592AA genotype associated significantly with attenuated loss of CD4(+) T cells (P = .0496). Individuals possessing -1082GG had significantly higher IL-10 levels compared to -1082AA/AG (P = .0006). The -592AA genotype was associated with greater breadth of virus-specific CD8(+) T-cell responses compared to CC and CA (P = .002 and .004 respectively). Conclusions. IL-10-promoter variants may influence the rate of HIV-1 disease progression by regulating IL-10 levels and the breadth of CD8(+) T-cell immune responses. C1 [Naicker, Dshanta D.; Bryan, Susan; Reddy, Shabashini; Jaggernath, Manjeetha; Mokgoro, Mammekwa; Ndung'u, Thumbi] Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, ZA-4013 Durban, South Africa. [Wang, Bingxia; Losina, Elena] Massachusetts Gen Hosp, Program HIV Outcomes Res, Boston, MA 02114 USA. [Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Nuffield Dept Med, Oxford OX1 2JD, England. [Zupkosky, Jennifer; Kaufmann, Daniel E.; Ndung'u, Thumbi] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Zupkosky, Jennifer; Kaufmann, Daniel E.; Ndung'u, Thumbi] Harvard Univ, Boston, MA 02115 USA. [Kaufmann, Daniel E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Ndung'u, T (reprint author), Univ KwaZulu Natal, HIV Pathogenesis Programme, Doris Duke Med Res Inst, Nelson R Mandela Sch Med, 719 Umbilo Rd, ZA-4013 Durban, South Africa. EM ndungu@ukzn.ac.za OI Ndung'u, Thumbi/0000-0003-2962-3992 FU National Institutes of Health (NIH) [ROI-AI067073, R01-AI46995, N01-AI-15422, RO1 HL-092565]; International AIDS Vaccine Initiative (IAVI); South African AIDS Vaccine Initiative; South African Department of Science and Technology through the National Research Foundation; Mark and Lisa Schwartz Foundation FX This work was supported by the National Institutes of Health (NIH, grants ROI-AI067073 and R01-AI46995, and contract #N01-AI-15422 and RO1 HL-092565), the International AIDS Vaccine Initiative (IAVI), and the South African AIDS Vaccine Initiative and the South African Department of Science and Technology through the National Research Foundation. Additional support was provided by the Mark and Lisa Schwartz Foundation. NR 39 TC 5 Z9 6 U1 0 U2 2 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 JAN 15 PY 2012 VL 54 IS 2 BP 294 EP 302 DI 10.1093/cid/cir811 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 866LZ UT WOS:000298383700023 PM 22100578 ER PT J AU Zhong, WD Liang, YX Lin, SX Li, L He, HC Bi, XC Han, ZD Dai, QS Ye, YK Chen, QB Wang, YS Zeng, GH Zhu, G Zhang, Z Chen, ZN Wu, CL AF Zhong, Wei-de Liang, Yu-xiang Lin, Sharron X. Li, Ling He, Hui-chan Bi, Xue-cheng Han, Zhao-dong Dai, Qi-shan Ye, Yong-kang Chen, Qing-biao Wang, Yue-sheng Zeng, Guo-hua Zhu, Gang Zhang, Zheng Chen, Zhi-nan Wu, Chin-Lee TI Expression of CD147 is associated with prostate cancer progression SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE CD147; prostate cancer; survival; progression ID MATRIX-METALLOPROTEINASE INDUCER; HEPATOCELLULAR-CARCINOMA; STROMAL INTERACTIONS; EMMPRIN; CELLS; INVASION; GROWTH; ANGIOGENESIS; INHIBITION; PROGNOSIS AB Novel molecular markers that are associated with prostate cancer (PCa) progression will provide valuable information in the diagnosis and treatment of the disease. Extracellular matrix metalloproteinase inducer (CD147) has been demonstrated to be involved in tumor invasion, metastasis, growth and survival. In our study, we examined whether the expression of CD147 can be used as a prognostic marker for predicting PCa progression. Tissue samples from 240 patients who received radical prostatectomy for PCa were obtained. CD147 expression in these samples was evaluated using immunohistochemical staining with a monoclonal antibody specifically against CD147. Increased expression of CD147 was correlated with higher Gleason scores (GS), positive surgical margin, prostate-specific antigen (PSA) failure, metastasis and reduced overall survival. Both univariate Cox regression analysis and multivariate analysis including competing biological variables demonstrated that increased CD147 expression was associated with increased risk for reduced PSA failure-free, metastasis-free and overall survival. KaplanMeier survival curves showed that the CD147 overexpression was a significant predictor for the PSA failure-free, metastasis-free and the overall survival in both pT2 and pT3 PCa patients. More significantly, higher expression of CD147 can serve as an independent prognostic predictor for PSA failure-free survival in PCa patients when they are stratified by GS. Our study results demonstrate the involvement of CD147 in PCa progression and suggest its potential role as an independent predictor of biochemical recurrence, development of metastasis and reduced overall survival in PCa. C1 [Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Wu, Chin-Lee] Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lin, Sharron X.; Wu, Chin-Lee] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zhong, Wei-de; He, Hui-chan; Bi, Xue-cheng; Han, Zhao-dong; Dai, Qi-shan; Ye, Yong-kang; Chen, Qing-biao; Wang, Yue-sheng; Zhang, Zheng] Guangzhou Med Coll, Guangzhou Municipal Peoples Hosp 1, Dept Urol, Guangzhou, Guangdong, Peoples R China. [Zhong, Wei-de; Liang, Yu-xiang; Zeng, Guo-hua] Guangdong Key Lab Urol, Guangzhou, Peoples R China. [Liang, Yu-xiang] So Med Univ, Grad Sch, Guangzhou, Guangdong, Peoples R China. [Li, Ling] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zeng, Guo-hua] Guangzhou Med Coll, Affiliated Hosp 1, Dept Urol, Guangzhou, Guangdong, Peoples R China. [Zhu, Gang] Beijing Hosp, Minist Publ Hlth, Dept Urol, Beijing, Peoples R China. [Chen, Zhi-nan] Fourth Mil Med Univ, Dept Cell Biol, Xian 710032, Peoples R China. [Chen, Zhi-nan] Fourth Mil Med Univ, Cell Engn Res Ctr, Xian 710032, Peoples R China. RP Wu, CL (reprint author), Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02115 USA. EM cwu2@partners.org OI Zhong, Weide/0000-0002-0430-2845 FU National High Technology Research and Development Project of China [2006AA02A245, 2007AA022001]; National Natural Science Foundation of China [30872960]; Guangdong Province (Provincial Key Research Laboratory on Prostate Disease), John and Claire Bertucci Prostate Cancer Foundation FX Grant sponsor: National High Technology Research and Development Project of China; Grant numbers: 2006AA02A245, 2007AA022001; Grant sponsor: National Natural Science Foundation of China; Grant number: 30872960; Grant sponsor: Guangdong Province (Provincial Key Research Laboratory on Prostate Disease), John and Claire Bertucci Prostate Cancer Foundation NR 28 TC 27 Z9 32 U1 2 U2 4 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 JAN 15 PY 2012 VL 130 IS 2 BP 300 EP 308 DI 10.1002/ijc.25982 PG 9 WC Oncology SC Oncology GA 864QI UT WOS:000298254400007 PM 21328337 ER PT J AU Fennelly, KP Radonovich, L AF Fennelly, Kevin P. Radonovich, Lewis TI Transocular Infection With Influenza and Efficacy of Barrier Methods SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID VIRUS C1 [Fennelly, Kevin P.; Radonovich, Lewis] US Dept Vet Affairs, Natl Ctr Occupat Hlth & Infect Control COHIC, Off Publ Hlth, Gainesville, FL 32608 USA. RP Fennelly, KP (reprint author), US Dept Vet Affairs, Natl Ctr Occupat Hlth & Infect Control COHIC, Off Publ Hlth, 1601 SW Archer Rd,151B, Gainesville, FL 32608 USA. EM kevin.fennelly@va.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2012 VL 205 IS 2 BP 349 EP 349 DI 10.1093/infdis/jir738 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 866NN UT WOS:000298387900027 PM 22124135 ER PT J AU Singh, N AF Singh, Nina TI How I Treat Cryptococcosis in Organ Transplant Recipients SO TRANSPLANTATION LA English DT Article DE Fungal infection; Cryptococcus; Transplant ID RECONSTITUTION INFLAMMATORY SYNDROME; VERSUS-HOST-DISEASE; AMPHOTERICIN-B; NEOFORMANS INFECTION; SOLID-ORGAN; PULMONARY CRYPTOCOCCOSIS; FUNGAL-INFECTIONS; ANTIFUNGAL AGENTS; RENAL-ALLOGRAFT; INTESTINAL TRANSPLANTATION AB Cryptococcosis is a significant opportunistic mycoses in organ transplant recipients. Topical developments in the field in the past few years have highlighted important issues and at the same time raised new questions regarding the management of this yeast. These include, for example, management of pretransplant cryptococcosis during transplant candidacy and timing of transplant in these instances; potential for donor transmission of cryptococcosis in light of recent fatal transmissions; and prevention and treatment of Cryptococcus-associated immune reconstitution syndrome. Discussed herein are challenges posed by these issues and evidence-based data to optimize the management of posttransplant cryptococcosis. C1 [Singh, Nina] VA Pittsburgh Healthcare Syst, Dept Med, Div Infect Dis, Pittsburgh, PA USA. [Singh, Nina] Univ Pittsburgh, Pittsburgh, PA USA. RP Singh, N (reprint author), Vet Adm Med Ctr, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. EM nis5@pitt.edu FU VA Pittsburgh Health Care System, Pittsburgh, PA FX This work was supported by resources and the use of facilities at the VA Pittsburgh Health Care System, Pittsburgh, PA. NR 66 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 2012 VL 93 IS 1 BP 17 EP 21 DI 10.1097/TP.0b013e318236cd1a PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 870HU UT WOS:000298660800003 PM 22015465 ER PT J AU Sornborger, AT Yokoo, T AF Sornborger, A. T. Yokoo, T. TI A multivariate, multitaper approach to detecting and estimating harmonic response in cortical optical imaging data SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Multitaper harmonic analysis; Multivariate statistics; Optical imaging; Primary visual cortex; Cortical maps ID VISUAL-CORTEX; FUNCTIONAL-ORGANIZATION; SPATIAL-FREQUENCY; ORIENTATION; EXTRACTION; SIGNAL; FIELD AB The efficiency and accuracy of cortical maps from optical imaging experiments have been improved using periodic stimulation protocols. The resulting data analysis requires the detection and estimation of periodic information in a multivariate dataset. To date, these analyses have relied on discrete Fourier transform (DFT) sinusoid estimates. Multitaper methods have become common statistical tools in the analysis of univariate time series that can give improved estimates. Here, we extend univariate multitaper harmonic analysis methods to the multivariate, imaging context. Given the hypothesis that a coherent oscillation across many pixels exists within a specified bandwidth, we investigate the problem of its detection and estimation in noisy data by constructing Hotelling's generalized T-2-test. We then extend the investigation of this problem in two contexts, that of standard canonical variate analysis (CVA) and that of generalized indicator function analysis (GIFA) which is often more robust in extracting a signal in spatially correlated noise. We provide detailed information on the fidelities of the mean estimates found with our methods and comparison with OFT estimates. Our results indicate that GIFA provides particularly good estimates of harmonic signals in spatially correlated noise and is useful for detecting small amplitude harmonic signals in applications such as biological imaging measurements where spatially correlated noise is common. We demonstrate the power of our methods with an optical imaging dataset of the periodic response to a periodically rotating oriented drifting grating stimulus experiment in cat visual cortex. (C) 2011 Elsevier B.V. All rights reserved. C1 [Sornborger, A. T.] Univ Georgia, Dept Math, Athens, GA 30602 USA. [Sornborger, A. T.] Univ Georgia, Fac Engn, Athens, GA 30602 USA. [Yokoo, T.] Massachusetts Gen Hosp, MGH Imaging, Div Abdominal Imaging & Intervent, Boston, MA 02115 USA. RP Sornborger, AT (reprint author), Univ Georgia, Dept Math, Athens, GA 30602 USA. EM ats@math.uga.edu; tyokoo@partners.org FU University of Georgia from the University of Georgia Research Foundation; NIH [EB005432, MH085973, NS070159] FX The authors would like to thank Udi Kaplan, Larry Sirovich and Bruce Knight for helpful discussions and help in the imaging laboratory. We would also like to thank David Thomson and Partha Mitra for helpful discussions and the Neuroinformatics course at the Marine Biological Laboratories in Woods Hole for providing an environment conducive to thinking about neural data analysis. ATS was funded by a University of Georgia Engineering Grant from the University of Georgia Research Foundation and NIH grants EB005432, MH085973 and NS070159. NR 29 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 EI 1872-678X J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 15 PY 2012 VL 203 IS 1 BP 254 EP 263 DI 10.1016/j.jneumeth.2011.09.018 PG 10 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 859SM UT WOS:000297896100030 PM 21970814 ER PT J AU O'Hagan, JJ Hernan, MA Walensky, RP Lipsitch, M AF O'Hagan, Justin J. Hernan, Miguel A. Walensky, Rochelle P. Lipsitch, Marc TI Apparent declining efficacy in randomized trials: examples of the Thai RV144 HIV vaccine and South African CAPRISA 004 microbicide trials SO AIDS LA English DT Editorial Material DE bias; clinical trial; HIV; prevention ID CONDOM EFFECTIVENESS; PREVENTION RESEARCH; REGRESSION-MODELS; FRAILTY MODELS; EVENT DATA; INFECTION; HETEROGENEITY; HAZARDS; BENEFIT; TIME C1 [O'Hagan, Justin J.; Hernan, Miguel A.; Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [O'Hagan, Justin J.; Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA 02115 USA. [Hernan, Miguel A.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol, Boston, MA 02115 USA. RP O'Hagan, JJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM johagan@hsph.harvard.edu OI Walensky, Rochelle P./0000-0002-8795-379X; Lipsitch, Marc/0000-0003-1504-9213 FU NIAID NIH HHS [R01 AI073127]; NIGMS NIH HHS [U54 GM088558, U54 GM088558-02, U54GM088558] NR 41 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 14 PY 2012 VL 26 IS 2 BP 123 EP 126 DI 10.1097/QAD.0b013e32834e1ce7 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 866KF UT WOS:000298378800001 PM 22045345 ER PT J AU Rasmussen, RA Siddappa, NB Lakhashe, SK Watkins, J Villinger, F Ibegbu, C Florese, RH Robert-Guroff, M Montefiori, DC Forthal, DN O'Connor, D Ruprecht, RM AF Rasmussen, Robert A. Siddappa, Nagadenahalli B. Lakhashe, Samir K. Watkins, Jennifer Villinger, Francois Ibegbu, Chris Florese, Ruth H. Robert-Guroff, Marjorie Montefiori, David C. Forthal, Donald N. O'Connor, David Ruprecht, Ruth M. CA Clade C Program Project Grp TI High-level, lasting antiviral immunity induced by a bimodal AIDS vaccine and boosted by live-virus exposure: prevention of viremia SO AIDS LA English DT Article DE AIDS; clade C; long-term immunity; prevention of viremia; simian/human immunodeficiency virus; vaccine ID SIMIAN-IMMUNODEFICIENCY-VIRUS; CLADE-C ENV; RHESUS MACAQUES; ANTIRETROVIRAL THERAPY; HIV VACCINES; HLA-B; REPLICATION; ANTIBODIES; INFECTION; LYMPHOCYTES AB Objective: To characterize the correlates of protection from systemic infection in a vaccinated rhesus macaque, RAt-9, which had been challenged sequentially with two related clade C simian/human immunodeficiency viruses (SHIV-Cs) yet remained aviremic for more than 5 years despite indirect evidence of cryptic infection. Design: To measure long-term anti-SHIV-C immunity, host genetics and gene-expression patterns for protective correlates. Methods: Long-term immune reactivity was evaluated and identification of virus in RAt-9 was attempted by RT-PCR analysis of concentrated plasma and blood transfer to CD8(+) cell-depleted infant macaques. Full MHC genotyping of RAt-9, TRIM5 alpha and KIR3DL allelic expression analysis of PBMC, and microarray gene expression analysis were performed. Results: All attempts to detect/isolate virus, including blood transfer to CD8(+) cell-depleted infant rhesus macaques, were negative, and the animal maintained normal levels of memory CD4(+) T cells in both peripheral blood and gut tissues. However, RAt-9 maintained high levels of anti-SHIV-C humoral and cellular immunity, including reactivity to nonvaccine neoantigens (Nef and Rev), up to 63 months postinitial challenge, suggesting chronic sub-threshold infection. RAt-9 expressed the Mamu A*001 allele negative for B*008 and B*017, had a B13 serotype, and had increased expression of killer-cell immunoglobulin-like receptors (KIRs) previously linked to favorable outcomes of lentiviral infection. Elements of the gene expression profiling coincided with genotyping results. RAt-9 also displayed CD8(+) cell noncytotoxic antiviral response (CNAR) activity. Conclusion: Monkey RAt-9 is the first example of a virus-exposed, persistently aviremic animal that has maintained long-term, high-level cellular and humoral antiviral immunity in the absence of an identifiable cryptic reservoir. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Rasmussen, Robert A.; Siddappa, Nagadenahalli B.; Lakhashe, Samir K.; Watkins, Jennifer; Ruprecht, Ruth M.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Rasmussen, Robert A.; Siddappa, Nagadenahalli B.; Lakhashe, Samir K.; Watkins, Jennifer; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Boston, MA USA. [Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Villinger, Francois; Ibegbu, Chris] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Florese, Ruth H.; Robert-Guroff, Marjorie] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Durham, NC USA. [Forthal, Donald N.] Univ Calif Irvine, Div Infect Dis, Dept Med, Sch Med, Irvine, CA 92717 USA. [O'Connor, David] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,JFB 809, Boston, MA 02215 USA. EM ruth_ruprecht@dfci.harvard.edu RI Lakhashe, Samir/F-1150-2014; OI Byrareddy, Siddappa /0000-0002-7423-1763; o'connor, david/0000-0003-2139-470X FU NIH [PO1 AI48240, RR-00165, RR00168]; Center for AIDS Research Immunology [P30 AI060354, P30 A01050409] FX Support is acknowledged by NIH grants PO1 AI48240 to R.A.R., S.L.H, J.G.E. and R.M.R., RR-00165 to the YNPRC, RR00168 to the NEPRC, and by Center for AIDS Research Immunology Core grants, P30 AI060354 and P30 A01050409. NR 39 TC 2 Z9 2 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 JAN 14 PY 2012 VL 26 IS 2 BP 149 EP 155 DI 10.1097/QAD.0b013e32834d3c4f PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 866KF UT WOS:000298378800004 PM 21941166 ER PT J AU Li, JZ Paredes, R Ribaudo, HJ Svarovskaia, ES Kozal, MJ Hullsiek, KH Miller, MD Bangsberg, DR Kuritzkes, DR AF Li, Jonathan Z. Paredes, Roger Ribaudo, Heather J. Svarovskaia, Evguenia S. Kozal, Michael J. Hullsiek, Katherine H. Miller, Michael D. Bangsberg, David R. Kuritzkes, Daniel R. TI Relationship between minority nonnucleoside reverse transcriptase inhibitor resistance mutations, adherence, and the risk of virologic failure SO AIDS LA English DT Article DE antiretroviral therapy; HIV-1 drug resistance; medication adherence; minority variants; virologic failure ID TREATMENT-NAIVE PATIENTS; RANDOMIZED CONTROLLED-TRIAL; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; HIV-1 INFECTION; INITIAL TREATMENT; EFAVIRENZ; EMTRICITABINE; REGIMENS; OUTCOMES AB Objectives: To evaluate the risk of virologic failure conferred by suboptimal adherence to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and minority NNRTI resistance mutations. Design: Pooled analysis of the risk of virologic failure conferred by minority NNRTI resistance mutations and NNRTI adherence from three studies of treatment-naive individuals initiating an NNRTI-based regimen. Methods: Participants from each study were categorized into both adherence quartiles (Q1-Q4) and four strata: at least 95%, 80-94%, 60-79%, and below 60%. Weighted Cox proportional hazard models were used to estimate the risk of virologic failure. Results: The majority of participants (N = 768) had high measured adherence, but those in the lowest adherence quartile had the highest proportion of participants with virologic failure and the risk of virologic failure increased step-wise with adherence below 95%. Detection of minority NNRTI drug resistance mutations increased the proportion of participants with virologic failure across adherence quartiles (Cochran-Mantel-Haenszel P < 0.001) and adherence strata [Cochran-Mantel-Haenszel P < 0.001; < 60% adherence, hazard ratio 1.7 (1.1-2.7), P = 0.02; 60-79% adherence, hazard ratio 1.2 (0.5-3.2), P = 0.67; 80-94% adherence, hazard ratio 2.5 (0.98-6.3), P = 0.06; >= 95% adherence, hazard ratio 3.6 (2.3-5.6), P < 0.001]. On multivariate analysis, the effect of minority variants was also most prominent at higher levels of medication adherence. Conclusions: The presence of minority NNRTI resistance mutations and NNRTI adherence were found to be independent predictors of virologic failure, but also modify each other's effects on virologic failure. In addition to the focus on medication adherence counseling, ultrasensitive HIV-1 drug resistance assays could play a role in optimizing the success rates of first-line antiretroviral therapy. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Li, Jonathan Z.; Kuritzkes, Daniel R.] Harvard Univ, Div Infect Dis, Brigham & Womens Hosp, Sch Med, Cambridge, MA 02139 USA. [Paredes, Roger] Hosp Badalona Germans Trias & Pujol, Irsi Caixa AIDS Res Inst, Badalona, Spain. [Paredes, Roger] Hosp Badalona Germans Trias & Pujol, Lluita SIDA Fdn, Badalona, Spain. [Ribaudo, Heather J.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Svarovskaia, Evguenia S.; Miller, Michael D.] Gilead Sci Inc, Foster City, CA 94404 USA. [Kozal, Michael J.] Yale Univ, Sch Med, New Haven, CT USA. [Kozal, Michael J.] VA CT Healthcare Syst, New Haven, CT USA. [Hullsiek, Katherine H.] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Li, JZ (reprint author), Harvard Univ, Div Infect Dis, Brigham & Womens Hosp, Sch Med, 65 Landsdowne St,Rm 435, Cambridge, MA 02139 USA. EM jli22@partners.org FU Bristol-Myers Squibb; Pfizer; Merck; Roche Diagnostics; IrsiCaixa AIDS Research Institute; Lluita contra la SIDA Foundation; ViiV Healthcare; Siemens; Boehringer Ingelheim; Gilead; Abbott; ViiV; Stanford University; Avexa; Boehringer-Ingelheim; GlaxoSmithKline; Oncolys; Roche; Tobira; Vertex; ViroStatistics; Clinical Investigator Training Program; Harvard/MIT Health Sciences and Technology - Beth Israel Deaconess Medical Center; Pfizer Inc.; Merck Co.; CHAIN; Collaborative HIV; Anti-HIV Drug Resistance Network [223131]; European Commission; NIH (Statistical and Data Management Center of the AIDS Clinical Trials Group) [U01 AI068634]; Harvard University CFAR [P30 AI060354]; VA; NIH [U01 AI042170, U01 AI 068636, K24 RR016482]; ACTG FX J.Z.L. has received research support from Bristol-Myers Squibb and has served as a consultant for Tibotec. R. P. has received consulting fees from Pfizer, Merck, Roche Diagnostics; the IrsiCaixa AIDS Research Institute and the Lluita contra la SIDA Foundation have received grant support from Pfizer, ViiV Healthcare, Siemens, Merck, and Boehringer Ingelheim for studies that R. P. serves as principal investigator. E. S. S. and M. D. M. are employees and stock-holders of Gilead Sciences, Inc. Yale University receives grant support from Merck, Pfizer, Gilead, Abbott, ViiV and Bristol-Myers Squibb for studies that M.J.K. serves as the principal investigator. M.J.K. receives royalties from patents owned by Stanford University for some HIV diagnostic tests. D. R. K. has served as a consultant to and/or has received research grant support from Abbott, Avexa, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck, Oncolys, Pfizer, Roche, Tobira, Vertex, ViroStatistics, and ViiV Healthcare. No other potential conflicts of interest relevant to this article were reported.; J.Z.L. is the recipient of a Clinical Investigator Training Program Fellowship: Harvard/MIT Health Sciences and Technology - Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc. and Merck & Co. R. P. was supported in part by the CHAIN, Collaborative HIV and Anti-HIV Drug Resistance Network, Integrated Project no. 223131, funded by the European Commission Framework 7 Program. H.J.R. is supported in part by grants from the NIH (Statistical and Data Management Center of the AIDS Clinical Trials Group U01 AI068634 and Harvard University CFAR P30 AI060354). M.J.K. is supported by a VA Merit Award. K. H. H. Hullsiek was supported in part by a grant from the NIH (U01 AI042170). D. R. K. is supported in part by grants from the NIH (U01 AI 068636, K24 RR016482) and an ACTG Virology Specialty Laboratory subcontract from the ACTG. NR 23 TC 43 Z9 44 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 14 PY 2012 VL 26 IS 2 BP 185 EP 192 DI 10.1097/QAD.0b013e32834e9d7d PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 866KF UT WOS:000298378800008 PM 22179227 ER PT J AU Venteo, S Bourane, S Mechaly, I Sar, C Samad, OA Puech, S Blostein, R Valmier, J Pattyn, A Carroll, P AF Venteo, Stephanie Bourane, Steeve Mechaly, Ilana Sar, Chamroeun Samad, Omar Abdel Puech, Sylvie Blostein, Rhoda Valmier, Jean Pattyn, Alexandre Carroll, Patrick TI Regulation of the Na,K-ATPase Gamma-Subunit FXYD2 by Runx1 and Ret Signaling in Normal and Injured Non-Peptidergic Nociceptive Sensory Neurons SO PLOS ONE LA English DT Article ID PERIPHERAL NERVOUS-SYSTEM; DORSAL-ROOT GANGLION; FOLLISTATIN-LIKE 1; NEUROPATHIC PAIN; RECEPTOR COMPONENTS; FUNCTIONAL-ROLE; CELLS; GDNF; NA+,K+-ATPASE; EXPRESSION AB Dorsal root ganglia (DRGs) contain the cell bodies of sensory neurons which relay nociceptive, thermoceptive, mechanoceptive and proprioceptive information from peripheral tissues toward the central nervous system. These neurons establish constant communication with their targets which insures correct maturation and functioning of the somato-sensory nervous system. Interfering with this two-way communication leads to cellular, electrophysiological and molecular modifications that can eventually cause neuropathic conditions. In this study we reveal that FXYD2, which encodes the gamma-subunit of the Na, K-ATPase reported so far to be mainly expressed in the kidney, is induced in the mouse DRGs at postnatal stages where it is restricted specifically to the TrkB-expressing mechanoceptive and Ret-positive/IB4-binding non-peptidergic nociceptive neurons. In non-peptidergic nociceptors, we show that the transcription factor Runx1 controls FXYD2 expression during the maturation of the somato-sensory system, partly through regulation of the tyrosine kinase receptor Ret. Moreover, Ret signaling maintains FXYD2 expression in adults as demonstrated by the axotomy-induced down-regulation of the gene that can be reverted by in vivo delivery of GDNF family ligands. Altogether, these results establish FXYD2 as a specific marker of defined sensory neuron subtypes and a new target of the Ret signaling pathway during normal maturation of the non-peptidergic nociceptive neurons and after sciatic nerve injury. C1 [Venteo, Stephanie; Bourane, Steeve; Mechaly, Ilana; Sar, Chamroeun; Valmier, Jean; Pattyn, Alexandre; Carroll, Patrick] Inst Neurosci Montpellier, INSERM, U1051, Montpellier, France. [Mechaly, Ilana; Valmier, Jean] Univ Montpellier 2, Montpellier, France. [Puech, Sylvie] Univ Montpellier 1, Montpellier, France. [Blostein, Rhoda] Montreal Gen Hosp, Res Inst, Dept Med, Montreal, PQ H3G 1A4, Canada. [Blostein, Rhoda] Montreal Gen Hosp, Res Inst, Dept Biochem, Montreal, PQ H3G 1A4, Canada. [Samad, Omar Abdel] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Neurobiol, Boston, MA 02115 USA. RP Venteo, S (reprint author), Inst Neurosci Montpellier, INSERM, U1051, Montpellier, France. EM carroll@univ-montp2.fr RI samad, omar/K-1921-2012 FU INSERM; CNRS; University of Montpellier II; Association Francaise contre les Myopathies FX This work was supported by INSERM, CNRS, University of Montpellier II and the Association Francaise contre les Myopathies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 9 Z9 9 U1 0 U2 1 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 JAN 13 PY 2012 VL 7 IS 1 AR e29852 DI 10.1371/journal.pone.0029852 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 906QI UT WOS:000301361500024 PM 22253804 ER PT J AU Kalay, E Sezgin, O Chellappa, V Mutlu, M Morsy, H Kayserili, H Kreiger, E Cansu, A Toraman, B Abdalla, EM Aslan, Y Pillai, S Akarsu, NA AF Kalay, Ersan Sezgin, Orhan Chellappa, Vasant Mutlu, Mehmet Morsy, Heba Kayserili, Hulya Kreiger, Elmar Cansu, Aysegul Toraman, Bayram Abdalla, Ebtesam Mohammed Aslan, Yakup Pillai, Shiv Akarsu, Nurten A. TI Mutations in RIPK4 Cause the Autosomal-Recessive Form of Popliteal Pterygium Syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NF-KAPPA-B; BARTSOCAS-PAPAS-SYNDROME; C-ASSOCIATED KINASE; APICAL ECTODERMAL RIDGE; IKK-ALPHA; SIGNALING PATHWAYS; PROTEIN-KINASE; KERATINOCYTE DIFFERENTIATION; MICE LACKING; FAMILY AB The autosomal-recessive form of popliteal pterygium syndrome, also known as Bartsocas-Papas syndrome, is a rare, but frequently lethal disorder characterized by marked popliteal pterygium associated with multiple congenital malformations. Using Affymetrix 250K SNP array genotyping and homozygosity mapping, we mapped this malformation syndrome to chromosomal region 21q22.3. Direct sequencing of RIPK4 (receptor-interacting serine/threonine kinase protein 4) showed a homozygous transversion (c.362T>A) that causes substitution of a conserved isoleucine with asparagine at amino acid position 121 (p.Ile121Asn) in the serine/threonine kinase domain of the protein. Additional pathogenic mutations-a homozygous transition (c.551C>T) that leads to a missense substitution (p.Thr184Ile) at a conserved position and a homozygous one base-pair insertion mutation (c.777_778insA) predicted to lead to a premature stop codon (p.Arg260ThrfsX14) within the kinase domain-were observed in two families. Molecular modeling of the kinase domain showed that both the Ile121 and Thr184 positions are critical for the protein's stability and kinase activity. Luciferase reporter assays also demonstrated that these mutations are critical for the catalytic activity of RIPK4. RIPK4 mediates activation of the nuclear factor-kappa B (NF-kappa B) signaling pathway and is required for keratinocyte differentiation and craniofacial and limb development. The phenotype of Ripk4(-/-) mice is consistent with the human phenotype presented herein. Additionally, the spectrum of malformations observed in the presented families is similar, but less severe than the conserved helix-loop-helix ubiquitous kinase (CHUK)-deficient human fetus phenotype; known as Cocoon syndrome; this similarity indicates that RIPK4 and CHUK might function via closely related pathways to promote keratinocyte differentiation and epithelial growth. C1 [Kalay, Ersan] Karadeniz Tech Univ, Fac Med, Dept Med Biol, TR-61080 Trabzon, Turkey. [Sezgin, Orhan; Toraman, Bayram] Karadeniz Tech Univ, Inst Hlth Sci, Dept Med Biol, TR-61080 Trabzon, Turkey. [Chellappa, Vasant; Pillai, Shiv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. [Mutlu, Mehmet; Aslan, Yakup] Karadeniz Tech Univ, Fac Med, Dept Pediat, TR-61080 Trabzon, Turkey. [Morsy, Heba; Abdalla, Ebtesam Mohammed] Univ Alexandria, Med Res Inst, Dept Human Genet, Alexandria 21661, Egypt. [Kayserili, Hulya] Istanbul Univ, Istanbul Fac Med, Dept Med Genet, TR-34094 Istanbul, Turkey. [Kreiger, Elmar] Radboud Univ Nijmegen, Med Ctr, Ctr Mol & Biomol Informat, NL-6525 GA Nijmegen, Netherlands. [Cansu, Aysegul] Karadeniz Tech Univ, Fac Med, Dept Radiol, TR-61080 Trabzon, Turkey. [Akarsu, Nurten A.] Hacettepe Univ, Fac Med, Dept Med Genet, Gene Mapping Lab, TR-06100 Ankara, Turkey. RP Kalay, E (reprint author), Karadeniz Tech Univ, Fac Med, Dept Med Biol, TR-61080 Trabzon, Turkey. EM ersankalay@hotmail.com RI Akarsu, Nurten/E-9758-2013; OI Akarsu, Nurten/0000-0001-5432-0032; Morsy, Heba/0000-0002-9047-0959 FU Karadeniz Technical University [2009.114.001.05]; Scientific and Technological Research Council of Turkey (TUBITAK) under the E-RARE network CRANIRARE consortium [1085420, 1085418, R07197KS] FX We thank all the family members that participated in this study and M. Livaoglu, N. Karacal, A. Yildirim, K. Baydar, and O. Aliyazicioglu for their indispensible technical assistance. This study was supported by the Karadeniz Technical University Research Fund (grant 2009.114.001.05 to E.K.) and the Scientific and Technological Research Council of Turkey (TUBITAK) (1085420 to N.A.A. and 1085418 to H.K.) grants under the E-RARE network CRANIRARE consortium (project no. R07197KS). NR 55 TC 26 Z9 29 U1 1 U2 6 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 JAN 13 PY 2012 VL 90 IS 1 BP 76 EP 85 DI 10.1016/j.ajhg.2011.11.014 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 880LR UT WOS:000299409100007 PM 22197489 ER PT J AU Jeanne, M Labelle-Dumais, C Jorgensen, J Kauffman, WB Mancini, GM Favor, J Valant, V Greenberg, SM Rosand, J Gould, DB AF Jeanne, Marion Labelle-Dumais, Cassandre Jorgensen, Jeff Kauffman, W. Berkeley Mancini, Grazia M. Favor, Jack Valant, Valerie Greenberg, Steven M. Rosand, Jonathan Gould, Douglas B. TI COL4A2 Mutations Impair COL4A1 and COL4A2 Secretion and Cause Hemorrhagic Stroke SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RECURRENT INTRACEREBRAL HEMORRHAGE; CEREBRAL AMYLOID ANGIOPATHY; BASEMENT-MEMBRANE COLLAGEN; IV COLLAGEN; CAENORHABDITIS-ELEGANS; HANAC SYNDROME; IDENTIFICATION; DROSOPHILA; DISEASE; BRAIN AB Collagen, type IV, alpha 1 (COL4A1) and alpha 2 (COL4A2) form heterotrimers and are abundant components of basement membranes, including those of the cerebral vasculature. COL4A1 mutations are an increasingly recognized cause of multisystem disorders, including highly penetrant cerebrovascular disease and intracerebral hemorrhage (ICH). Because COL4A1 and COL4A2 are structurally and functionally associated, we hypothesized that variants in COL4A2 would also cause ICH. We sequence COL4A2 in 96 patients with ICH and identify three rare, nonsynonymous coding variants in four patients that are not present in a cohort of 144 ICH-free individuals. All three variants change evolutionarily conserved amino acids. Using a cellular assay, we show that these putative mutations cause intracellular accumulation of COL4A1 and COL4A2 at the expense of their secretion, which supports their pathogenecity. Furthermore, we show that Col4a2 mutant mice also have completely penetrant ICH and that mutations in mouse and human lead to retention of COL4A1 and COL4A2 within the endoplasmic reticulum (ER). Importantly, two of the three putative mutations found in patients trigger ER stress and activate the unfolded protein response. The identification of putative COL4A2 mutations that might contribute to ICH in human patients provides insight into the pathogenic mechanisms of this disease. Our data suggest that COL4A2 mutations impair COL4A1 and COL4A2 secretion and can also result in cytotoxicity. Finally, our findings suggest that, collectively, mutations in COL4A1 and COL4A2 contribute to sporadic cases of ICH. C1 [Jeanne, Marion; Labelle-Dumais, Cassandre; Jorgensen, Jeff; Kauffman, W. Berkeley; Gould, Douglas B.] Univ Calif San Francisco, Dept Ophthalmol, Inst Human Genet, San Francisco, CA 94143 USA. [Jeanne, Marion; Labelle-Dumais, Cassandre; Jorgensen, Jeff; Kauffman, W. Berkeley; Gould, Douglas B.] Univ Calif San Francisco, Dept Anat, Inst Human Genet, San Francisco, CA 94143 USA. [Mancini, Grazia M.] Erasmus MC, Dept Clin Genet, NL-3015 GJ Rotterdam, Netherlands. [Favor, Jack] Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany. [Valant, Valerie; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Valant, Valerie; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Valant, Valerie; Rosand, Jonathan] Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. RP Gould, DB (reprint author), Univ Calif San Francisco, Dept Ophthalmol, Inst Human Genet, San Francisco, CA 94143 USA. EM gouldd@vision.ucsf.edu FU American Heart Association; National Institutes of Health (NIH)- National Institute of Neurological Disorders and Stroke [R01NS059727]; Research To Prevent Blindness; NIH- National Eye Institute (NEI) [R01EY019887]; NEI [EY02162] FX This study was funded by a research grant from the American Heart Association (D.B.G.) and by National Institutes of Health (NIH)- National Institute of Neurological Disorders and Stroke grant R01NS059727 (S.M.G. and J.R.). Salary support was also provided by Research To Prevent Blindness (C.L.D.), and NIH- National Eye Institute (NEI) grant R01EY019887 (B.K.). Additional support was provided by a core grant from the NEI (EY02162) and a Research To Prevent Blindness Unrestricted Grant (UCSF Department of Ophthalmology). NR 37 TC 45 Z9 47 U1 2 U2 13 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 JAN 13 PY 2012 VL 90 IS 1 BP 91 EP 101 DI 10.1016/j.ajhg.2011.11.022 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 880LR UT WOS:000299409100009 PM 22209247 ER PT J AU Moldovan, GL Dejsuphong, D Petalcorin, MIR Hofmann, K Takeda, S Boulton, SJ D'Andrea, AD AF Moldovan, George-Lucian Dejsuphong, Donniphat Petalcorin, Mark I. R. Hofmann, Kay Takeda, Shunichi Boulton, Simon J. D'Andrea, Alan D. TI Inhibition of Homologous Recombination by the PCNA-Interacting Protein PARI SO MOLECULAR CELL LA English DT Article ID STRAND-BREAK-REPAIR; MAINTAINS GENOMIC STABILITY; CANCER SUSCEPTIBILITY GENE; FANCONI-ANEMIA; DNA-REPAIR; VERTEBRATE CELLS; REPLICATION FORK; HELICASE; RAD51; BRCA2 AB Inappropriate homologous recombination (HR) causes genomic instability and cancer. In yeast, the UvrD family helicase Srs2 is recruited to sites of DNA replication by SUMO-modified PCNA, where it acts to restrict HR by disassembling toxic RAD51 nucleofilaments. How human cells control recombination at replication forks is unknown. Here, we report that the protein PARI, containing a UvrD-like helicase domain, is a PCNA-interacting partner required for preservation of genome stability in human and DT40 chicken cells. Using cell-based and biochemical assays, we show that PARI restricts unscheduled recombination by interfering with the formation of RAD51-DNA HR structures. Finally, we show that PARI knockdown suppresses the genomic instability of Fanconi Anemia/BRCA pathway-deficient cells. Thus, we propose that PARI is a long sought-after factor that suppresses inappropriate recombination events at mammalian replication forks. C1 [Moldovan, George-Lucian; Dejsuphong, Donniphat; D'Andrea, Alan D.] Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02215 USA. [Petalcorin, Mark I. R.; Boulton, Simon J.] London Res Inst, DNA Damage Response Lab, Canc Res UK, S Mimms EN6 3LD, Herts, England. [Hofmann, Kay] Miltenyi Biotec, Bioinformat Grp, D-51429 Bergisch Gladbach, Germany. [Takeda, Shunichi] Kyoto Univ, Dept Radiat Genet, Grad Sch Med, Sakyo Ku, Kyoto 6068501, Japan. RP D'Andrea, AD (reprint author), Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Sch Med, 44 Binney St, Boston, MA 02215 USA. EM alan_dandrea@dfci.harvard.edu OI George-Lucian, Moldovan/0000-0003-3825-149X; Petalcorin, Mark/0000-0001-8211-9440 FU International Human Frontiers Science Program; Susan G. Komen Breast Cancer Foundation; National Institutes of Health [R01DK43889, R01HL52725, P01HL048546, P01CA092584]; Deutsche Forschungsgemeinschaft [SPP1365] FX We would like to thank Maria Jasin for the DR-GFP reporter, Lisa Moreau for chromosome aberration analyses, Kailin Yang for initial PARI cloning, and Dipanjan Chowdhury, Geoffrey Shapiro, Timur Yusufzai, Deepa Kushwaha, Stefan Muller, Kevin O'Connor, Younghoon Kee, Patrizia Vinciguerra, and Hyungjin Kim for materials and advice. G.L.M. is supported by postdoctoral fellowships from the International Human Frontiers Science Program and the Susan G. Komen Breast Cancer Foundation. This study was supported by National Institutes of Health grants R01DK43889, R01HL52725, P01HL048546, and P01CA092584 to A.D.D. and by Deutsche Forschungsgemeinschaft priority program SPP1365 to K.H. NR 45 TC 84 Z9 89 U1 4 U2 13 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 JAN 13 PY 2012 VL 45 IS 1 BP 75 EP 86 DI 10.1016/j.molcel.2011.11.010 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 879AE UT WOS:000299301300011 PM 22153967 ER PT J AU Kroshinsky, D Hoang, MP Hasserjian, RP AF Kroshinsky, Daniela Hoang, Mai P. Hasserjian, Robert P. TI Case 1-2012: An 82-Year-Old Man with Persistent Ulcers on the Hands SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PYODERMA-GANGRENOSUM; INFLIXIMAB C1 [Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Hoang, Mai P.; Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kroshinsky, Daniela] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hoang, Mai P.; Hasserjian, Robert P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kroshinsky, D (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. FU Harvard Medical School Department of Continuing Education and Department of Pathology; Massachusetts General Hospital; Beth Israel Deaconess Medical Center; Brigham and Women's Hospital FX This case was presented at the postgraduate course Dermatopathology Update, sponsored by the Harvard Medical School Department of Continuing Education and Department of Pathology, Massachusetts General Hospital, Beth Israel Deaconess Medical Center, and Brigham and Women's Hospital. NR 9 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 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 12 PY 2012 VL 366 IS 2 BP 166 EP 174 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 874VA UT WOS:000298985000013 PM 22236228 ER PT J AU Butler, MO Imataki, O Yamashita, Y Tanaka, M Ansen, S Berezovskaya, A Metzler, G Milstein, MI Mooney, MM Murray, AP Mano, H Nadler, LM Hirano, N AF Butler, Marcus O. Imataki, Osamu Yamashita, Yoshihiro Tanaka, Makito Ansen, Sascha Berezovskaya, Alla Metzler, Genita Milstein, Matthew I. Mooney, Mary M. Murray, Andrew P. Mano, Hiroyuki Nadler, Lee M. Hirano, Naoto TI Ex Vivo Expansion of Human CD8(+) T Cells Using Autologous CD4(+) T Cell Help SO PLOS ONE LA English DT Article ID CHRONIC VIRAL-INFECTION; TUMOR-INFILTRATING LYMPHOCYTES; ANTIGEN-PRESENTING CELLS; TRANSFER THERAPY; METASTATIC MELANOMA; OVARIAN-CANCER; CUTTING EDGE; IN-VIVO; ADOPTIVE IMMUNOTHERAPY; CD27 EXPRESSION AB Background: Using in vivo mouse models, the mechanisms of CD4(+) T cell help have been intensively investigated. However, a mechanistic analysis of human CD4(+) T cell help is largely lacking. Our goal was to elucidate the mechanisms of human CD4(+) T cell help of CD8(+) T cell proliferation using a novel in vitro model. Methods/Principal Findings: We developed a genetically engineered novel human cell-based artificial APC, aAPC/mOKT3, which expresses a membranous form of the anti-CD3 monoclonal antibody OKT3 as well as other immune accessory molecules. Without requiring the addition of allogeneic feeder cells, aAPC/mOKT3 enabled the expansion of both peripheral and tumor-infiltrating T cells, regardless of HLA-restriction. Stimulation with aAPC/mOKT3 did not expand Foxp3(+) regulatory T cells, and expanded tumor infiltrating lymphocytes predominantly secreted Th1-type cytokines, interferonthis aAPC-based system, the presence of autologous CD4(+) T cells was associated with significantly improved CD8(+) T cell expansion in vitro. The CD4(+) T cell derived cytokines IL-2 and IL-21 were necessary but not sufficient for this effect. However, CD4(+) T cell help of CD8(+) T cell proliferation was partially recapitulated by both adding IL-2/IL-21 and by upregulation of IL21 receptor on CD8(+) T cells. Conclusions: We have developed an in vitro model that advances our understanding of the immunobiology of human CD4(+) T cell help of CD8(+) T cells. Our data suggests that human CD4(+) T cell help can be leveraged to expand CD8(+) T cells in vitro. C1 [Butler, Marcus O.; Imataki, Osamu; Tanaka, Makito; Ansen, Sascha; Berezovskaya, Alla; Metzler, Genita; Milstein, Matthew I.; Mooney, Mary M.; Murray, Andrew P.; Nadler, Lee M.; Hirano, Naoto] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Butler, Marcus O.; Imataki, Osamu; Tanaka, Makito; Ansen, Sascha; Nadler, Lee M.; Hirano, Naoto] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Butler, Marcus O.; Imataki, Osamu; Tanaka, Makito; Ansen, Sascha; Nadler, Lee M.; Hirano, Naoto] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Yamashita, Yoshihiro; Mano, Hiroyuki] Jichi Med Univ, Div Funct Genom, Shimotsuke, Tochigi, Japan. [Mano, Hiroyuki] Univ Tokyo, Dept Med Genom, Tokyo, Japan. [Hirano, Naoto] Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Immune Therapy Program, Toronto, ON M4X 1K9, Canada. [Hirano, Naoto] Univ Toronto, Dept Immunol, Toronto, ON, Canada. RP Butler, MO (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM nhirano@uhnres.utoronto.ca FU Madeleine Franchi Ovarian Research Fund; Dunkin Donuts Rising Stars Awards; Cancer Research Institute; NIH [K22 CA129240, R01 CA148673]; American Society of Hematology FX This work was supported by the Madeleine Franchi Ovarian Research Fund (MOB), Dunkin Donuts Rising Stars Awards (MOB and NH), a grant from the Cancer Research Institute (LMN), NIH grant K22 CA129240 (NH), NIH grant R01 CA148673 (NH), and the American Society of Hematology Scholar Award (NH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 71 TC 12 Z9 12 U1 1 U2 7 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 JAN 12 PY 2012 VL 7 IS 1 AR e30229 DI 10.1371/journal.pone.0030229 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 906OY UT WOS:000301357100047 PM 22279573 ER PT J AU Wu, XQ Zhu, MJ Fletcher, JA Giobbie-Hurder, A Hodi, FS AF Wu, Xinqi Zhu, Meijun Fletcher, Jonathan A. Giobbie-Hurder, Anita Hodi, F. Stephen TI The Protein Kinase C Inhibitor Enzastaurin Exhibits Antitumor Activity against Uveal Melanoma SO PLOS ONE LA English DT Article ID LUNG-CANCER CELLS; HETEROTRIMERIC G-PROTEINS; BETA INHIBITOR; BRAF MUTATIONS; INDUCED APOPTOSIS; MULTIPLE-MYELOMA; PKC ISOFORMS; MAPK PATHWAY; GLIOMA-CELLS; COLON-CANCER AB GNAQ mutations at codon 209 have been recently identified in approximately 50% of uveal melanomas (UM) and are reported to be oncogenic through activating the MAPK/Erk1/2 pathway. Protein kinase C ( PKC) is a component of signaling from GNAQ to Erk1/2. Inhibition of PKC might regulate GNAQ mutation-induced Erk1/2 activation, resulting in growth inhibition of UM cells carrying GNAQ mutations. UM cells carrying wild type or mutant GNAQ were treated with the PKC inhibitor enzastaurin. Effects on proliferation, apoptosis, and signaling events were evaluated. Enzastaurin downregulated the expression of several PKC isoforms including PKC beta II PKC theta, PKC epsilon and/or their phosphorylation in GNAQ mutated cells. Downregulation of these PKC isoforms in GNAQ mutated cells by shRNA resulted in reduced viability. Enzastaurin exhibited greater antiproliferative effect on GNAQ mutant cells than wild type cells through induction of G1 arrest and apoptosis. Enzastaurin-induced G1 arrest was associated with inhibition of Erk1/2 phosphorylation, downregulation of cyclin D1, and accumulation of cyclin dependent kinase inhibitor p27(Kip1). Furthermore, enzastaurin reduced the expression of antiapoptotic Bcl-2 and survivin in GNAQ mutant cells. Inhibition of Erk1/2 phosphorylation with a MEK specific inhibitor enhanced the sensitivity of GNAQ wild type cells to enzastaurin, accompanied by p27(Kip1) accumulation and/or inhibition of enzastaurin-induced survivin and Bcl-2 upregulation. PKC inhibitors such as enzastaurin have activity against UM cells carrying GNAQ mutations through inhibition of the PKC/Erk1/2 pathway and induction of G1 arrest and apoptosis. Inhibition of the PKC pathway provides a basis for clinical investigation in patients with UM. C1 [Wu, Xinqi; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Xinqi; Zhu, Meijun; Fletcher, Jonathan A.; Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA USA. [Wu, Xinqi; Hodi, F. Stephen] Dana Farber Brigham & Womens Canc Ctr, Melanoma Program, Boston, MA USA. [Zhu, Meijun; Fletcher, Jonathan A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Wu, XQ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM stephen_hodi@dfci.harvard.edu FU Sharon Crowley Martin Memorial Fund for Melanoma Research; Dana-Farber Cancer Institute FX This work was supported in part by Sharon Crowley Martin Memorial Fund for Melanoma Research (FSH.) and Malcolm, Emily Mac Naught Fund for Melanoma Research (FSH.) at Dana-Farber Cancer Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 42 Z9 45 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 JAN 12 PY 2012 VL 7 IS 1 AR e29622 DI 10.1371/journal.pone.0029622 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 906OY UT WOS:000301357100016 ER PT J AU Musallam, KM Sankaran, VG Cappellini, MD Duca, L Nathan, DG Taher, AT AF Musallam, Khaled M. Sankaran, Vijay G. Cappellini, Maria Domenica Duca, Lorena Nathan, David G. Taher, Ali T. TI Fetal hemoglobin levels and morbidity in untransfused patients with beta-thalassemia intermedia SO BLOOD LA English DT Article ID SICKLE-CELL-DISEASE; RISK-FACTORS; IRON OVERLOAD; ERYTHROPOIESIS; MANAGEMENT; HBS1L-MYB; VARIANTS; BCL11A; RATES; PAIN AB To evaluate the association between fetal hemoglobin (HbF) levels and morbidity in beta-thalassemia intermedia (TI), we analyzed data from 63 untransfused patients who had also never received HbF induction therapy. Patient records were reviewed for any history of 10 predefined morbidities. Laboratory measurements for markers of ineffective erythropoiesis were also obtained. The mean age of patients was 32.1 years, 47.6% were males, and the median HbF level was 37.2%. HbF levels correlated positively with total hemoglobin, yet negatively with growth differentiation factor-15 and non-transferrin-bound iron levels. Median HbF levels were significantly lower in patients with the majority of evaluated morbidities than in those without. There was a strong negative adjusted linear correlation between the HbF level and the total number of morbidities (R(2) = 0.825, P < .001). The HbF threshold of 63.7% had 95.5% sensitivity and 100% specificity for ensuring absence of morbidity. There exists a strong association between HbF levels and morbidity in the subset of untransfused patients with TI. (Blood. 2012;119(2):364-367) C1 [Taher, Ali T.] Amer Univ Beirut Med Ctr, Dept Internal Med, Beirut, Lebanon. [Musallam, Khaled M.; Cappellini, Maria Domenica; Duca, Lorena] Ist Ricovero & Cura Carattere Sci IRCCS Ca Granda, Dept Med & Med Specialties, Milan, Italy. [Sankaran, Vijay G.; Nathan, David G.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Taher, AT (reprint author), Amer Univ Beirut Med Ctr, Dept Internal Med, POB 11-0236,Riad El Solh 1107 2020, Beirut, Lebanon. EM ataher@aub.edu.lb RI Duca, Lorena/K-6909-2012; OI Musallam, Khaled/0000-0003-3935-903X; Taher, Ali/0000-0001-8515-2238 NR 22 TC 30 Z9 31 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 12 PY 2012 VL 119 IS 2 BP 364 EP 367 DI 10.1182/blood-2011-09-382408 PG 4 WC Hematology SC Hematology GA 878PL UT WOS:000299268900013 PM 22096240 ER PT J AU Walker, LJ Kang, YH Smith, MO Tharmalingham, H Ramamurthy, N Fleming, VM Sahgal, N Leslie, A Oo, Y Geremia, A Scriba, TJ Hanekom, WA Lauer, GM Lantz, O Adams, DH Powrie, F Barnes, E Klenerman, P AF Walker, Lucy J. Kang, Yu-Hoi Smith, Matthew O. Tharmalingham, Hannah Ramamurthy, Narayan Fleming, Vicki M. Sahgal, Natasha Leslie, Alistair Oo, Ye Geremia, Alessandra Scriba, Thomas J. Hanekom, Willem A. Lauer, Georg M. Lantz, Olivier Adams, David H. Powrie, Fiona Barnes, Eleanor Klenerman, Paul TI Human MAIT and CD8 alpha alpha cells develop from a pool of type-17 precommitted CD8(+) T cells SO BLOOD LA English DT Article ID NATURAL-KILLER; CD161 EXPRESSION; CUTTING EDGE; NKT CELLS; POPULATION; RECEPTOR; THYMUS; IL-15; DIFFERENTIATION; HOMEOSTASIS AB Human mucosal associated invariant T (MAIT) CD8(+) and Tc17 cells are important tissue-homing cell populations, characterized by high expression of CD161 ((++)) and type-17 differentiation, but their origins and relationships remain poorly defined. By transcriptional and functional analyses, we demonstrate that a pool of polyclonal, precommitted type-17 CD161(++)CD8 alpha beta(+) T cells exist in cord blood, from which a prominent MAIT cell (TCR V alpha 7.2(+)) population emerges postnatally. During this expansion, CD8 alpha alpha T cells appear exclusively within a CD161(++)CD8(+)/MAIT subset, sharing cytokine production, chemokine-receptor expression, TCR-usage, and transcriptional profiles with their CD161(++)CD8 alpha beta(+) counterparts. Our data demonstrate the origin and differentiation pathway of MAIT-cells from a naive type-17 precommitted CD161(++)CD8(+) T-cell pool and the distinct phenotype and function of CD8 alpha alpha cells in man. (Blood. 2012;119(2):422-433) C1 [Geremia, Alessandra; Powrie, Fiona; Klenerman, Paul] Univ Oxford, Nuffield Dept Med, Translat Gastroenterol Unit, Oxford OX1 3SY, England. [Sahgal, Natasha] Univ Oxford, Bioinformat Grp, Wellcome Trust Ctr Human Genet, Oxford OX1 3SY, England. [Leslie, Alistair] Univ Oxford, Weatherall Inst Mol Med, Oxford OX1 3SY, England. [Oo, Ye; Adams, David H.] Univ Birmingham, Liver Res Ctr, Birmingham, W Midlands, England. [Oo, Ye; Adams, David H.] Univ Birmingham, NIHR Biomed Res Unit, Inst Biomed Res, Birmingham, W Midlands, England. [Scriba, Thomas J.; Hanekom, Willem A.] Univ Cape Town, S African TB Vaccine Initiat, Sch Child & Adolescent Hlth, ZA-7925 Cape Town, South Africa. [Scriba, Thomas J.; Hanekom, Willem A.] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa. [Lauer, Georg M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gastroenterol, Boston, MA USA. [Lantz, Olivier] Inst Curie, Dept Biol Tumeurs, Paris, France. [Barnes, Eleanor; Klenerman, Paul] Natl Inst Hlth Res Oxford Biomed Res Ctr, Oxford, England. RP Klenerman, P (reprint author), Univ Oxford, Nuffield Dept Med, Translat Gastroenterol Unit, Peter Medawar Bldg Pathogen Res, Oxford OX1 3SY, England. EM paul.klenerman@ndm.ox.ac.uk RI Adams, David/C-9092-2009; Lantz, Olivier/J-4960-2012; Scriba, Thomas/H-3633-2013 OI Lantz, Olivier/0000-0003-3161-7719; FU Medical Research Council; Wellcome Trust [WT091663MA]; NIHR (Oxford); James Martin School for the 21st Century (Oxford); NIAID [NIH NIAID 1U19AI082630-01] FX This research was supported by the Medical Research Council, the Wellcome Trust (WT091663MA), the NIHR Biomedical Research Program (Oxford), the James Martin School for the 21st Century (Oxford), and the NIAID U19 Bio-defense Program (NIH NIAID 1U19AI082630-01). NR 39 TC 79 Z9 79 U1 1 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 12 PY 2012 VL 119 IS 2 BP 422 EP 433 DI 10.1182/blood-2011-05-353789 PG 12 WC Hematology SC Hematology GA 878PL UT WOS:000299268900019 PM 22086415 ER PT J AU Dagan, LN Jiang, XY Bhatt, S Cubedo, E Rajewsky, K Lossos, IS AF Dagan, Liat Nadav Jiang, Xiaoyu Bhatt, Shruti Cubedo, Elena Rajewsky, Klaus Lossos, Izidore S. TI miR-155 regulates HGAL expression and increases lymphoma cell motility SO BLOOD LA English DT Article ID INDUCED CYTIDINE DEAMINASE; CENTER-SPECIFIC PROTEIN; HODGKIN LYMPHOMA; GENE-EXPRESSION; TRANSGENIC MICE; LIGHT-CHAIN; B-CELLS; MICRORNA-155; PATHWAY; SURVIVAL AB HGAL, a prognostic biomarker in patients with diffuse large B-cell lymphoma and classic Hodgkin lymphoma, inhibits lymphocyte and lymphoma cell motility by activating the RhoA signaling cascade and interacting with actin and myosin proteins. Although HGAL expression is limited to germinal center (GC) lymphocytes and GC-derived lymphomas, little is known about its regulation. miR-155 is implicated in control of GC reaction and lymphomagenesis. We demonstrate that miR-155 directly down-regulates HGAL expression by binding to its 3'-untranslated region, leading to decreased RhoA activation and increased spontaneous and chemoattractant-induced lymphoma cell motility. The effects of miR-155 on RhoA activation and cell motility can be rescued by transfection of HGAL lacking the miR-155 binding site. This inhibitory effect of miR-155 suggests that it may have a key role in the loss of HGAL expression on differentiation of human GC B cells to plasma cell. Furthermore, this effect may contribute to lymphoma cell dissemination and aggressiveness, characteristic of activated B cell-like diffuse large B-cell lymphoma typically expressing high levels of miR-155 and lacking HGAL expression. (Blood. 2012; 119(2): 513-520) C1 [Dagan, Liat Nadav; Jiang, Xiaoyu; Bhatt, Shruti; Cubedo, Elena; Lossos, Izidore S.] Univ Miami, Dept Med, Sylvester Comprehens Canc Ctr, Div Hematol Oncol, Miami, FL 33136 USA. [Rajewsky, Klaus] Harvard Univ, Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Lossos, Izidore S.] Univ Miami, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA. RP Lossos, IS (reprint author), Univ Miami, Dept Med, Sylvester Comprehens Canc Ctr, Div Hematol Oncol, 1475 NW 12th Ave,D8-4, Miami, FL 33136 USA. EM ilossos@med.miami.edu FU National Institutes of Health [CA109335, CA122105]; Dwoskin Family foundation; Fidelity foundation FX I.S.L. was supported by the National Institutes of Health (grants CA109335 and CA122105) and the Dwoskin Family and Fidelity foundations. NR 48 TC 30 Z9 37 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 12 PY 2012 VL 119 IS 2 BP 513 EP 520 DI 10.1182/blood-2011-08-370536 PG 8 WC Hematology SC Hematology GA 878PL UT WOS:000299268900029 PM 22096245 ER PT J AU Patnaik, MM Lasho, TL Hodnefield, JM Knudson, RA Ketterling, RP Garcia-Manero, G Steensma, DP Pardanani, A Hanson, CA Tefferi, A AF Patnaik, Mrinal M. Lasho, Terra L. Hodnefield, Janice M. Knudson, Ryan A. Ketterling, Rhett P. Garcia-Manero, Guillermo Steensma, David P. Pardanani, Animesh Hanson, Curtis A. Tefferi, Ayalew TI SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value SO BLOOD LA English DT Article ID ANEMIA; MYELOFIBROSIS AB SF3B1 mutations were recently reported in myelodysplastic syndromes (MDSs), especially in the presence of ring sideroblasts (RSs). We sought to define the interaction between SF3B1 mutations, morphology, karyotype, and prognosis in MDS with more than or equal to 15% RS (MDS-RS). We studied 107 patients with MDS-RS, including 48 with refractory anemia with RS (RARS), 43 with refractory cytopenia with multilineage dysplasia (RCMD)-RS, 11 with refractory anemia with excess blasts-1 (RAEB1)-RS, and 5 with RAEB2-RS. SF3B1 mutations were detected in 53 (similar to 50%) patients: 35 RARS (73%), 16 RCMD-RS (37%), and 2 RAEB1-RS (18%). In univariate analysis, the presence of SF3B1 mutations was associated with better overall (P < .01) and leukemia-free (P < .01) survival; however, in both instances, significance was completely accounted for by World Health Organization morphologic risk categorization. In other words, when RARS and RCMD-RS were analyzed separately, there was no additional prognostic value from the presence or absence of SF3B1 mutations. (Blood. 2012; 119(2): 569-572) C1 [Patnaik, Mrinal M.; Lasho, Terra L.; Pardanani, Animesh; Tefferi, Ayalew] Mayo Clin, Div Hematol, Rochester, MN 55905 USA. [Hodnefield, Janice M.; Hanson, Curtis A.] Mayo Clin, Div Hematopathol, Rochester, MN 55905 USA. [Knudson, Ryan A.; Ketterling, Rhett P.] Mayo Clin, Cytogenet Div, Rochester, MN 55905 USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tefferi, A (reprint author), Mayo Clin, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu OI Steensma, David/0000-0001-5130-9284 FU NCI NIH HHS [P30 CA016672] NR 17 TC 98 Z9 103 U1 2 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 12 PY 2012 VL 119 IS 2 BP 569 EP 572 DI 10.1182/blood-2011-09-377994 PG 4 WC Hematology SC Hematology GA 878PL UT WOS:000299268900035 PM 22096241 ER PT J AU Chen, T Benmohamed, R Kim, J Smith, K Amante, D Morimoto, RI Kirsch, DR Ferrante, RJ Silverman, RB AF Chen, Tian Benmohamed, Radhia Kim, Jinho Smith, Karen Amante, Daniel Morimoto, Richard I. Kirsch, Donald R. Ferrante, Robert J. Silverman, Richard B. TI ADME-Guided Design and Synthesis of Aryloxanyl Pyrazolone Derivatives To Block Mutant Superoxide Dismutase 1 (SOD1) Cytotoxicity and Protein Aggregation: Potential Application for the Treatment of Amyotrophic Lateral Sclerosis SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOTOR-NEURON DEGENERATION; GULF-WAR VETERANS; ALS; MUTATIONS; RILUZOLE; DISEASE; MICE; GENE; CYTOCHROME-P450; SULFOXIDATION AB Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease currently without a cure: The arylsulfanyl pyrazolone (ASP) scaffold was one of the active scaffolds identified in a cell-based high throughput screening assay targeting mutant Cu/Zn superoxide dismutase 1 (SOD 1) induced toxicity and aggregation as a marker for ALS. The initial ASP hit compounds were potent and had favorable ADME properties but had poor microsomal and plasma stability. Here, we identify the microsomal metabolite and describe synthesized analogues of these ASP compounds to address the rapid metabolism. Both in vitro potency and pharmacological properties of the ASP scaffold have been dramatically improved via chemical modification to the corresponding sulfone and ether derivatives. One of the ether analogues (13), with superior potency and in vitro pharmacokinetic properties, was tested in vivo for its pharmacokinetic profile, brain penetration, and efficacy in an ALS mouse model. The analogue showed sustained blood and brain levels in vivo and significant activity in the mouse model of ALS, thus validating the new aryloxanyl pyrazolone scaffold as an important novel therapeutic lead for the treatment of this neurodegenerative disorder. C1 [Chen, Tian; Silverman, Richard B.] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA. [Benmohamed, Radhia; Kirsch, Donald R.] Cambria Pharmaceut, Cambridge, MA 02142 USA. [Kim, Jinho; Amante, Daniel; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15213 USA. [Kim, Jinho; Amante, Daniel; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Kim, Jinho; Amante, Daniel; Ferrante, Robert J.] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA 15213 USA. [Kim, Jinho; Amante, Daniel; Ferrante, Robert J.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr GR H 00, Pittsburgh, PA 15206 USA. [Smith, Karen] Bedford VA Med Ctr, Bedford, MA 01730 USA. [Morimoto, Richard I.] Northwestern Univ, Rice Inst Biomed Res, Dept Mol Biosci, Evanston, IL 60208 USA. [Silverman, Richard B.] Northwestern Univ, Ctr Mol Innovat & Drug Discovery, Chem Life Proc Inst, Dept Mol Biosci, Evanston, IL 60208 USA. RP Silverman, RB (reprint author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA. EM Agman@chem.northwestern.edu FU National Institutes of Health [1R43NS057849]; ALS Association (TREAT); Department of Defense [AL093052]; Center for ALS Research at the Univesity of Pittsburgh, PA FX We thank the National Institutes of Health (Grant 1R43NS057849), the ALS Association (TREAT program), the Department of Defense (Grant AL093052), and the Center for ALS Research at the Univesity of Pittsburgh, PA, for their generous support of the research project. The authors are grateful to Biogen Idec Inc. for carrying out the in vivo rat PK profiling tests, in vitro P450 reversible inhibition study, the plasma binding affinity assay, and the hERG inhibition assays; and MDS Pharma Service (now Ricerca Biosciences, LLC) for carrying out the LeadProfilingScreen of 13. NR 50 TC 19 Z9 19 U1 3 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 12 PY 2012 VL 55 IS 1 BP 515 EP 527 DI 10.1021/jm2014277 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 874SQ UT WOS:000298978800040 PM 22191331 ER PT J AU Baselga, J Cortes, J Kim, SB Im, SA Hegg, R Im, YH Roman, L Pedrini, JL Pienkowski, T Knott, A Clark, E Benyunes, MC Ross, G Swain, SM AF Baselga, Jose Cortes, Javier Kim, Sung-Bae Im, Seock-Ah Hegg, Roberto Im, Young-Hyuck Roman, Laslo Pedrini, Jose Luiz Pienkowski, Tadeusz Knott, Adam Clark, Emma Benyunes, Mark C. Ross, Graham Swain, Sandra M. CA CLEOPATRA Study Grp TI Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; PHASE-II TRIAL; MONOCLONAL-ANTIBODY; RECEPTOR; THERAPY; ERBB3; INHIBITOR; TOXICITY; PROTEINS; EFFICACY AB BACKGROUND The anti-human epidermal growth factor receptor 2 (HER2) humanized monoclonal antibody trastuzumab improves the outcome in patients with HER2-positive metastatic breast cancer. However, most cases of advanced disease eventually progress. Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of trastuzumab, and combination therapy with the two antibodies has shown promising activity and an acceptable safety profile in phase 2 studies involving patients with HER2-positive breast cancer. METHODS We randomly assigned 808 patients with HER2-positive metastatic breast cancer to receive placebo plus trastuzumab plus docetaxel (control group) or pertuzumab plus trastuzumab plus docetaxel (pertuzumab group) as first-line treatment until the time of disease progression or the development of toxic effects that could not be effectively managed. The primary end point was independently assessed progression-free survival. Secondary end points included overall survival, progression-free survival as assessed by the investigator, the objective response rate, and safety. RESULTS The median progression-free survival was 12.4 months in the control group, as compared with 18.5 months in the pertuzumab group (hazard ratio for progression or death, 0.62; 95% confidence interval, 0.51 to 0.75; P<0.001). The interim analysis of overall survival showed a strong trend in favor of pertuzumab plus trastuzumab plus docetaxel. The safety profile was generally similar in the two groups, with no increase in left ventricular systolic dysfunction; the rates of febrile neutropenia and diarrhea of grade 3 or above were higher in the pertuzumab group than in the control group. CONCLUSIONS The combination of pertuzumab plus trastuzumab plus docetaxel, as compared with placebo plus trastuzumab plus docetaxel, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival, with no increase in cardiac toxic effects. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT00567190.) C1 [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Baselga, Jose] Harvard Univ, Sch Med, Boston, MA USA. [Cortes, Javier] Vall dHebron Inst Oncol, Barcelona, Spain. [Kim, Sung-Bae] Univ Ulsan, Dept Oncol, Asan Med Ctr, Coll Med, Seoul, South Korea. [Im, Seock-Ah] Seoul Natl Univ, Coll Med, Dept Internal Med, Div Hematol & Med Oncol, Seoul 151, South Korea. [Im, Young-Hyuck] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol & Med Oncol,Dept Internal Med, Seoul, South Korea. [Hegg, Roberto] Univ Sao Paulo, Hosp Perola Byington, Sao Paulo, Brazil. [Hegg, Roberto] Univ Sao Paulo, Fac Med, Sao Paulo, Brazil. [Roman, Laslo] Leningrad Reg Oncol Dispensary, St Petersburg, Russia. [Pedrini, Jose Luiz] Conceicao Hosp, Mastol Unit, Ctr Pesquisas Med & Ensaios Clin, Porto Alegre, RS, Brazil. [Pienkowski, Tadeusz] Ctr Onkol, Warsaw, Poland. [Knott, Adam; Clark, Emma; Ross, Graham] Roche, Welwyn Garden City, England. [Benyunes, Mark C.] Genentech Inc, San Francisco, CA 94080 USA. [Swain, Sandra M.] MedStar Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Lawrence House 108, Boston, MA 02114 USA. EM jbaselga@partners.org RI Im, Seock-Ah/J-5620-2012; Aktas, Bahriye/F-1019-2014; Calvo, Lourdes/M-2352-2014; Schmidt, Marcus/H-3383-2013; OI Schmidt, Marcus/0000-0003-1365-2414; Cortes, Javier/0000-0001-7623-1583; Ciruelos, Eva /0000-0002-2796-1042; Swain, Sandra/0000-0002-1320-3830 FU F. Hoffmann-La Roche/Genentech, a member of the Roche Group FX Supported by F. Hoffmann-La Roche/Genentech, a member of the Roche Group. Support for writing assistance by a third party (Vilma Graupner, Ph.D.) was provided by F. Hoffmann-La Roche. NR 28 TC 837 Z9 871 U1 14 U2 124 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 JAN 12 PY 2012 VL 366 IS 2 BP 109 EP 119 DI 10.1056/NEJMoa1113216 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 874VA UT WOS:000298985000005 PM 22149875 ER PT J AU Kim, JH Malhotra, R Chiampas, G d'Hemecourt, P Troyanos, C Cianca, J Smith, RN Wang, TJ Roberts, WO Thompson, PD Baggish, AL AF Kim, Jonathan H. Malhotra, Rajeev Chiampas, George d'Hemecourt, Pierre Troyanos, Chris Cianca, John Smith, Rex N. Wang, Thomas J. Roberts, William O. Thompson, Paul D. Baggish, Aaron L. CA Race Associated Cardiac Arrest TI Cardiac Arrest during Long-Distance Running Races SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; AMERICAN-HEART-ASSOCIATION; SUDDEN-DEATH; HYPERTROPHIC CARDIOMYOPATHY; PLATELET ACTIVATION; STANDARDIZED RATES; BOSTON MARATHON; EXERTION; ATHEROSCLEROSIS; RUNNERS AB BACKGROUND Approximately 2 million people participate in long-distance running races in the United States annually. Reports of race-related cardiac arrests have generated concern about the safety of this activity. METHODS We assessed the incidence and outcomes of cardiac arrest associated with marathon and half-marathon races in the United States from January 1, 2000, to May 31, 2010. We determined the clinical characteristics of the arrests by interviewing survivors and the next of kin of nonsurvivors, reviewing medical records, and analyzing postmortem data. RESULTS Of 10.9 million runners, 59 (mean [+/-SD] age, 42+/-13 years; 51 men) had cardiac arrest (incidence rate, 0.54 per 100,000 participants; 95% confidence interval [CI], 0.41 to 0.70). Cardiovascular disease accounted for the majority of cardiac arrests. The incidence rate was significantly higher during marathons (1.01 per 100,000; 95% CI, 0.72 to 1.38) than during half-marathons (0.27; 95% CI, 0.17 to 0.43) and among men (0.90 per 100,000; 95% CI, 0.67 to 1.18) than among women (0.16; 95% CI, 0.07 to 0.31). Male marathon runners, the highest-risk group, had an increased incidence of cardiac arrest during the latter half of the study decade (2000-2004, 0.71 per 100,000 [95% CI, 0.31 to 1.40]; 2005-2010, 2.03 per 100,000 [95% CI, 1.33 to 2.98]; P = 0.01). Of the 59 cases of cardiac arrest, 42 (71%) were fatal (incidence, 0.39 per 100,000; 95% CI, 0.28 to 0.52). Among the 31 cases with complete clinical data, initiation of bystander-administered cardiopulmonary resuscitation and an underlying diagnosis other than hypertrophic cardiomyopathy were the strongest predictors of survival. CONCLUSIONS Marathons and half-marathons are associated with a low overall risk of cardiac arrest and sudden death. Cardiac arrest, most commonly attributable to hypertrophic cardiomyopathy or atherosclerotic coronary disease, occurs primarily among male marathon participants; the incidence rate in this group increased during the past decade. C1 [Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, Boston, MA 02114 USA. [Smith, Rex N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [d'Hemecourt, Pierre] Harvard Univ, Sch Med, Boston, MA USA. [d'Hemecourt, Pierre] Childrens Hosp, Div Sports Med, Boston, MA 02115 USA. [Troyanos, Chris] Boston Athlet Assoc, Boston, MA USA. [Chiampas, George] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Cianca, John] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Roberts, William O.] Univ Minnesota, Sch Med, Dept Family Med, St Paul, MN 55108 USA. [Thompson, Paul D.] Univ Connecticut, Sch Med, Hartford Hosp, Div Cardiol, Hartford, CT 06112 USA. RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, 55 Fruit St,YAW-5800, Boston, MA 02114 USA. EM abaggish@partners.org OI Roberts, William O/0000-0003-4517-4330 FU Regeneron; Lupin Pharmaceuticals; GlaxoSmithKline; Genomas; Novartis; Furiex Pharmaceuticals; Merck; Pfizer; AstraZeneca; Kowa; Abbott FX Dr. Roberts reports holding a board membership with UCare Minnesota, receiving writing fees from Runner's World, and serving as an unpaid, volunteer medical director for the Medtronic Twin Cities Marathon; and Dr. Thompson, receiving consulting fees from Regeneron, Furiex Pharmaceuticals, and Lupin Pharmaceuticals, legal fees for expert testimony in cases related to cardiac arrest in exercise- and statin-related muscle injury, grant funding from GlaxoSmithKline, Genomas, Novartis, Furiex Pharmaceuticals, B. Braun, and Aventis, lecture fees from Merck, Pfizer, AstraZeneca, Kowa, Abbott, and GlaxoSmithKline, support for the development of educational presentations from Merck, and holding stock in Zoll Medical, J.A. Wiley Publishing, General Electric, Zimmer, Medtronic, Johnson & Johnson, Sanofi-Aventis, and Abbott. No other potential conflict of interest relevant to this article was reported. NR 39 TC 163 Z9 164 U1 4 U2 23 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 JAN 12 PY 2012 VL 366 IS 2 BP 130 EP 140 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 874VA UT WOS:000298985000007 PM 22236223 ER PT J AU Mao, YD Zhang, JZ AF Mao, Youdong Zhang, Jinzhong TI Understanding Thermodynamic Competitivity between Biopolymer Folding and Misfolding under Large-Scale Intermolecular Interactions SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID I-MOTIF STRUCTURE; ENERGY LANDSCAPE; RICH STRAND; DNA; PROTEIN; KINETICS; OLIGODEOXYNUCLEOTIDES; PHOSPHODIESTER; POLYPEPTIDE; RESOLUTION AB Cooperativity is a hallmark of spontaneous biopolymer folding. The presence of intermolecular interactions could create off-pathway misfolding structures and suppress folding cooperativity. This raises the hypothesis that thermodynamic competitivity between off-pathway misfolding and on-pathway folding may intervene with cooperativity and govern biopolymer folding dynamics under conditions permitting large-scale intermolecular interactions. Here we report direct imaging and theoretical modeling of thermodynamic competitivity between biopolymer folding and misfolding under such conditions, using a two-dimensional array of proton-fueled DNA molecular motors packed at the maximal density as a model system. Time-resolved liquid-phase atomic force microscopy with enhanced phase contrast revealed that the misfolding and folding intermediates transiently self-organize into spatiotemporal patterns on the nanoscale in thermodynamic states far away from equilibrium as a result of thermodynamic competitivity. Computer simulations using a novel cellular-automaton network model provide quantitative insights into how large-scale intermolecular interactions correlate the structural dynamics of individual biomolecules together at the systems level. C1 [Mao, Youdong] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Microbiol & Immunobiol, Boston, MA 02215 USA. [Zhang, Jinzhong] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. RP Mao, YD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Microbiol & Immunobiol, Boston, MA 02215 USA. EM youdong_mao@dfci.harvard.edu OI zhang, jinzhong/0000-0001-7026-1300 NR 52 TC 1 Z9 1 U1 2 U2 28 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 JAN 11 PY 2012 VL 134 IS 1 BP 631 EP 639 DI 10.1021/ja209534c PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 903AB UT WOS:000301084200100 PM 22126310 ER PT J AU Bastien, D Gallagher, A Tremblay, J Vannasing, P Theriault, M Lassonde, M Lepore, F AF Bastien, Danielle Gallagher, Anne Tremblay, Julie Vannasing, Phetsamone Theriault, Martin Lassonde, Maryse Lepore, Franco TI Specific functional asymmetries of the human visual cortex revealed by functional near-infrared spectroscopy SO BRAIN RESEARCH LA English DT Article DE Retinotopic mapping; Visual cortex asymmetries; Vertical asymmetry; fNIRS; Optical imaging ID DIFFUSE OPTICAL TOMOGRAPHY; RETINOTOPIC ORGANIZATION; HUMAN BRAIN; CORTICAL ACTIVATION; OXYGENATION CHANGES; SPATIAL-RESOLUTION; AREAS; FIELD; STRIATE; INFANTS AB Based on multiple invasive reports and neuroimaging studies, it is well established that the cytoarchitecture of the visual cortex is related to its functional organization, namely, its retinotopy. The present study aimed to further investigate retinotopic mapping as well as specific vertical and horizontal functional asymmetries within the human visual cortex using functional near-infrared spectroscopy (fNIRS). Black and white wedge checkerboard stimuli were randomly presented to the four visual field (VF) quadrants of eight healthy adults in order to quantify and compare the localization and the amplitude of hemodynamic cortical responses to each VF quadrant. Results showed the expected activation in the contralateral hemisphere, with respect to the side of the stimulated quadrant. We also measured significantly stronger activations in the upper visual cortex when low hemifield stimuli were presented compared to activations in the lower visual cortex when upper hemifield stimuli were shown, especially when the stimulation was presented in the right visual field. These findings confirm the vertical asymmetry of the visual cortex previously reported by neuroimaging and behavioral studies. More importantly, the present work confirms the reliability of the fNIRS technique for functional mapping of the human brain. (C) 2011 Elsevier B.V. All rights reserved. C1 [Lepore, Franco] Univ Montreal, Dept Psychol, Canada Res Chair Cognit Neurosci, Ctr Rech Neuropsychol & Cognit, Montreal, PQ H3C 3J7, Canada. [Bastien, Danielle; Gallagher, Anne; Tremblay, Julie; Vannasing, Phetsamone; Theriault, Martin; Lassonde, Maryse; Lepore, Franco] Ctr Hosp Univ St Justine, Ctr Rech, Montreal, PQ H3T 1C5, Canada. [Gallagher, Anne] Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,Dept Neurol, Boston, MA 02114 USA. RP Lepore, F (reprint author), Univ Montreal, Dept Psychol, Canada Res Chair Cognit Neurosci, Ctr Rech Neuropsychol & Cognit, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada. EM franco.lepore@umontreal.ca FU Canada Research Chair in Cognitive Neurosciences; Canada Research Chair in Developmental Neuropsychology; Canadian Institutes of Health Research (CIHR) FX This work was supported by the Canada Research Chair in Cognitive Neurosciences held by Franco Lepore, Ph.D., the Canada Research Chair in Developmental Neuropsychology held by Maryse Lassonde, Ph.D. as well as scholarships by the Canadian Institutes of Health Research (CIHR) awarded to Anne Gallagher, Ph.D. NR 41 TC 3 Z9 3 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 11 PY 2012 VL 1431 BP 62 EP 68 DI 10.1016/j.brainres.2011.11.008 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 895CD UT WOS:000300472900007 PM 22137561 ER PT J AU Zilberstein, Y Liberman, MC Corfas, G AF Zilberstein, Yael Liberman, M. Charles Corfas, Gabriel TI Inner Hair Cells Are Not Required for Survival of Spiral Ganglion Neurons in the Adult Cochlea SO JOURNAL OF NEUROSCIENCE LA English DT Article ID INDUCED HEARING-LOSS; GUINEA-PIG COCHLEA; MICE LACKING; THIAMINE TRANSPORTER; MAMMALIAN COCHLEA; EFFERENT FIBERS; TIME-COURSE; DEGENERATION; MOUSE; NERVE AB Studies of sensorineural hearing loss have long suggested that survival of spiral ganglion neurons (SGNs) depends on trophic support provided by their peripheral targets, the inner hair cells (IHCs): following ototoxic drugs or acoustic overexposure, IHC death is rapid whereas SGN degeneration is always delayed. However, recent noise-trauma studies show that SGNs can die even when hair cells survive, and transgenic mouse models show that supporting cell dysfunction can cause SGN degeneration in the absence of IHC pathology. To reexamine this issue, we studied a model of IHC loss that does not involve noise or ototoxic drugs. Mice lacking the gene for the high-affinity thiamine transporter (Slc19a2) have normal cochlear structure and function when fed a regular (thiamine-rich) diet. However, dietary thiamine restriction causes widespread, rapid (within 10 d) loss of IHCs. Using this model, we show that SGNs can survive for months after IHC loss, indicating that (1) IHCs are not necessary for neuronal survival, (2) neuronal loss in the other hearing loss models is likely due to effects of the trauma on the sensory neurons or other inner ear cells, and (3) that other cells, most likely supporting cells of the organ of Corti, are the main source of SGN survival factors. These results overturn a long-standing dogma in the study of sensorineural hearing loss and highlight the importance of cochlear supporting cells in neuronal survival in the adult inner ear. C1 [Zilberstein, Yael; Corfas, Gabriel] Childrens Hosp Boston, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Zilberstein, Yael; Corfas, Gabriel] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Liberman, M. Charles; Corfas, Gabriel] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. RP Corfas, G (reprint author), Childrens Hosp Boston, FM Kirby Neurobiol Ctr, 3 Blackfan Circle,CLS Room 12256, Boston, MA 02115 USA. EM Charles_Liberman@meei.harvard.edu; gabriel.corfas@childrens.harvard.edu FU National Institutes of Health [RO1 DC0188, R01 DC04820, P30 DC5029]; Department of Otolaryngology and Communication Enhancement, Children's Hospital Boston; Intellectual and Developmental Disabilities Research Center NIH [P30-HD 18655] FX This work was supported by National Institutes of Health Grants RO1 DC0188 (M. C. L.), R01 DC04820 (G. C.), and P30 DC5029 (M. C. L.); the Department of Otolaryngology and Communication Enhancement, Children's Hospital Boston (G. C); and Intellectual and Developmental Disabilities Research Center NIH Grant P30-HD 18655 (G. C.). The skillful assistance of Leslie Dodds, Constance Miller, and Bethany Taylor is gratefully acknowledged. NR 34 TC 63 Z9 65 U1 2 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 11 PY 2012 VL 32 IS 2 BP 405 EP 410 DI 10.1523/JNEUROSCI.4678-11.2012 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 876QE UT WOS:000299121800002 PM 22238076 ER PT J AU Gladman, SJ Huang, WL Lim, SN Dyall, SC Boddy, S Kang, JX Knight, MM Priestley, JV Michael-Titus, AT AF Gladman, Stacy J. Huang, Wenlong Lim, Siew-Na Dyall, Simon C. Boddy, Sophie Kang, Jing X. Knight, Martin M. Priestley, John V. Michael-Titus, Adina T. TI Improved Outcome after Peripheral Nerve Injury in Mice with Increased Levels of Endogenous Omega-3 Polyunsaturated Fatty Acids SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SPINAL-CORD-INJURY; ACTIVATING TRANSCRIPTION FACTOR-3; DOCOSAHEXAENOIC ACID; HIPPOCAMPAL-NEURONS; NEURITE OUTGROWTH; NEUROPROTECTIN D1; CHRONIC DISEASES; CELL-DEATH; RAT; OMEGA-3-FATTY-ACIDS AB Functional recovery after a peripheral nerve injury (PNI) is often poor. There is a need for therapies that protect neurons against injury and enhance regeneration. Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to have therapeutic potential in a variety of neurological disorders, including acute traumatic injury. The objective of this study was to assess the neuroprotective and proregenerative potential of omega-3 PUFAs in PNI. We investigated this in mice that express the fat-1 gene encoding for omega-3 fatty acid desaturase, which leads to an increase in endogenous omega-3 PUFAs and a concomitant decrease in omega-6 PUFAs. Dorsal root ganglion (DRG) neurons from wild-type or fat-1 mice were subjected to a mechanical strain or hypoxic injury, and cell death was assessed using ethidium homodimer-1 labeling. The fat-1 background appears to confer robust neuroprotection against both injuries. We then examined the early functional and morphological changes in wild-type and fat-1 mice after a sciatic nerve crush. An accelerated functional recovery 7 d after injury was seen in fat-1 mice when assessed using von Frey filaments and the sciatic nerve functional index. These observations were also mapped to changes in injury-related markers. The injury-induced expression of ATF-3 was decreased in the DRG of fat-1 mice, whereas the axons detected 6 mm distal to the crush were increased. Fat-1 animals also had some protection against muscle atrophy after injury. In conclusion, both in vitro and in vivo experiments support the idea that a higher endogenous omega-3 PUFA could lead to beneficial effects after a PNI. C1 [Gladman, Stacy J.; Huang, Wenlong; Lim, Siew-Na; Dyall, Simon C.; Boddy, Sophie; Priestley, John V.; Michael-Titus, Adina T.] Queen Mary Univ London, Barts & London Sch Med & Dent, Ctr Neurosci & Trauma, Blizard Inst, London E1 2AT, England. [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Knight, Martin M.] Queen Mary Univ London, Med Engn Grp, Sch Mat Sci & Engn, London E1 4NS, England. [Dyall, Simon C.] Roehampton Univ, Dept Life Sci, Whitelands Coll, London SW15 4JD, England. [Lim, Siew-Na] Chang Gung Mem Hosp, Dept Neurol, Taipei 105, Taiwan. [Lim, Siew-Na] Chang Gung Univ, Coll Med, Taipei 105, Taiwan. RP Gladman, SJ (reprint author), Queen Mary Univ London, Barts & London Sch Med & Dent, Ctr Neurosci & Trauma, Blizard Inst, London E1 2AT, England. EM s.gladman@qmul.ac.uk RI Huang, Wenlong/P-2025-2016; OI Gladman, Stacy/0000-0002-7112-4516; Dyall, Simon/0000-0001-7591-4219 FU Biotechnology and Biological Sciences Research Council; Medical Research Council/Engineering and Physical Sciences Research Council FX We gratefully acknowledge support through a Biotechnology and Biological Sciences Research Council doctoral training grant PhD studentship (S.J.G.) and a Medical Research Council/Engineering and Physical Sciences Research Council Discipline Bridging Initiative award. NR 44 TC 20 Z9 20 U1 0 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 11 PY 2012 VL 32 IS 2 BP 563 EP 571 DI 10.1523/JNEUROSCI.3371-11.2012 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 876QE UT WOS:000299121800017 PM 22238091 ER PT J AU Rice, TW Wheeler, AP Thompson, BT AF Rice, Todd W. Wheeler, Arthur P. Thompson, B. Taylor TI Supplementation in Acute Lung Injury Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID GUIDELINES; OUTCOMES; TRIAL C1 [Rice, Todd W.; Wheeler, Arthur P.] Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Rice, TW (reprint author), Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA. EM todd.rice@vanderbilt.edu NR 6 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 11 PY 2012 VL 307 IS 2 BP 145 EP 146 DI 10.1001/jama.2011.1985 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 875NP UT WOS:000299038300018 ER PT J AU Yourman, LC Lee, SJ Schonberg, MA Widera, EW Smith, AK AF Yourman, Lindsey C. Lee, Sei J. Schonberg, Mara A. Widera, Eric W. Smith, Alexander K. TI Prognostic Indices for Older Adults A Systematic Review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID NURSING-HOME RESIDENTS; MORTALITY-RELATED FACTORS; ADMINISTRATIVE DATA; BREAST-CANCER; MEDICAL LITERATURE; 1-YEAR MORTALITY; ELDERLY-PATIENTS; DECISION-MAKING; AORTIC-ANEURYSM; USERS GUIDES AB Context To better target services to those who may benefit, many guidelines recommend incorporating life expectancy into clinical decisions. Objective To assess the quality and limitations of prognostic indices for mortality in older adults through systematic review. Data Sources We searched MEDLINE, EMBASE, Cochrane, and Google Scholar from their inception through November 2011. Study Selection We included indices if they were validated and predicted absolute risk of mortality in patients whose average age was 60 years or older. We excluded indices that estimated intensive care unit, disease-specific, or in-hospital mortality. Data Extraction For each prognostic index, we extracted data on clinical setting, potential for bias, generalizability, and accuracy. Results We reviewed 21 593 titles to identify 16 indices that predict risk of mortality from 6 months to 5 years for older adults in a variety of clinical settings: the community (6 indices), nursing home (2 indices), and hospital (8 indices). At least 1 measure of transportability (the index is accurate in more than 1 population) was tested for all but 3 indices. By our measures, no study was free from potential bias. Although 13 indices had C statistics of 0.70 or greater, none of the indices had C statistics of 0.90 or greater. Only 2 indices were independently validated by investigators who were not involved in the index's development. Conclusion We identified several indices for predicting overall mortality in different patient groups; future studies need to independently test their accuracy in heterogeneous populations and their ability to improve clinical outcomes before their widespread use can be recommended. JAMA. 2012; 307(2):182-192 www.jama.com C1 [Yourman, Lindsey C.; Lee, Sei J.; Widera, Eric W.; Smith, Alexander K.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94121 USA. [Lee, Sei J.; Widera, Eric W.; Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Schonberg, Mara A.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Smith, AK (reprint author), Univ Calif San Francisco, Div Geriatr, Dept Med, 4150 Clement St 181G, San Francisco, CA 94121 USA. EM aksmith@ucsf.edu FU National Institute on Aging [5T32AG000212]; Greenwall Foundation; National Center for Research Resources [UL1 RR024131] FX Dr Yourman was supported by a National Institute on Aging T32 predoctoral fellowship position (5T32AG000212). Dr Smith was supported by career development grants from the Greenwall Foundation and the National Center for Research Resources to the Clinical and Translational Science Institute-University of California, San Francisco (UL1 RR024131). NR 74 TC 218 Z9 219 U1 6 U2 39 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 11 PY 2012 VL 307 IS 2 BP 182 EP 192 DI 10.1001/jama.2011.1966 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 875NP UT WOS:000299038300030 PM 22235089 ER PT J AU Scirica, BM Morrow, DA AF Scirica, Benjamin M. Morrow, David A. TI Potassium Concentration and Repletion in Patients With Acute Myocardial Infarction SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID VENTRICULAR-FIBRILLATION; SERUM POTASSIUM; HYPOKALEMIA; ARRHYTHMIAS; MAGNITUDE C1 [Scirica, Benjamin M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Levine Cardiac Unit,TIMI Study Grp,Cardiovasc Div, Boston, MA 02481 USA. RP Scirica, BM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Levine Cardiac Unit,TIMI Study Grp,Cardiovasc Div, 75 Francis St, Boston, MA 02481 USA. EM bscirica@partners.org NR 11 TC 6 Z9 6 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 11 PY 2012 VL 307 IS 2 BP 195 EP 196 DI 10.1001/jama.2011.2003 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 875NP UT WOS:000299038300032 PM 22235091 ER PT J AU Andronesi, OC Kim, GS Gerstner, E Batchelor, T Tzika, AA Fantin, VR Vander Heiden, MG Sorensen, AG AF Andronesi, Ovidiu C. Kim, Grace S. Gerstner, Elizabeth Batchelor, Tracy Tzika, Aria A. Fantin, Valeria R. Vander Heiden, Matthew G. Sorensen, A. Gregory TI Detection of 2-Hydroxyglutarate in IDH-Mutated Glioma Patients by In Vivo Spectral-Editing and 2D Correlation Magnetic Resonance Spectroscopy SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID H-1-NMR SPECTROSCOPY; WATER-SUPPRESSION; GENOMIC ANALYSIS; HR-MAS; MUTATIONS; H-1; GLIOBLASTOMA; ASTROCYTOMAS; METABOLITES; ACIDURIA AB Mutations in the gene isocitrate dehydrogenase 1 (IDH1) are present in up to 86% of grade II and III gliomas and secondary glioblastoma. Arginine 132 (R132) mutations in the enzyme IDH1 result in excess production of the metabolite 2-hydroxyglutarate (2HG), which could be used as a biomarker for this subset of gliomas. Here, we use optimized in vivo spectral-editing and two-dimensional (2D) correlation magnetic resonance spectroscopy (MRS) methods to unambiguously detect 2HG noninvasively in glioma patients with IDH1 mutations. By comparison, fitting of conventional 1D MR spectra can provide false-positive readouts owing to spectral overlap of 2HG and chemically similar brain metabolites, such as glutamate and glutamine. 2HG was also detected using 2D high-resolution magic angle spinning MRS performed ex vivo on a separate set of glioma biopsy samples. 2HG detection by in vivo or ex vivo MRS enabled detailed molecular characterization of a clinically important subset of human gliomas. This has implications for diagnosis as well as monitoring of treatments targeting mutated IDH1. C1 [Andronesi, Ovidiu C.; Kim, Grace S.; Tzika, Aria A.; Sorensen, A. Gregory] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Sch Med, Boston, MA 02114 USA. [Gerstner, Elizabeth; Batchelor, Tracy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pappas Ctr Neurooncol, Boston, MA 02114 USA. [Tzika, Aria A.] Massachusetts Gen Hosp, Dept Surg, NMR Surg Lab, Boston, MA 02114 USA. [Fantin, Valeria R.] Agios Pharmaceut, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tzika, Aria A.] Harvard Univ, Sch Med, Shriners Burn Inst, Boston, MA 02114 USA. RP Andronesi, OC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Sch Med, Boston, MA 02114 USA. EM ovidiu@nmr.mgh.harvard.edu OI /0000-0003-3210-2098 FU NIH [R01 1200-206456, S10RR013026, S10RR021110, S10RR023401]; Harvard Clinical and Translational Science Center (NIH) [KL2 RR 025757] FX This work was funded by grants from NIH (R01 1200-206456, S10RR013026, S10RR021110, and S10RR023401). O.C.A. was also supported by a KL2 Medical Research Investigator Training (MeRIT) award from Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH Award #KL2 RR 025757). NR 37 TC 69 Z9 69 U1 1 U2 21 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 JAN 11 PY 2012 VL 4 IS 116 AR 116ra4 DI 10.1126/scitranslmed.3002693 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 875DO UT WOS:000299010800003 PM 22238332 ER PT J AU Mayer, EL Gropper, AB Neville, BA Partridge, AH Cameron, DB Winer, EP Earle, CC AF Mayer, Erica L. Gropper, Adrienne B. Neville, Bridget A. Partridge, Ann H. Cameron, Danielle B. Winer, Eric P. Earle, Craig C. TI Breast Cancer Survivors' Perceptions of Survivorship Care Options SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GENERAL MEDICINE PRACTICE; ROUTINE FOLLOW-UP; RANDOMIZED-TRIAL; SPECIALIST CARE; VIRTUAL VISITS; PHYSICIANS; SATISFACTION; PROVIDERS; QUALITY; PATIENT AB Purpose As the number of breast cancer survivors increases, a durable model of comprehensive survivor care is needed, incorporating providers and/or visit types both within and outside of oncology. The objective of this study was to explore survivors' comfort with different clinician types or with a telephone/Internet-based virtual visit as components of survivorship care. Methods Breast cancer survivors participating in a general survivorship survey completed an additional breast cancer-specific questionnaire evaluating the self-perceived impact of follow-up visits to various clinician types, or follow-up by a virtual visit, on survival, worrying, and stress related to cancer. Results A total of 218 breast cancer survivors completed the questionnaire. Most favored medical oncologist follow-up visits over those with primary care physicians (PCPs) or nurse practitioners (NPs) in terms of reduced worrying about cancer (odds ratio [OR], 2.21; P < .001), reduced stress around the visit (OR, 1.40; P < .002), and improved effect on cancer survival (OR, 2.38; P < .001). However, the majority also displayed substantial comfort with both PCPs and NPs in the same domains. Patients rated a virtual visit as having a less favorable impact on cancer survival and cancer-related worrying compared with in-person visits with clinicians. Conclusion Breast cancer survivors are comfortable with both PCPs and NPs providing follow-up care, although they indicate a preference for medical oncologists. Given patients' negative impressions of a virtual visit, increased familiarity with and research investigating this emerging concept are needed. The NP-led survivorship clinic model, with increased guidance for PCPs, offers a promising route for improving quality of and satisfaction with survivor care. J Clin Oncol 30:158-163. (C) 2011 by American Society of Clinical Oncology C1 [Mayer, Erica L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gropper, Adrienne B.] Harvard Univ, Sch Med, Boston, MA USA. [Cameron, Danielle B.] Univ Miami, Miller Sch Med, Boca Raton, FL USA. [Earle, Craig C.] Inst Clin Evaluat Sci, Toronto, ON, Canada. RP Mayer, EL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM emayer@partners.org FU Perini Family Survivors' Center FX Supported by a grant from the Perini Family Survivors' Center. NR 37 TC 25 Z9 26 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2012 VL 30 IS 2 BP 158 EP 163 DI 10.1200/JCO.2011.36.9264 PG 6 WC Oncology SC Oncology GA 923KU UT WOS:000302619000016 PM 22162585 ER PT J AU Coumans, JVCE Walcott, BP Nahed, BV Oh, KS Chi, AS AF Coumans, Jean-Valery C. E. Walcott, Brian P. Nahed, Brian V. Oh, Kevin S. Chi, Andrew S. TI Multimodal Therapy of an Intramedullary Cervical Primitive Neuroectodermal Tumor in an Adult SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OF-THE-LITERATURE; SPINAL-CORD; CHILDREN; PNET C1 [Coumans, Jean-Valery C. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Coumans, JVCE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 20 TC 2 Z9 2 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 JAN 10 PY 2012 VL 30 IS 2 BP E15 EP E18 DI 10.1200/JCO.2011.38.6474 PG 4 WC Oncology SC Oncology GA 923KU UT WOS:000302619000004 PM 22147740 ER PT J AU Wu, ZW Zhang, XY Wang, HH Tang, W Xia, Y Zhang, FX Liu, JH Fu, Y Hu, JJ Chen, YL Liu, LJ Chen, DC Xiu, MH Kosten, TR He, JC AF Wu, Zhiwei Zhang, Xiang Yang Wang, Huanhuan Tang, Wei Xia, Yu Zhang, FeiXue Liu, Jiahong Fu, Ye Hu, Jianjun Chen, Yuanling Liu, Linjing Chen, Da Chun Xiu, Mei Hong Kosten, Thomas R. He, Jincai TI Elevated plasma superoxide dismutase in first-episode and drug naive patients with schizophrenia: Inverse association with positive symptoms SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE Free radical; Oxidative stress; Psychopathology; Schizophrenia; Superoxide dismutase ID ANTIOXIDANT DEFENSE SYSTEM; ACID REACTIVE SUBSTANCES; FREE-RADICAL PATHOLOGY; TARDIVE-DYSKINESIA; LIPID-PEROXIDATION; OXIDATIVE STRESS; ENZYME-ACTIVITIES; THERAPEUTIC IMPLICATIONS; ATYPICAL ANTIPSYCHOTICS; GLUTATHIONE-PEROXIDASE AB Excessive free radical production or oxidative stress may be involved in the pathophysiology of schizophrenia as evidenced by increased superoxide dismutase (SOD) activities, a critical enzyme in the detoxification of superoxide radicals. This study compared plasma SOD activities in 78 never-medicated first-episode and 100 medicated chronic schizophrenia patients to 100 healthy control subjects and correlated these SOD activities with the Positive and Negative Syndrome Scale (PANSS) among the schizophrenic patients. We found that both first-episode and chronic patients had significantly increased plasma SOD activities compared to controls, and that chronic schizophrenic patients on antipsychotic medication had significantly higher SOD activities than first episode schizophrenic patients. Plasma SOD activities were also negatively correlated with positive symptoms of schizophrenia, but only in first-episode patients. Thus, oxidative stress appears to be greater in first episode schizophrenic patients with fewer positive symptoms and may become greater as schizophrenia becomes more chronic, although we cannot exclude the possibility that chronic antipsychotic treatment may increase SOD activities and presumed oxidative stress in schizophrenia. (C) 2011 Elsevier Inc. All rights reserved. C1 [He, Jincai] Wenzhou Med Coll, Affiliated Hosp 1, Sleep Ctr, Wenzhou 325000, Peoples R China. [Zhang, Xiang Yang; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong] Beijing Huilongguan Hosp, Ctr Psychiat Res, Beijing, Peoples R China. [Wu, Zhiwei; Tang, Wei; Zhang, FeiXue; Liu, Jiahong; Chen, Yuanling; Liu, Linjing] Kangning Hosp, Dept Psychiat, Wenzhou, Peoples R China. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 110,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu; hjc@wzmc.edu.cn FU Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs; VISN 16; Mental Illness Research Education and Clinical Center (MIRECC); United States National Institute of Health [K05-DA0454, P50-DA18827, U01-MH79639] FX Funding for this study was provided by grants from the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. NR 52 TC 17 Z9 18 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 EI 1878-4216 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JAN 10 PY 2012 VL 36 IS 1 BP 34 EP 38 DI 10.1016/j.pnpbp.2011.08.018 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 889KQ UT WOS:000300073000007 PM 21896300 ER PT J AU Pai, S Ledoux, WR AF Pai, Shruti Ledoux, William R. TI The shear mechanical properties of diabetic and non-diabetic plantar soft tissue SO JOURNAL OF BIOMECHANICS LA English DT Article DE Foot; Diabetes; Subcutaneous; Ulceration; Viscoelastic ID BRAIN-TISSUE; VISCOELASTIC PROPERTIES; LARGE-DEFORMATION; HEEL-PAD; FAT PADS; FOOT; MELLITUS; CARTILAGE; STIFFNESS; PRESSURE AB Changes in the plantar soft tissue shear properties may contribute to ulceration in diabetic patients, however, little is known about these shear parameters. This study examines the elastic and viscoelastic shear behavior of both diabetic and non-diabetic plantar tissue. Previously compression tested plantar tissue specimens (n=54) at six relevant plantar locations (hallux, first, third, and fifth metatarsal heads, lateral midfoot, and calcaneus) from four cadaveric diabetic feet and five non-diabetic feet were utilized. Per in vivo data (i.e., combined deformation patterns of compression followed by shear), an initial static compressive strain (36-38%) was applied to the tissue followed by target shear strains of 50% and 85% of initial thickness. Triangle waves were used to quantify elastic parameters at both strain levels and a stress relaxation test (0.25 s ramp and 300 s hold) was used to quantify the viscoelastic parameters at the upper strain level. Several differences were found between test groups including a 52-62% increase in peak shear stress, a 63% increase in toe shear modulus, a 47% increase in final shear modulus, and a 67% increase in middle slope magnitude (sharper drop in relaxation) in the diabetic tissue. Beyond a 54% greater peak compressive stress in the third metatarsal compared to the lateral midfoot, there were no differences in shear properties between plantar locations. Notably, this study demonstrates that plantar soft tissue with diabetes is stiffer than healthy tissue, thereby compromising its ability to dissipate shear stresses borne by the foot that may increase ulceration risk. Published by Elsevier Ltd. C1 [Pai, Shruti; Ledoux, William R.] VA Puget Sound, VA RR&D Ctr Excellence Limb Loss Prevent & Prosth, Seattle, WA 98108 USA. [Pai, Shruti; Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Ledoux, William R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound, VA RR&D Ctr Excellence Limb Loss Prevent & Prosth, MS 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU National Institutes of Health [1R01 DK75633-03]; Department of Veterans Affairs, RRD Service [A4843C] FX This study was supported by the National Institutes of Health grant 1R01 DK75633-03 and the Department of Veterans Affairs, RR&D Service grant A4843C. The authors would also like to thank Jane Shofer for the statistical analysis, Michael Fassbind for equipment design, and Paul Vawter for assisting with data analysis. NR 39 TC 14 Z9 14 U1 1 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD JAN 10 PY 2012 VL 45 IS 2 BP 364 EP 370 DI 10.1016/j.jbiomech.2011.10.021 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 885BX UT WOS:000299754600023 PM 22079385 ER PT J AU Wang, TY Masoudi, FA Messenger, JC Shunk, KA Boyle, A Brennan, JM Anderson, HV Anstrom, KJ Dai, D Peterson, ED Douglas, PS Rumsfeld, JS AF Wang, Tracy Y. Masoudi, Frederick A. Messenger, John C. Shunk, Kendrick A. Boyle, Andrew Brennan, J. Matthew Anderson, H. Vernon Anstrom, Kevin J. Dai, David Peterson, Eric D. Douglas, Pamela S. Rumsfeld, John S. TI Percutaneous Coronary Intervention and Drug-Eluting Stent Use Among Patients >= 85 Years of Age in the United States SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE aging; coronary artery disease; myocardial infarction; stent ID PREDICTS COGNITIVE DECLINE; LONGER HOSPITAL STAY; BARE-METAL STENTS; ELDERLY-PATIENTS; CARDIAC-SURGERY; OUTCOMES; REGISTRY; TRIALS AB Objectives This study assessed the comparative effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) among patients >= 85 years of age. Background Despite an aging population, little is known about the comparative effectiveness of DES versus BMS among patients age >= 85 years undergoing percutaneous coronary intervention (PCI). Methods We examined 471,006 PCI patients age >= 65 years at 947 hospitals in the National Cardiovascular Data Registry between 2004 and 2008 and linked to Medicare claims data. Long-term outcomes (median follow-up 640.8 +/- 423.5 days) were compared between users of DES and BMS. Results Patients age >= 85 years comprise an increasing proportion of PCIs performed among elderly subjects, yet rates of DES use declined the most in this age group. Compared with BMS, use of DES was associated with lower mortality: age >85 years, 29% versus 38% (adjusted hazard ratio [HR]: 0.80 [95% confidence interval (CI): 0.77 to 0.83]); age 75 to 84 years, 17% versus 25% (HR: 0.77 [95% CI: 0.75 to 0.79]); and age 65 to 74 years, 10% versus 16% (HR: 0.73 [95% CI: 0.71 to 0.75]). However, the adjusted mortality difference narrowed with increasing age (p(interaction) <0.001). In contrast, the adjusted HR for myocardial infarction rehospitalization associated with DES use was significantly lower with increasing age: age >= 85 years, 9% versus 12% (HR: 0.77 [95% CI: 0.71 to 0.83]); age 75 to 84 years, 7% versus 9% (HR: 0.81 [95% CI: 0.77 to 0.84]); and age 65 to 74 years, 7% versus 8% (HR: 0.84 [95% CI: 0.80 to 0.88]) (p(interaction) <0.001). Conclusions In this national study of older patients undergoing PCI, declines in DES use were most pronounced among those aged >= 85 years, yet lower adverse-event rates associated with DES versus BMS use were observed. (J Am Coll Cardiol 2012; 59: 105-12) (C) 2012 by the American College of Cardiology Foundation C1 [Wang, Tracy Y.; Brennan, J. Matthew; Anstrom, Kevin J.; Dai, David; Peterson, Eric D.; Douglas, Pamela S.] Duke Clin Res Inst, Durham, NC 27705 USA. [Masoudi, Frederick A.; Messenger, John C.] Univ Colorado, Aurora, CO USA. [Shunk, Kendrick A.; Boyle, Andrew] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Anderson, H. Vernon] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. RP Wang, TY (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA. EM tracy.wang@duke.edu OI Boyle, Andrew/0000-0002-3919-5269 FU Agency for Healthcare Research and Quality; U.S. Department of Health and Human Services [24-EHC-1, HHSAA290-2005-0032-TO4-WA1]; Bristol-Myers Squibb/Sanofi Aventis; Schering-Plough/Merck Co., Inc.; Medicines Company; Heartscape Technologies, Inc.; Canyon Pharmaceuticals; Eli Lilly and Company/Daiichi Sankyo alliance; American College of Cardiology; Alexion Pharmaceuticals; AstraZeneca; Bristol-Myers Squibb; Eli Lilly and Company; Innocoll Pharmaceuticals; Medtronic; Pfizer Inc.; Proctor & Gamble (modest); Merck Co., Inc.; Johnson Johnson FX This project was sponsored by the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, as part of the Cardiovascular Consortium (Project ID: 24-EHC-1, Work Assignment Number: HHSAA290-2005-0032-TO4-WA1, Developing Evidence to Inform Decisions about Effectiveness program). The authors of this paper are responsible for its content, and statements in the paper should not be construed as endorsement by the Agency for Healthcare Research and Quality or the Department of Health and Human Services. Additional support was obtained from the American College of Cardiology National Cardiovascular Data Registry. Dr. Wang has received research grants (to the Duke Clinical Research Institute) from Bristol-Myers Squibb/Sanofi Aventis Partnership, Schering-Plough/Merck & Co., Inc., The Medicines Company, Heartscape Technologies, Inc., Canyon Pharmaceuticals, and Eli Lilly and Company/Daiichi Sankyo alliance; and consulting or honoraria from Medco Health Solutions, Inc., and AstraZeneca. Dr. Masoudi has received salary support from the American College of Cardiology; is senior medical officer for the National Cardiovascular Data Registry (significant); and is a consultant for the Oklahoma Foundation for Medical Quality. Dr. Anstrom has received research and salary support from Alexion Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Innocoll Pharmaceuticals, Medtronic, Pfizer Inc., and Proctor & Gamble (modest); serves on the data safety monitoring boards of Pfizer Inc. and Vertex Pharmaceuticals (modest); and provides consulting services to Pacific Therapeutics Ltd., Bristol-Myers Squibb, and AstraZeneca (modest). Dr. Peterson has received research support from Bristol-Myers Squibb/Sanofi Aventis Partnership, Merck & Co., Inc., Johnson & Johnson, and Eli Lilly and Company (all significant). Dr. Rumsfeld is the chief science officer for the National Cardiovascular Data Registry. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 16 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 10 PY 2012 VL 59 IS 2 BP 105 EP 112 DI 10.1016/j.jacc.2011.10.853 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 872GH UT WOS:000298796600003 PM 22222072 ER PT J AU Lee, WW Marinelli, B van der Laan, AM Sena, BF Gorbatov, R Leuschner, F Dutta, P Iwamoto, Y Ueno, T Begieneman, MPV Niessen, HWM Piek, JJ Vinegoni, C Pittet, MJ Swirski, FK Tawakol, A Di Carli, M Weissleder, R Nahrendorf, M AF Lee, Won Woo Marinelli, Brett van der Laan, Anja M. Sena, Brena F. Gorbatov, Rostic Leuschner, Florian Dutta, Partha Iwamoto, Yoshiko Ueno, Takuya Begieneman, Mark P. V. Niessen, Hans W. M. Piek, Jan J. Vinegoni, Claudio Pittet, Mikael J. Swirski, Filip K. Tawakol, Ahmed Di Carli, Marcelo Weissleder, Ralph Nahrendorf, Matthias TI PET/MRI of Inflammation in Myocardial Infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE inflammation; myocardial infarction; PET/MRI; remote myocardium ID CARDIOVASCULAR MAGNETIC-RESONANCE; CORONARY-ARTERIES; SPLENIC RESERVOIR; MONOCYTE SUBSETS; MICE; ATHEROSCLEROSIS; METABOLISM; DISEASE AB Objectives The aim of this study was to explore post-myocardial infarction (MI) myocardial inflammation. Background Innate immune cells are centrally involved in infarct healing and are emerging therapeutic targets in cardiovascular disease; however, clinical tools to assess their presence in tissue are scarce. Furthermore, it is currently not known if the nonischemic remote zone recruits monocytes. Methods Acute inflammation was followed in mice with coronary ligation by 18-fluorodeoxyglucose ((18)FDG) positron emission tomography/magnetic resonance imaging, fluorescence-activated cell sorting, polymerase chain reaction, and histology. Results Gd-DTPA-enhanced infarcts showed high (18)FDG uptake on day 5 after MI. Cell depletion and isolation data confirmed that this largely reflected inflammation; CD11b(+) cells had 4-fold higher (18)FDG uptake than the infarct tissue from which they were isolated (p < 0.01). Surprisingly, there was considerable monocyte recruitment in the remote myocardium (approximately 10(4)/mg of myocardium, 5.6-fold increase; p < 0.01), a finding mirrored by macrophage infiltration in the remote myocardium of patients with acute MI. Temporal kinetics of cell recruitment were slower than in the infarct, with peak numbers on day 10 after ischemia. Quantitative polymerase chain reaction showed a robust increase of recruiting adhesion molecules and chemokines in the remote myocardium (e.g., 12-fold increase of monocyte chemoattractant protein-1), although levels were always lower than in the infarct. Finally, matrix metalloproteinase activity was significantly increased in noninfarcted myocardium, suggesting that monocyte recruitment to the remote zone may contribute to post-MI dilation. Conclusions This study shed light on the innate inflammatory response in remote myocardium after MI. (J Am Coll Cardiol 2012; 59: 153-63) (C) 2012 by the American College of Cardiology Foundation C1 [Lee, Won Woo; Marinelli, Brett; Sena, Brena F.; Gorbatov, Rostic; Leuschner, Florian; Dutta, Partha; Iwamoto, Yoshiko; Ueno, Takuya; Vinegoni, Claudio; Pittet, Mikael J.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Lee, Won Woo; Marinelli, Brett; Sena, Brena F.; Gorbatov, Rostic; Leuschner, Florian; Dutta, Partha; Iwamoto, Yoshiko; Ueno, Takuya; Vinegoni, Claudio; Pittet, Mikael J.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Won Woo] Seoul Natl Univ, Coll Med, Dept Nucl Med, Bundang Hosp, Seoul, South Korea. [van der Laan, Anja M.; Piek, Jan J.] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands. [Begieneman, Mark P. V.; Niessen, Hans W. M.] Vrije Univ Amsterdam Med Ctr, Dept Pathol & Cardiac Surg, ICaR VU, Amsterdam, Netherlands. [Tawakol, Ahmed] Massachusetts Gen Hosp, Div Cardiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Tawakol, Ahmed] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Di Carli, Marcelo] Brigham & Womens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. RP Nahrendorf, M (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu RI Lee, Won Woo/J-5589-2012; Library, JinyoungPark/F-3767-2011 OI Library, JinyoungPark/0000-0003-0952-1374 FU National Institutes of Health [R01HL095629, R01HL096576, HHSN268201000044C, RO1EB006432, R24-CA92782]; Korea Research Foundation [KRF-2009-013-E00027] FX This work was funded in parts by grants from the National Institutes of Health (R01HL095629 and R01HL096576 to Dr. Nahrendorf, Translational Program of Excellence in Nanotechnology HHSN268201000044C, RO1EB006432, R24-CA92782 to Dr. Weissleder), AHA Scientist Development Grant to Dr. Nahrendorf, Korea Research Foundation Grant (KRF-2009-013-E00027) to Dr. Lee, and Deutsche Herzstiftung e. V. to Dr. Leuschner. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The first two authors contributed equally to this work. NR 34 TC 113 Z9 116 U1 6 U2 25 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 JAN 10 PY 2012 VL 59 IS 2 BP 153 EP 163 DI 10.1016/j.jacc.2011.08.066 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 872GH UT WOS:000298796600011 PM 22222080 ER PT J AU Brown, KH Dobrinski, KP Lee, AS Gokcumen, O Mills, RE Shi, XH Chong, WWS Chen, JYH Yoo, P David, S Peterson, SM Raj, T Choy, KW Stranger, BE Williamson, RE Zon, LI Freeman, JL Lee, C AF Brown, Kim H. Dobrinski, Kimberly P. Lee, Arthur S. Gokcumen, Omer Mills, Ryan E. Shi, Xinghua Chong, Wilson W. S. Chen, Jin Yun Helen Yoo, Paulo David, Sthuthi Peterson, Samuel M. Raj, Towfique Choy, Kwong Wai Stranger, Barbara E. Williamson, Robin E. Zon, Leonard I. Freeman, Jennifer L. Lee, Charles TI Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE comparative genomic hybridization; structural variation; gene expression ID HUMAN-DISEASE; HUMAN GENOME; CONSERVATION GENETICS; DANIO-RERIO; POLYMORPHISM; EXPRESSION; ADMIXTURE; SELECTION; MOUSE AB Copy number variants (CNVs) represent a substantial source of genomic variation in vertebrates and have been associated with numerous human diseases. Despite this, the extent of CNVs in the zebrafish, an important model for human disease, remains unknown. Using 80 zebrafish genomes, representing three commonly used laboratory strains and one native population, we constructed a genome-wide, high-resolution CNV map for the zebrafish comprising 6,080 CNV elements and encompassing 14.6% of the zebrafish reference genome. This amount of copy number variation is four times that previously observed in other vertebrates, including humans. Moreover, 69% of the CNV elements exhibited strain specificity, with the highest number observed for Tubingen. This variation likely arose, in part, from Tubingen's large founding size and composite population origin. Additional population genetic studies also provided important insight into the origins and substructure of these commonly used laboratory strains. This extensive variation among and within zebrafish strains may have functional effects that impact phenotype and, if not properly addressed, such extensive levels of germ-line variation and population substructure in this commonly used model organism can potentially confound studies intended for translation to human diseases. C1 [Brown, Kim H.; Dobrinski, Kimberly P.; Lee, Arthur S.; Gokcumen, Omer; Mills, Ryan E.; Shi, Xinghua; Chong, Wilson W. S.; Chen, Jin Yun Helen; Yoo, Paulo; David, Sthuthi; Freeman, Jennifer L.; Lee, Charles] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Brown, Kim H.; Dobrinski, Kimberly P.; Gokcumen, Omer; Mills, Ryan E.; Shi, Xinghua; Raj, Towfique; Stranger, Barbara E.; Freeman, Jennifer L.; Lee, Charles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chong, Wilson W. S.; Choy, Kwong Wai] Chinese Univ Hong Kong, Dept Obstet & Gynaecol, Hong Kong, Hong Kong, Peoples R China. [Peterson, Samuel M.] Purdue Univ, Sch Hlth Sci, W Lafayette, IN 47907 USA. [Raj, Towfique; Stranger, Barbara E.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Raj, Towfique; Stranger, Barbara E.; Lee, Charles] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Raj, Towfique] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Williamson, Robin E.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Harvard Stem Cell Inst, Dana Farber Canc Inst, Howard Hughes Med Inst,Sch Med, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Lee, C (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM clee@rics.bwh.harvard.edu RI Mills, Ryan/A-1979-2011; OI Mills, Ryan/0000-0003-3425-6998; Gokcumen, Omer/0000-0003-4371-679X; Stranger, Barbara/0000-0001-9021-7331 FU Department of Pathology, Brigham and Women's Hospital; National Institutes of Health (NIH)-National Heart, Lung, and Blood Institute [T32HL007627]; NIH-National Institute of Environmental Health Sciences [1K99ES018892]; Hong Kong General Research Fund; NIH-National Cancer Institute [5R01CA111560]; NIH-National Human Genome Research Institute [5P41HG004421] FX We thank S. Stephen and J. Mattick for UCE chromosome locations; Agilent Technologies for zebrafish HD probe sequences; M. Gutierrez-Arcelus, C. Ihm, C. Tran, and I. Smolina for technical assistance; J. Dobrinski for assistance with Figs. 1 and 3; and G. Paull, N. Trede, K. Frazer, T. Look, and C. Tyler for fish. Research was supported by an Institutional National Research Service Award Fellowship (to K. H. B.) from Department of Pathology, Brigham and Women's Hospital and by Grant T32HL007627 [National Institutes of Health (NIH)-National Heart, Lung, and Blood Institute]; Grant 1K99ES018892 (NIH-National Institute of Environmental Health Sciences) (to K. H. B.); Hong Kong General Research Fund (to K. W. C.); and Grants 5R01CA111560 (NIH-National Cancer Institute) and 5P41HG004421 (NIH-National Human Genome Research Institute) (to C. L.). NR 42 TC 31 Z9 31 U1 0 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 10 PY 2012 VL 109 IS 2 BP 529 EP 534 DI 10.1073/pnas.1112163109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 874IS UT WOS:000298950200041 PM 22203992 ER PT J AU Jacob, CO Eisenstein, M Dinauer, MC Ming, WY Liu, Q John, S Quismorio, FP Reiff, A Myones, BL Kaufman, KM McCurdy, D Harley, JB Silverman, E Kimberly, RP Vyse, TJ Gaffney, PM Moser, KL Klein-Gitelman, M Wagner-Weiner, L Langefeld, CD Armstrong, DL Zidovetzki, R AF Jacob, Chaim O. Eisenstein, Miriam Dinauer, Mary C. Ming, Wenyu Liu, Qiang John, Sutha Quismorio, Francesco P., Jr. Reiff, Andreas Myones, Barry L. Kaufman, Kenneth M. McCurdy, Deborah Harley, John B. Silverman, Earl Kimberly, Robert P. Vyse, Timothy J. Gaffney, Patrick M. Moser, Kathy L. Klein-Gitelman, Marisa Wagner-Weiner, Linda Langefeld, Carl D. Armstrong, Don L. Zidovetzki, Raphael TI Lupus-associated causal mutation in neutrophil cytosolic factor 2 (NCF2) brings unique insights to the structure and function of NADPH oxidase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; NOX2 ID CHRONIC GRANULOMATOUS-DISEASE; PROTEIN-PROTEIN DOCKING; GENOME-WIDE ASSOCIATION; CONTROLS PHAGOSOMAL PH; AUTOIMMUNE-DISEASE; OXIDATIVE BURST; DENDRITIC CELLS; ERYTHEMATOSUS; SUSCEPTIBILITY; GENE AB Systemic lupus erythematosus (SLE), the prototypic systemic autoimmune disease, is a debilitating multisystem autoimmune disorder characterized by chronic inflammation and extensive immune dysregulation in multiple organ systems, resulting in significant morbidity and mortality. Here, we present a multidisciplinary approach resulting in the identification of neutrophil cytosolic factor 2 (NCF2) as an important risk factor for SLE and the detailed characterization of its causal variant. We show that NCF2 is strongly associated with increased SLE risk in two independent populations: childhood-onset SLE and adult-onset SLE. The association between NCF2 and SLE can be attributed to a single nonsynonymous coding mutation in exon 12, the effect of which is the substitution of histidine-389 with glutamine (H389Q) in the PB1 domain of the NCF2 protein, with glutamine being the risk allele. Computational modeling suggests that the NCF2 H389Q mutation reduces the binding efficiency of NCF2 with the guanine nucleotide exchange factor Vav1. The model predicts that NCF2/H389 residue interacts with Vav1 residues E509, N510, E556, and G559 in the ZF domain of Vav1. Furthermore, replacing H389 with Q results in 1.5 kcal/mol weaker binding. To examine the effect of the NCF2 H389Q mutation on NADPH oxidase function, site-specific mutations at the 389 position in NCF2 were tested. Results show that an H389Q mutation causes a twofold decrease in reactive oxygen species production induced by the activation of the Vav-dependent Fc. receptor-elicited NADPH oxidase activity. Our study completes the chain of evidence from genetic association to specific molecular function. C1 [Jacob, Chaim O.; Quismorio, Francesco P., Jr.; Reiff, Andreas; Zidovetzki, Raphael] Univ So Calif, Dept Med, Lupus Genet Grp, Los Angeles, CA 90089 USA. [Eisenstein, Miriam] Weizmann Inst Sci, Dept Chem Res Support, IL-76100 Rehovot, Israel. [Dinauer, Mary C.; Liu, Qiang] Washington Univ, St Louis Childrens Hosp, Sch Med, St Louis, MO 63110 USA. [Ming, Wenyu; John, Sutha] Indiana Univ Sch Med, Dept Pediat, Wells Ctr Pediat Res, Indianapolis, IN 46202 USA. [Reiff, Andreas] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Myones, Barry L.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Kaufman, Kenneth M.; Gaffney, Patrick M.; Moser, Kathy L.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [McCurdy, Deborah] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA. [Harley, John B.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH 45229 USA. [Silverman, Earl] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Kimberly, Robert P.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Vyse, Timothy J.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London W12 0NN, England. [Klein-Gitelman, Marisa] Childrens Mem Hosp, Chicago, IL 60614 USA. [Klein-Gitelman, Marisa] Northwestern Univ, Chicago, IL 60614 USA. [Wagner-Weiner, Linda] LaRabida Hosp, Chicago, IL 60649 USA. [Wagner-Weiner, Linda] Univ Chicago, Chicago, IL 60649 USA. [Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Winston Salem, NC 27157 USA. [Armstrong, Don L.; Zidovetzki, Raphael] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. RP Jacob, CO (reprint author), Univ So Calif, Dept Med, Lupus Genet Grp, Los Angeles, CA 90089 USA. EM jacob@usc.edu; raphael.zidovetzki@ucr.edu OI Armstrong, Don/0000-0002-4904-638X; Kimberly, Robert/0000-0002-5330-3086 FU National Institutes of Health [AR043815, HL45635, AR62277, AI08394, AI024717, AR042460, AR049084, AR33062, RR020143, AI063274] FX We thank Y.X. Wu for technical assistance, C. Marchal and M. Stefanovic for assistance with generating some of the NCF2 expression constructs, J. Matute and X. Li for generating the transgenic K562 cell line, and Dr. XingPing Cui for fruitful discussions. Support for this study was provided by National Institutes of Health Grants AR043815 (to C.O.J.); HL45635 (to M.C.D.); AR62277 (to K.L.M.); AI08394, AI024717, AR042460 (to J.B.H.); AR049084 and AR33062 (to R.P.K.); and RR020143 and AI063274 (to P.M.G.). Additional support was provided by the Alliance for Lupus Research (C.O.J., J.B.H., and R.Z.), Riley Children's Foundation (M.C.D.), Children's Discovery Institute (M.C.D.), and US Department of Veterans Affairs Medical Center, Cincinnati (J.B.H.). NR 49 TC 53 Z9 53 U1 0 U2 7 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 JAN 10 PY 2012 VL 109 IS 2 BP E59 EP E67 DI 10.1073/pnas.1113251108 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 874IS UT WOS:000298950200006 PM 22203994 ER PT J AU Yu, YM Zhu, JH Mi, LZ Walz, T Sun, H Chen, JF Springer, TA AF Yu, Yamei Zhu, Jianghai Mi, Li-Zhi Walz, Thomas Sun, Hao Chen, JianFeng Springer, Timothy A. TI Structural specializations of alpha(4)beta(7), an integrin that mediates rolling adhesion SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CRYSTAL-STRUCTURE; BINDING-SITES; MONOCLONAL-ANTIBODY; HUMANIZED ANTIBODY; ALPHA-4 INTEGRIN; LIGAND-BINDING; CROHNS-DISEASE; HYBRID DOMAIN; ACTIVATION; MOLECULE-1 AB The lymphocyte homing receptor integrin alpha(4)beta(7) is unusual for its ability to mediate both rolling and firm adhesion. alpha(4)beta(1) and alpha(4)beta(7) are targeted by therapeutics approved for multiple sclerosis and Crohn's disease. Here, we show by electron microscopy and crystallography how two therapeutic Fabs, a small molecule (RO0505376), and mucosal adhesion molecule-1 (MAdCAM-1) bind alpha(4)beta(7). A long binding groove at the alpha(4)-beta(7) interface for immunoglobulin superfamily domains differs in shape from integrin pockets that bind Arg-Gly-Asp motifs. RO0505376 mimics an Ile/Leu-Asp motif in alpha(4) ligands, and orients differently from Arg-Gly-Asp mimics. A novel auxiliary residue at the metal iondependent adhesion site in alpha(4)beta(7) is essential for binding to MAdCAM-1 in Mg2+ yet swings away when RO0505376 binds. A novel intermediate conformation of the alpha(4)beta(7) headpiece binds MAdCAM-1 and supports rolling adhesion. Lack of induction of the open headpiece conformation by ligand binding enables rolling adhesion to persist until integrin activation is signaled. C1 [Yu, Yamei; Zhu, Jianghai; Mi, Li-Zhi; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Immune Dis Inst, Boston, MA 02115 USA. [Yu, Yamei; Zhu, Jianghai; Mi, Li-Zhi; Springer, Timothy A.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Sun, Hao; Chen, JianFeng] Chinese Acad Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Immune Dis Inst, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI Zhu, Jianghai/B-7339-2014; Mi, Li-Zhi/B-1371-2016 OI Mi, Li-Zhi/0000-0001-9907-5245 FU National Institutes of Health [HL48675]; HHMI FX This paper was supported by National Institutes of Health grant HL48675 and HHMI. NR 68 TC 30 Z9 32 U1 2 U2 17 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 9 PY 2012 VL 196 IS 1 BP 131 EP 146 DI 10.1083/jcb.201110023 PG 16 WC Cell Biology SC Cell Biology GA 878PM UT WOS:000299269000012 PM 22232704 ER PT J AU Lin, E Bhusal, Y Horwitz, D Shelburne, SA Trautner, BW AF Lin, Eugene Bhusal, Yogesh Horwitz, Deborah Shelburne, Samuel A., III Trautner, Barbara W. TI Overtreatment of Enterococcal Bacteriuria SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID URINARY-TRACT-INFECTIONS; VANCOMYCIN-RESISTANT ENTEROCOCCI; CLINICAL-PRACTICE GUIDELINES; CARE-ASSOCIATED INFECTIONS; ASYMPTOMATIC BACTERIURIA; RISK-FACTORS; INAPPROPRIATE TREATMENT; DISEASES-SOCIETY; ADULTS; BACTEREMIA AB Background: The purposes of this study were to investigate the clinical outcomes of enterococcal bacteriuria and to determine whether current management is adherent to Infectious Diseases Society of America guidelines. Methods: We conducted a retrospective medical record review of patients from 2 academic teaching hospitals for 3 months (September 1 through November 30, 2009). Patients were classified as having urinary tract infection (UTI) or asymptomatic bacteriuria (ABU) by applying the guidelines. Antibiotic use was deemed appropriate in patients with UTI and inappropriate in ABU. Medical records were reviewed for Enterococcus cultured from another sterile site within 30 days. Results: A total of 375 urine cultures growing Enterococcus were reviewed, with 339 cultures meeting inclusion criteria. Of these 339 episodes, 183 (54.0%) were classified as ABU and 156 (46.0%) as UTI. In 289 episodes accompanied by urinalysis, pyuria was associated with UTI in 98 of 140 episodes (70.0%) compared with 63 of 149 episodes of ABU (42.3%) (odds ratio, 3.19; 95% CI, 1.96-5.18). Providers inappropriately treated 60 of 183 episodes of ABU (32.8%) with antibiotics. In multivariate analysis, only pyuria was associated with the inappropriate use of antibiotics (odds ratio, 3.27; 95% CI, 1.49-7.18). Only 7 subsequent infections with Enterococcus occurred in the 339 episodes of bacteriuria overall (2.1%), with 2 of the 183 cases of ABU (1.1%) having distant infection. Conclusions: Providers often overtreat enterococcal ABU with antibiotics, particularly in patients with pyuria. Given the low incidence of infectious complications, efforts should be made to optimize the use of antibiotics in enterococcal bacteriuria. C1 [Lin, Eugene; Bhusal, Yogesh; Horwitz, Deborah; Trautner, Barbara W.] Baylor Coll Med, Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect,Dept Med, Houston, TX 77030 USA. [Trautner, Barbara W.] Baylor Coll Med, Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Michael E DeBakey Vet Affairs Med Ctr, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Shelburne, Samuel A., III] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA. RP Trautner, BW (reprint author), Baylor Coll Med, Houston Vet Affairs Hlth Serv Res & Dev Ctr Excel, Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect,Dept Med, Mail Stop 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM trautner@bcm.edu FU Veterans Affairs Career Development Award [B4623]; Health Services Research & Development Service [IIR 09-104]; Houston Veterans Affairs Health Services Research & Development Service Center of Excellence [HFP90-020] FX Dr Trautner's work was supported by a Veterans Affairs Career Development Award (B4623) and by Health Services Research & Development Service IIR 09-104. This work was supported in part by the Houston Veterans Affairs Health Services Research & Development Service Center of Excellence (HFP90-020). NR 33 TC 30 Z9 31 U1 0 U2 3 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 JAN 9 PY 2012 VL 172 IS 1 BP 33 EP 38 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 874LM UT WOS:000298958900006 PM 22232145 ER PT J AU Peralta, CA Norris, KC Li, SY Chang, TI Tamura, MK Jolly, SE Bakris, G McCullough, PA Shlipak, M AF Peralta, Carmen A. Norris, Keith C. Li, Suying Chang, Tara I. Tamura, Manjula K. Jolly, Stacey E. Bakris, George McCullough, Peter A. Shlipak, Michael CA KEEP Investigators TI Blood Pressure Components and End-stage Renal Disease in Persons With Chronic Kidney Disease The Kidney Early Evaluation Program (KEEP) SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DIABETIC-NEPHROPATHY; AFRICAN-AMERICAN; FOLLOW-UP; PROGRESSION; RISK; HYPERTENSION; PROTEINURIA; MICROALBUMINURIA; POPULATION; TARGET AB Background: Treatment of hypertension is difficult in chronic kidney disease (CKD), and blood pressure goals remain controversial. The association between each blood pressure component and end-stage renal disease (ESRD) risk is less well known. Methods: We studied associations of systolic and diastolic blood pressure (SBP and DBP, respectively) and pulse pressure (PP) with ESRD risk among 16 129 Kidney Early Evaluation Program (KEEP) participants with an estimated glomerular filtration rate of 60 mL/min/1.73 m(2) using Cox proportional hazards. We estimated the prevalence and characteristics associated with uncontrolled hypertension (SBP >= 150 or DBP >= 90 mm Hg). Results: The mean (SD) age of participants was 69 (12) years; 25% were black, 6% were Hispanic, and 43% had diabetes mellitus. Over 2.87 years, there were 320 ESRD events. Higher SBP was associated with higher ESRD risk, starting at SBP of 140 mm Hg or higher. After sex and age adjustment, compared with SBP lower than 130 mm Hg, hazard ratios (HRs) were 1.08 (95% CI, 0.74-1.59) for SBP of 130 to 139 mm Hg, 1.72 (95% CI, 1.21-2.45) for SBP of 140 to 149 mm Hg, and 3.36 (95% CI, 2.51-4.49) for SBP of 150 mm Hg or greater. After full adjustment, HRs for ESRD were 1.27 (95% CI, 0.88-1.83) for SBP of 140 to 149 mm Hg and 1.36 (95% CI, 1.02-1.85) for SBP of 150 mm Hg or higher. Persons with DBP of 90 mm Hg or higher were at higher risk for ESRD compared with persons with DBP of 60 to 74 mm Hg (HR, 1.81; 95% CI, 1.33-2.45). Higher PP was also associated with higher ESRD risk (HR, 1.44 [95% CI, 1.00-2.07] for PP >= 80 mm Hg compared with PP < 50 mm Hg). Adjustment for SBP attenuated this association. More than 33% of participants had uncontrolled hypertension (SBP >= 150 mm Hg or DBP >= 90 mm Hg), mostly due to isolated systolic hypertension (54%). Conclusions: In this large, diverse, community-based sample, we found that high SBP seemed to account for most of the risk of progression to ESRD. This risk started at SBP of 140 mm Hg rather than the currently recommended goal of less than 130 mm Hg, and it was highest among those with SBP of at least 150 mm Hg. Treatment strategies that preferentially lower SBP may be required to improve BP control in CKD. C1 [Peralta, Carmen A.; Shlipak, Michael] Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. [Peralta, Carmen A.; Shlipak, Michael] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Norris, Keith C.] Charles Drew Univ Med & Sci, Dept Internal Med, Los Angeles, CA USA. [Li, Suying] Minneapolis Med Res Fdn Inc, Chron Dis Res Grp, Minneapolis, MN USA. [Chang, Tara I.; Tamura, Manjula K.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Jolly, Stacey E.] Cleveland Clin, Dept Gen Internal Med, Inst Med, Cleveland, OH 44106 USA. [Bakris, George] Univ Chicago, Pritzker Sch Med, Hypertens Dis Unit, Chicago, IL 60637 USA. [McCullough, Peter A.] Providence Pk Heart Inst, Dept Med, St John Providence Hlth Syst, Novi, MI USA. RP Peralta, CA (reprint author), Univ Calif San Francisco, Dept Med, 4150 Clement St,111A1, San Francisco, CA 94121 USA. EM carmenalicia.peralta@ucsf.edu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU National Institute of Diabetes and Digestive and Kidney Diseases [1K23SK082793]; Robert Wood Johnson Harold Amos award; National Institutes of Health [MD00148, 1U54RR026138]; Amgen; Abbott; Novartis; Siemens; Genentech; Genzyme; Nephroceuticals; Pfizer; LifeScan; Suplena FX Dr Peralta is funded by National Institute of Diabetes and Digestive and Kidney Diseases grant 1K23SK082793 and a Robert Wood Johnson Harold Amos award. Dr Norris is supported by National Institutes of Health grants MD00148 and 1U54RR026138. KEEP is a program of the National Kidney Foundation and is supported by Amgen, Abbott, Novartis, Siemens, Genentech, Genzyme, Nephroceuticals, Pfizer, LifeScan, and Suplena. NR 29 TC 55 Z9 58 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 JAN 9 PY 2012 VL 172 IS 1 BP 41 EP 47 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 874LM UT WOS:000298958900008 PM 22232147 ER PT J AU Smith, MR Saad, F Coleman, R Shore, N Fizazi, K Tombal, B Miller, K Sieber, P Karsh, L Damiao, R Tammela, TL Egerdie, B Van Poppel, H Chin, J Morote, J Gomez-Veiga, F Borkowski, T Ye, ZS Kupic, A Dansey, R Goessl, C AF Smith, Matthew R. Saad, Fred Coleman, Robert Shore, Neal Fizazi, Karim Tombal, Bertrand Miller, Kurt Sieber, Paul Karsh, Lawrence Damiao, Ronaldo Tammela, Teuvo L. Egerdie, Blair Van Poppel, Hendrik Chin, Joseph Morote, Juan Gomez-Veiga, Francisco Borkowski, Tomasz Ye, Zhishen Kupic, Amy Dansey, Roger Goessl, Carsten TI Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial SO LANCET LA English DT Article ID SKELETAL-RELATED EVENTS; OSTEOPROTEGERIN LIGAND; ANDROGEN DEPRIVATION; ZOLEDRONIC ACID; BREAST-CANCER; COMPLICATIONS; ACTIVATION; DISEASE AB Background Bone metastases are a major cause of morbidity and mortality in men with prostate cancer. Preclinical studies suggest that osteoclast inhibition might prevent bone metastases. We assessed denosumab, a fully human anti-RANKL monoclonal antibody, for prevention of bone metastasis or death in non-metastatic castration-resistant prostate cancer. Methods In this phase 3, double-blind, randomised, placebo-controlled study, men with non-metastatic castration-resistant prostate cancer at high risk of bone metastasis (prostate-specific antigen [PSA] >= 8.0 mu g/L or PSA doubling time <= 10.0 months, or both) were enrolled at 319 centres from 30 countries. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous denosumab 120 mg or sub cutaneous placebo every 4 weeks. Randomisation was stratified by PSA eligibility criteria and previous or ongoing chemotherapy for prostate cancer. Patients, investigators, and all people involved in study conduct were masked to treatment allocation. The primary endpoint was bone-metastasis-free survival, a composite endpoint determined by time to first occurrence of bone metastasis (symptomatic or asymptomatic) or death from any cause. Efficacy analysis was by intention to treat. The masked treatment phase of the trial has been completed. This trial was registered at ClinicalTrials.gov, number NCT00286091. Findings 1432 patients were randomly assigned to treatment groups (716 denosumab, 716 placebo). Denosumab significantly increased bone-metastasis-free survival by a median of 4.2 months compared with placebo (median 29.5 [95% CI 25.4-33.3] vs 25.2 [22.2-29.5] months; hazard ratio [HR] 0.85, 95% CI 0.73-0.98, p=0.028). Denosumab also significantly delayed time to first bone metastasis (33.2 [95% CI 29.5-38.0] vs 29.5 [22.4-33.1] months; HR 0.84, 95% CI 0.71-0.98, p=0.032). Overall survival did not differ between groups (denosumab, 43.9 [95% CI 40.1-not estimable] months vs placebo, 44.8 [40.1-not estimable] months; HR 1.01, 95% CI 0.85-1.20, p=0.91). Rates of adverse events and serious adverse events were similar in both groups, except for osteonecrosis of the jaw and hypocalcaemia. 33 (5%) patients on denosumab developed osteonecrosis of the jaw versus none on placebo. Hypocalcaemia occurred in 12 (2%) patients on denosumab and two (<1%) on placebo. Interpretation This large randomised study shows that targeting of the bone microenvironment can delay bone metastasis in men with prostate cancer. C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Saad, Fred] Univ Montreal, Ctr Hosp, CRCHUM, Montreal, PQ, Canada. [Coleman, Robert] Weston Pk Hosp, Sheffield, S Yorkshire, England. [Shore, Neal] Carolina Urol Res Ctr, Myrtle Beach, SC USA. [Fizazi, Karim] Univ Paris Sud, Inst Gustave Roussy, Villejuif, France. [Tombal, Bertrand] Clin Univ St Luc, Univ Catholique Louvain, B-1200 Brussels, Belgium. [Miller, Kurt] Charite, Berlin, Germany. [Sieber, Paul] Urol Associates Lancaster, Lancaster, PA USA. [Karsh, Lawrence] Urol Ctr Colorado, Denver, CO USA. [Damiao, Ronaldo] Hosp Univ Pedro Ernesto, Rio De Janeiro, Brazil. [Tammela, Teuvo L.] Tampere Univ Hosp, Tampere, Finland. [Egerdie, Blair] Urol Associates, Urol Med Res, Kitchener, ON, Canada. [Van Poppel, Hendrik] Univ Ziekenhuis Gasthuisberg, Louvain, Belgium. [Chin, Joseph] London Hlth Sci Ctr, London, ON, Canada. [Morote, Juan] Hosp Gen Valle Hebron, Barcelona, Spain. [Gomez-Veiga, Francisco] Complejo Hosp Univ, La Coruna, Spain. [Borkowski, Tomasz] Med Univ Warsaw, Szpital Dzieciatka Jezus, Warsaw, Poland. [Ye, Zhishen; Kupic, Amy; Dansey, Roger; Goessl, Carsten] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu OI TOMBAL, Bertrand/0000-0002-0093-8408 FU Amgen Inc.; Amgen; Novartis FX Amgen Inc.; MRS, RC, KF, and FS have been consultants for Amgen and Novartis. LK, BT, HVP, JC, JM, KM, PS, TLT, and NS have been consultants for Amgen. KF, FS, RC, and BT have participated in speakers' bureaus for Amgen and Novartis. NS, KM, PS, TB, and JM have participated in speakers' bureaus for Amgen. KF has received travel funds from Amgen and Novartis. BE, LK, BT, JC, KM, TB, and NS have received travel funds from Amgen. MRS, FS, LK, TLT, and NS have received research funding from Amgen. RC has received research funding from Novartis and honoraria from Amgen and Novartis. MRS, LK, and NS have received honoraria from Amgen. RC has provided expert testimony for Novartis. FG-V and RD declare that they have no conflicts of interest. ZY, AK, RD, and CG are employees of Amgen and have received stock or stock options from Amgen. NR 30 TC 301 Z9 310 U1 4 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JAN 7 PY 2012 VL 379 IS 9810 BP 39 EP 46 DI 10.1016/S0140-6736(11)61226-9 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 873WC UT WOS:000298913000036 PM 22093187 ER PT J AU Lieber, DS Vafai, SB Horton, LC Slate, NG Liu, ST Borowsky, ML Calvo, SE Schmahmann, JD Mootha, VK AF Lieber, Daniel S. Vafai, Scott B. Horton, Laura C. Slate, Nancy G. Liu, Shangtao Borowsky, Mark L. Calvo, Sarah E. Schmahmann, Jeremy D. Mootha, Vamsi K. TI Atypical case of Wolfram syndrome revealed through targeted exome sequencing in a patient with suspected mitochondrial disease SO BMC MEDICAL GENETICS LA English DT Article ID RESPONSIVE MEGALOBLASTIC-ANEMIA; GENOTYPE-PHENOTYPE CORRELATION; DOMINANT OPTIC ATROPHY; DIABETES-MELLITUS; WFS1 GENE; TRANSMEMBRANE PROTEIN; HEARING IMPAIRMENT; MISSENSE MUTATION; IDENTIFICATION; FAMILIES AB Background: Mitochondrial diseases comprise a diverse set of clinical disorders that affect multiple organ systems with varying severity and age of onset. Due to their clinical and genetic heterogeneity, these diseases are difficult to diagnose. We have developed a targeted exome sequencing approach to improve our ability to properly diagnose mitochondrial diseases and apply it here to an individual patient. Our method targets mitochondrial DNA (mtDNA) and the exons of 1,600 nuclear genes involved in mitochondrial biology or Mendelian disorders with multi-system phenotypes, thereby allowing for simultaneous evaluation of multiple disease loci. Case Presentation: Targeted exome sequencing was performed on a patient initially suspected to have a mitochondrial disorder. The patient presented with diabetes mellitus, diffuse brain atrophy, autonomic neuropathy, optic nerve atrophy, and a severe amnestic syndrome. Further work-up revealed multiple heteroplasmic mtDNA deletions as well as profound thiamine deficiency without a clear nutritional cause. Targeted exome sequencing revealed a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome. Conclusion: This case demonstrates how clinical application of next-generation sequencing technology can enhance the diagnosis of patients suspected to have rare genetic disorders. Furthermore, the finding of unexplained thiamine deficiency in a patient with Wolfram syndrome suggests a potential link between WFS1 biology and thiamine metabolism that has implications for the clinical management of Wolfram syndrome patients. C1 [Schmahmann, Jeremy D.] Harvard Univ, Massachusetts Gen Hosp, Ataxia Unit,Cognit & Behav Neurol Unit,Sch Med, Lab Neuroanat & Cerebellar Neurobiol,Dept Neurol, Boston, MA 02114 USA. [Lieber, Daniel S.; Vafai, Scott B.; Slate, Nancy G.; Liu, Shangtao; Borowsky, Mark L.; Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lieber, Daniel S.; Vafai, Scott B.; Slate, Nancy G.; Liu, Shangtao; Calvo, Sarah E.; Mootha, Vamsi K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lieber, Daniel S.; Vafai, Scott B.; Calvo, Sarah E.; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Lieber, Daniel S.; Vafai, Scott B.; Borowsky, Mark L.; Calvo, Sarah E.; Mootha, Vamsi K.] Broad Inst Harvard & MIT, Cambridge, MA 02141 USA. [Vafai, Scott B.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Vafai, Scott B.] Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. RP Schmahmann, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ataxia Unit,Cognit & Behav Neurol Unit,Sch Med, Lab Neuroanat & Cerebellar Neurobiol,Dept Neurol, Boston, MA 02114 USA. EM jschmahmann@partners.org; vamsi@hms.harvard.edu OI Horton, Laura/0000-0002-7098-3650 FU NIH/NHGRI [RC2HG005556]; NIH/NIDDK [T32 DK007028 37]; NSF; MINDlink Foundation; Birmingham Foundation FX This research was supported by NIH/NHGRI grant RC2HG005556 (VKM), NIH/NIDDK grant T32 DK007028 37 (SBV), an NSF Graduate Research Fellowship Program grant (DSL), and the MINDlink and Birmingham Foundations (JDS). The authors would like to thank Molly Plovanich and Dr. Joseph Avruch for comments on the manuscript. NR 29 TC 19 Z9 20 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD JAN 6 PY 2012 VL 13 AR 3 DI 10.1186/1471-2350-13-3 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 894NL UT WOS:000300433400001 PM 22226368 ER PT J AU Navarrett, S Collier, L Cardozo, C Dracheva, S AF Navarrett, Scott Collier, Lauren Cardozo, Christopher Dracheva, Stella TI Alterations of serotonin 2C and 2A receptors in response to T10 spinal cord transection in rats SO NEUROSCIENCE LETTERS LA English DT Article DE Rat; SCI; 5-HT2(A)R; 5-HT2(c)R; mRNA editing ID PRE-MESSENGER-RNA; G-PROTEIN; CONSTITUTIVE ACTIVITY; PREFRONTAL CORTEX; SUICIDE; NEURONS; INJURY; BRAIN AB Recent studies reported that a recovery of motoneurons after spinal cord transection at the sacrocaudal level may depend on adaptive alterations of the serotonin 2C (5-HT2cR) and 2A (5-HT2cR) receptor function via changes in mRNA editing or protein expression, respectively. It has been suggested that depletion of serotonergic input may drive these adaptations. Here, mRNA editing and/or expression of 5-HT2cR and 5-HT2AR was evaluated in rats that sustained a complete transection at the thoracic (T10) level. While 5-HT2AR mRNA expression was upregulated below the site of spinal cord injury (SCI), no changes in 5-HT2cR mRNA editing or expression were detected. These findings argue against the hypothesis that 5-HT2cR editing is regulated by extracellular serotonin levels. Rather, it appears that the editing process is just one of the ways in which excitability of motor neurons can be restored following SCI. To this end, the influence of excitatory locomotor circuits on motor neurons in the thoracic spinal cord of rats requires further exploration. Published by Elsevier Ireland Ltd. C1 [Cardozo, Christopher; Dracheva, Stella] James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences SCI, Bronx, NY 10468 USA. [Cardozo, Christopher] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Cardozo, Christopher] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Dracheva, Stella] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Dracheva, S (reprint author), James J Peters Vet Affairs Med Ctr, Ctr Excellence Med Consequences SCI, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Stella.Dracheva@mssm.edu FU Department of Veterans Affairs Office of Research and Development; VISN3 Mental Illness Research and Education Clinical Center; VA FX This work was supported by Department of Veterans Affairs Office of Research and Development and VISN3 Mental Illness Research and Education Clinical Center (SD) and by a VA Merit Award (SD). NR 31 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 6 PY 2012 VL 506 IS 1 BP 74 EP 78 DI 10.1016/j.neulet.2011.10.052 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 891GK UT WOS:000300205000015 PM 22056918 ER PT J AU Camahort, R Cowan, CA AF Camahort, Raymond Cowan, Chad A. TI Cbx Proteins Help ESCs Walk the Line between Self-Renewal and Differentiation SO CELL STEM CELL LA English DT Editorial Material ID X-INACTIVATION; POLYCOMB; GENES AB The Polycomb repressive complexes (PRC) regulate self-renewal and differentiation in embryonic stem cells (ESCs). In this issue of Cell Stem Cell, Morey et al. (2012) and O'Loghlen et al. (2012) report that dynamic interchange of PRC subunits modulates the balance between self-renewal and lineage commitment in ESCs. C1 [Camahort, Raymond; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Camahort, Raymond; Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. RP Cowan, CA (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM ccowan@fas.harvard.edu NR 11 TC 4 Z9 4 U1 0 U2 4 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 JAN 6 PY 2012 VL 10 IS 1 BP 4 EP 6 DI 10.1016/j.stem.2011.12.011 PG 3 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 880ZQ UT WOS:000299449500003 PM 22226347 ER PT J AU Ruckh, JM Zhao, JW Shadrach, JL van Wijngaarden, P Rao, TN Wagers, AJ Franklin, RJM AF Ruckh, Julia M. Zhao, Jing-Wei Shadrach, Jennifer L. van Wijngaarden, Peter Rao, Tata Nageswara Wagers, Amy J. Franklin, Robin J. M. TI Rejuvenation of Regeneration in the Aging Central Nervous System SO CELL STEM CELL LA English DT Article ID OLIGODENDROCYTE PRECURSOR CELLS; REMYELINATION EFFICIENCY; CHEMOKINE RECEPTOR; MULTIPLE-SCLEROSIS; HEMATOPOIETIC STEM; CNS REMYELINATION; PROGENITOR CELLS; DIFFERENTIATION; REPAIR; MICE AB Remyelination is a regenerative process in the central nervous system (CNS) that produces new myelin sheaths from adult stem cells. The decline in remyelination that occurs with advancing age poses a significant barrier to therapy in the CNS, particularly for long-term demyelinating diseases such as multiple sclerosis (MS). Here we show that remyelination of experimentally induced demyelination is enhanced in old mice exposed to a youthful systemic milieu through heterochronic parabiosis. Restored remyelination in old animals involves recruitment to the repairing lesions of blood-derived monocytes from the young parabiotic partner, and preventing this recruitment partially inhibits rejuvenation of remyelination. These data suggest that enhanced remyelinating activity requires both youthful monocytes and other factors, and that remyelination-enhancing therapies targeting endogenous cells can be effective throughout life. C1 [Shadrach, Jennifer L.; Rao, Tata Nageswara; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Howard Hughes Med Inst, Cambridge, MA 02215 USA. [Ruckh, Julia M.; Zhao, Jing-Wei; van Wijngaarden, Peter; Franklin, Robin J. M.] Univ Cambridge, MRC Ctr Stem Cell Biol & Regenerat Med, Cambridge CB3 0ES, England. [Ruckh, Julia M.; Zhao, Jing-Wei; van Wijngaarden, Peter; Franklin, Robin J. M.] Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge CB3 0ES, England. [Ruckh, Julia M.; Zhao, Jing-Wei; van Wijngaarden, Peter; Franklin, Robin J. M.] Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England. [Shadrach, Jennifer L.; Rao, Tata Nageswara; Wagers, Amy J.] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02215 USA. [Shadrach, Jennifer L.; Rao, Tata Nageswara; Wagers, Amy J.] Joslin Diabet Ctr, Cambridge, MA 02215 USA. RP Wagers, AJ (reprint author), Harvard Univ, Harvard Stem Cell Inst, Howard Hughes Med Inst, 7 Divin Ave, Cambridge, MA 02215 USA. EM amy.wagers@joslin.harvard.edu; rjf1000@cam.ac.uk RI Zhao, Jing-Wei/A-6887-2012; Zhao, Jing-Wei/L-9964-2014 OI Zhao, Jing-Wei/0000-0002-1135-9743 FU European Leukodystrophy Association (ELA); Research into Ageing; UK Multiple Sclerosis Society; National Multiple Sclerosis Society; Burroughs-Wellcome Fund; Harvard Stem Cell Institute; British Consulate General Science and Innovation Network; National Institutes of Health [1 DP2 OD004345-01]; National Health and Medical Research Council of Australia; Medical Research Council, UK FX We thank G. Buruzula and J. LaVecchio at Joslin's HSCl/DERC Flow Cytometry Core (NIH P30 DK036836) for their excellent technical support. This work was supported in part by grants from the European Leukodystrophy Association (ELA) (to R.J.M.F. and A.J.W), Research into Ageing, the UK Multiple Sclerosis Society and National Multiple Sclerosis Society (to R.J.M.F.), the Burroughs-Wellcome Fund, the Harvard Stem Cell Institute, the British Consulate General Science and Innovation Network, and National Institutes of Health 1 DP2 OD004345-01 (to A.J.W.). P.v.W. was supported by the National Health and Medical Research Council of Australia. J.M.R. was supported by a Ph.D. studentship from the Medical Research Council, UK. NR 30 TC 173 Z9 178 U1 3 U2 40 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 JAN 6 PY 2012 VL 10 IS 1 BP 96 EP 103 DI 10.1016/j.stem.2011.11.019 PG 8 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 880ZQ UT WOS:000299449500014 PM 22226359 ER PT J AU Cash, JN Angerman, EB Kattamuri, C Nolan, K Zhao, HY Sidis, Y Keutmann, HT Thompson, TB AF Cash, Jennifer N. Angerman, Elizabeth B. Kattamuri, Chandramohan Nolan, Kristof Zhao, Huaying Sidis, Yisrael Keutmann, Henry T. Thompson, Thomas B. TI Structure of Myostatin.Follistatin-like 3 N-TERMINAL DOMAINS OF FOLLISTATIN-TYPE MOLECULES EXHIBIT ALTERNATE MODES OF BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MASS-TRANSPORT LIMITATION; SKELETAL-MUSCLE MASS; TGF-BETA; ACTIVIN-BINDING; SURFACE BINDING; MACROMOLECULAR STRUCTURES; BIOLOGICAL-ACTIVITY; THERAPEUTIC TARGET; CRYSTAL-STRUCTURE; GDF-8 PROPEPTIDE AB TGF-beta family ligands are involved in a variety of critical physiological processes. For instance, the TGF-beta ligand myostatin is a staunch negative regulator of muscle growth and a therapeutic target for muscle-wasting disorders. Therefore, it is important to understand the molecular mechanisms of TGF-beta family regulation. One form of regulation is through inhibition by extracellular antagonists such as the follistatin (Fst)-type proteins. Myostatin is tightly controlled by Fst-like 3 (Fstl3), which is the only Fst-type molecule that has been identified in the serum bound to myostatin. Here, we present the crystal structure of myostatin in complex with Fstl3. The structure reveals that the N-terminal domain (ND) of Fstl3 interacts uniquely with myostatin as compared with activin A, because it utilizes different surfaces on the ligand. This results in conformational differences in the ND of Fstl3 that alter its position in the type I receptor-binding site of the ligand. We also show that single point mutations in the ND of Fstl3 are detrimental to ligand binding, whereas corresponding mutations in Fst have little effect. Overall, we have shown that the NDs of Fst-type molecules exhibit distinctive modes of ligand binding, which may affect overall affinity of ligand.Fst-type protein complexes. C1 [Cash, Jennifer N.; Angerman, Elizabeth B.; Kattamuri, Chandramohan; Nolan, Kristof; Thompson, Thomas B.] Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Zhao, Huaying] NIBIB, Lab Cellular Imaging & Mol Biophys, NIH, Bethesda, MD 20892 USA. [Sidis, Yisrael] CHU Vaudois, Dept Endocrinol Diabet & Metab, CH-1011 Lausanne, Switzerland. [Keutmann, Henry T.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Thompson, TB (reprint author), Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Med Sci Bldg,231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM thompstb@ucmail.uc.edu RI Zhao, Huaying/F-5716-2012 FU National Institutes of Health [GM084186]; Muscular Dystrophy Association [93887]; NIBIB, National Institutes of Health; American Heart Association FX This work was supported, in whole or in part, by National Institutes of Health Grant GM084186 (to T. B. T.). This work was also supported by Muscular Dystrophy Association Grant 93887 (to T. B. T.) and the Intramural Research Program of the NIBIB, National Institutes of Health.; Supported by an American Heart Association predoctoral fellowship. NR 56 TC 28 Z9 30 U1 0 U2 5 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 JAN 6 PY 2012 VL 287 IS 2 BP 1043 EP 1053 DI 10.1074/jbc.M111.270801 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 877IE UT WOS:000299170300021 PM 22052913 ER PT J AU Mochel, F Durant, B Meng, XL O'Callaghan, J Yu, H Brouillet, E Wheeler, VC Humbert, S Schiffmann, R Durr, A AF Mochel, Fanny Durant, Brandon Meng, Xingli O'Callaghan, James Yu, Hua Brouillet, Emmanuel Wheeler, Vanessa C. Humbert, Sandrine Schiffmann, Raphael Durr, Alexandra TI Early Alterations of Brain Cellular Energy Homeostasis in Huntington Disease Models SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCUSED MICROWAVE IRRADIATION; CAG REPEAT INSTABILITY; KNOCK-IN MICE; CREATINE-KINASE; TRANSGENIC MICE; TRINUCLEOTIDE REPEAT; MUTANT HUNTINGTIN; CLINICAL SYMPTOMS; MOUSE-BRAIN; MITOCHONDRIAL AB Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in Hdh(Q111/+) mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool. C1 [Mochel, Fanny] Hop La Pitie Salpetriere, Brain & Spine Inst, INSERM UMR S975, F-75013 Paris, France. [Mochel, Fanny; Durr, Alexandra] Hop La Pitie Salpetriere, AP HP, Dept Genet, F-75013 Paris, France. [Mochel, Fanny] Univ Paris 06, F-75005 Paris, France. [Mochel, Fanny; Durant, Brandon; Meng, Xingli] Baylor Res Inst, Inst Metab Dis, Dallas, TX 75226 USA. [O'Callaghan, James] NIOSH, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA. [Yu, Hua; Humbert, Sandrine; Schiffmann, Raphael] INSERM U1005, Inst Curie, CNRS UMR3306, F-91405 Orsay, France. [Brouillet, Emmanuel] CEA, URA CEA CNRS 2210, Serv MIRCen, F-92265 Fontenay Aux Roses, France. [Wheeler, Vanessa C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Mochel, F (reprint author), Hop La Pitie Salpetriere, Brain & Spine Inst, INSERM UMR S975, F-75013 Paris, France. EM fanny.mochel@upmc.fr RI Brouillet, Emmanuel/B-4784-2014; Humbert, Sandrine/S-2981-2016; OI Brouillet, Emmanuel/0000-0001-6322-7403; Durant, Brandon/0000-0003-3028-6161 FU National Institutes of Health [NS32765, NS049206]; CHDI Foundation, Inc. FX This work was supported, in whole or in part, by National Institutes of Health Grants NS32765 and NS049206 (to V. C. W.). This work was also supported by the CHDI Foundation, Inc. NR 47 TC 51 Z9 52 U1 0 U2 2 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 JAN 6 PY 2012 VL 287 IS 2 BP 1361 EP 1370 DI 10.1074/jbc.M111.309849 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 877IE UT WOS:000299170300050 PM 22123819 ER PT J AU Braunwald, E AF Braunwald, Eugene TI On Circadian Variation of Myocardial Reperfusion Injury SO CIRCULATION RESEARCH LA English DT Editorial Material ID GENE-EXPRESSION; INFARCTION; CLOCK; ONSET; HEART; RHYTHMS; DISEASE C1 [Braunwald, Eugene] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 23 TC 3 Z9 3 U1 0 U2 0 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 JAN 6 PY 2012 VL 110 IS 1 BP 6 EP 7 DI 10.1161/CIRCRESAHA.111.260265 PG 2 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 875IO UT WOS:000299023800002 PM 22223205 ER PT J AU Aldridge, BB Fernandez-Suarez, M Heller, D Ambravaneswaran, V Irimia, D Toner, M Fortune, SM AF Aldridge, Bree B. Fernandez-Suarez, Marta Heller, Danielle Ambravaneswaran, Vijay Irimia, Daniel Toner, Mehmet Fortune, Sarah M. TI Asymmetry and Aging of Mycobacterial Cells Lead to Variable Growth and Antibiotic Susceptibility SO SCIENCE LA English DT Article ID BACILLUS-SUBTILIS; SIZE CONTROL; DIVISION; PROTEINS; LOCALIZATION; TUBERCULOSIS; CYCLE; SPORULATION; PERSISTENCE; SWITCH AB Cells use both deterministic and stochastic mechanisms to generate cell-to-cell heterogeneity, which enables the population to better withstand environmental stress. Here we show that, within a clonal population of mycobacteria, there is deterministic heterogeneity in elongation rate that arises because mycobacteria grow in an unusual, unipolar fashion. Division of the asymmetrically growing mother cell gives rise to daughter cells that differ in elongation rate and size. Because the mycobacterial cell division cycle is governed by time, not cell size, rapidly elongating cells do not divide more frequently than slowly elongating cells. The physiologically distinct subpopulations of cells that arise through asymmetric growth and division are differentially susceptible to clinically important classes of antibiotics. C1 [Aldridge, Bree B.; Fernandez-Suarez, Marta; Heller, Danielle; Fortune, Sarah M.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Fernandez-Suarez, Marta; Ambravaneswaran, Vijay; Irimia, Daniel; Toner, Mehmet] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Fortune, Sarah M.] MIT, Ragon Inst MGH, Boston, MA 02129 USA. RP Fortune, SM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM sfortune@hsph.harvard.edu OI Aldridge, Bree/0000-0003-2236-1424; Irimia, Daniel/0000-0001-7347-2082 FU National Institute of Health [1DP20D001378]; Doris Duke Charitable Foundation [2010054]; United States Army Medical Research Acquisition Activity [W81XWH-10-2-0161]; National Institute of Biomedical Imaging and Bioengineering [P41 EB002503]; Massachusetts General Hospital Executive Committee on Research FX We thank E. Rubin, B. Bloom, C. Sassetti, D. Lauffenburger, E. Liu, and J. Model for helpful discussions; P. Sorger for access to his live-cell imaging systems; A. J. Aranyosi for assistance with microfabrication; J. Goldstein for help with image annotation; and J. Sinn-Hanlon for the device illustration. We thank R. Husson and M. Mir for the gift of Van-Alexa. B. B. A. and S. M. F. designed the experiments and wrote the initial manuscript. B. B. A. performed the experiments, annotated images, and developed the analysis programs. M.F.-S., V. A., D. I., and M. T. designed the microfluidic devices that were built by M.F.-S. D. H. performed the initial pulse-chase experiment and annotated images. This work was partially supported by a National Institute of Health Director's New Innovator Award 1DP20D001378, Doris Duke Charitable Foundation under grant 2010054, and United States Army Medical Research Acquisition Activity under grant W81XWH-10-2-0161 to S. M. F., the National Institute of Biomedical Imaging and Bioengineering under grant P41 EB002503 to M. T. (BioMEMS Resource Center), and by the Massachusetts General Hospital Executive Committee on Research through a postdoctoral fellowship to M.F.S. NR 29 TC 114 Z9 117 U1 6 U2 58 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 6 PY 2012 VL 335 IS 6064 BP 100 EP 104 DI 10.1126/science.1216166 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 872YA UT WOS:000298846200060 PM 22174129 ER PT J AU Paul, E Catlin, EA Cummings, BM AF Paul, Elahna Catlin, Elizabeth A. Cummings, Brian M. TI Case 26-2011: A Boy with a Complex Kidney Cyst REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Paul, Elahna; Catlin, Elizabeth A.; Cummings, Brian M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Paul, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. 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 JAN 5 PY 2012 VL 366 IS 1 BP 94 EP 95 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 887XY UT WOS:000299968800027 ER PT J AU Jagasia, M Arora, M Flowers, MED Chao, NJ McCarthy, PL Cutler, CS Urbano-Ispizua, A Pavletic, SZ Haagenson, MD Zhang, MJ Antin, JH Bolwell, BJ Bredeson, C Cahn, JY Cairo, M Gale, RP Gupta, V Lee, SJ Litzow, M Weisdorf, DJ Horowitz, MM Hahn, T AF Jagasia, Madan Arora, Mukta Flowers, Mary E. D. Chao, Nelson J. McCarthy, Philip L. Cutler, Corey S. Urbano-Ispizua, Alvaro Pavletic, Steven Z. Haagenson, Michael D. Zhang, Mei-Jie Antin, Joseph H. Bolwell, Brian J. Bredeson, Christopher Cahn, Jean-Yves Cairo, Mitchell Gale, Robert Peter Gupta, Vikas Lee, Stephanie J. Litzow, Mark Weisdorf, Daniel J. Horowitz, Mary M. Hahn, Theresa TI Risk factors for acute GVHD and survival after hematopoietic cell transplantation SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; UNRELATED DONORS; ALLOGENEIC TRANSPLANTATION; CYCLOSPORINE CONCENTRATION; COMPARING METHOTREXATE; IDENTICAL SIBLINGS; SOCIETE-FRANCAISE; RANDOMIZED-TRIAL; APLASTIC-ANEMIA AB Risk factors for acute GVHD (AGVHD), overall survival, and transplant-related mortality were evaluated in adults receiving allogeneic hematopoietic cell transplants (19992005) from HLA-identical sibling donors (SDs; n = 3191) or unrelated donors (URDs; n = 2370) and reported to the Center for International Blood and Marrow Transplant Research, Minneapolis, MN. To understand the impact of transplant regimen on AGVHD risk, 6 treatment categories were evaluated: (1) myeloablative conditioning (MA) with total body irradiation (TBI) + PBSCs, (2) MA + TBI + BM, (3) MA + nonTBI + PBSCs, (4) MA + nonTBI + BM, (5) reduced intensity conditioning (RIC) + PBSCs, and (6) RIC + BM. The cumulative incidences of grades B-D AGVHD were 39% (95% confidence interval [CI], 37%-41%) in the SD cohort and 59% (95% CI, 57%-61%) in the URD cohort. Patients receiving SD transplants with MA + nonTBI + BM and RIC + PBSCs had significantly lower risks of grades B-D AGVHD than patients in other treatment categories. Those receiving URD transplants with MA + TBI + BM, MA + nonTBI + BM, RIC + BM, orRIC + PBSCs had lower risks of grades B-D AGVHD than those in other treatment categories. The 5-year probabilities of survival were 46% (95% CI, 44%-49%) with SD transplants and 33% (95% CI, 31%-35%) with URD transplants. Conditioning intensity, TBI and graft source have a combined effect on risk of AGVHD that must be considered in deciding on a treatment strategy for individual patients. (Blood. 2012; 119(1): 296-307) C1 [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect, Vanderbilt Clin 3973, Nashville, TN 37232 USA. [Arora, Mukta; Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA. [Flowers, Mary E. D.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Flowers, Mary E. D.; Lee, Stephanie J.] Univ Washington, Seattle, WA 98195 USA. [Chao, Nelson J.] Duke Univ, Med Ctr, Durham, NC USA. [McCarthy, Philip L.; Hahn, Theresa] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Cutler, Corey S.; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Urbano-Ispizua, Alvaro] Hosp Clin Barcelona, Barcelona, Spain. [Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Haagenson, Michael D.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Zhang, Mei-Jie; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Bolwell, Brian J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Bredeson, Christopher] Univ Ottawa, Ottawa Hosp, Blood & Marrow Transplant Program, Ottawa, ON, Canada. [Cahn, Jean-Yves] Ctr Hosp Grenoble, Hosp A Michallon, Grenoble, France. [Cairo, Mitchell] Columbia Univ, New York Med Coll, Med Ctr, New York, NY USA. [Gale, Robert Peter] Ctr Adv Studies Leukemia, Los Angeles, CA USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Litzow, Mark] Mayo Clin, Rochester, MN USA. RP Jagasia, M (reprint author), Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect, Vanderbilt Clin 3973, Nashville, TN 37232 USA. EM madan.jagasia@vanderbilt.edu RI Cahn, Jean-Yves/M-6493-2014 FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung, and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research [N00014-061-0704, N00014-08-1-0058]; Allos Inc; Amgen Inc; Angioblast; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America Inc; Gamida Cell Teva Joint Venture Ltd; Genentech Inc; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; Leukemia & Lymphoma Society; Medical College of Wisconsin; Millennium Pharmaceuticals Inc; Milliman USA Inc; Miltenyi Biotec Inc; National Marrow Donor Program; Optum Healthcare Solutions Inc; Otsuka America Pharmaceutical Inc; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix Inc; Swedish Orphan Biovitrum; THERAKOS Inc; Wellpoint Inc FX The CIBMTR is supported by Public Health Service grant/cooperative agreement U24-CA76518 from the National Cancer Institute (NCI); the National Heart, Lung, and Blood Institute (NHLBI); and the National Institute of Allergy and Infectious Diseases (NIAID); grant/cooperative agreement 5U01HL069294 from NHLBI and NCI; contract HHSH234200637015C with Health Resources and Services Administration; grants N00014-061-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from Allos Inc; Amgen Inc; Angioblast; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Buchanan Family Foundation; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Children's Leukemia Research Association; Fresenius-Biotech North America Inc; Gamida Cell Teva Joint Venture Ltd; Genentech Inc; Genzyme Corporation; GlaxoSmithKline; Kiadis Pharma; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Millennium Pharmaceuticals Inc; Milliman USA Inc; Miltenyi Biotec Inc; National Marrow Donor Program; Optum Healthcare Solutions Inc; Otsuka America Pharmaceutical Inc; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix Inc; Swedish Orphan Biovitrum; THERAKOS Inc; and Wellpoint Inc. NR 44 TC 132 Z9 137 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 5 PY 2012 VL 119 IS 1 BP 296 EP 307 DI 10.1182/blood-2011-06-364265 PG 12 WC Hematology SC Hematology GA 875EE UT WOS:000299012400036 PM 22010102 ER PT J AU Duan, S Cermak, L Pagan, JK Rossi, M Martinengo, C di Celle, PF Chapuy, B Shipp, M Chiarle, R Pagano, M AF Duan, Shanshan Cermak, Lukas Pagan, Julia K. Rossi, Mario Martinengo, Cinzia di Celle, Paola Francia Chapuy, Bjoern Shipp, Margaret Chiarle, Roberto Pagano, Michele TI FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas SO NATURE LA English DT Article ID SCF UBIQUITIN LIGASE; GENE-EXPRESSION; PATHOGENESIS AB BCL6 is the product of a proto-oncogene implicated in the pathogenesis of human B-cell lymphomas(1,2). By binding specific DNA sequences, BCL6 controls the transcription of a variety of genes involved in B-cell development, differentiation and activation. BCL6 is overexpressed in the majority of patients with aggressive diffuse large B-cell lymphoma (DLBCL), the most common lymphoma in adulthood, and transgenic mice constitutively expressing BCL6 in B cells develop DLBCLs similar to the human disease(3,4). In many DLBCL patients, BCL6 overexpression is achieved through translocation (similar to 40%) or hypermutation of its promoter (similar to 15%). However, many other DLBCLs overexpress BCL6 through an unknown mechanism. Here we show that BCL6 is targeted for ubiquitylation and proteasomal degradation by a SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complex that contains the orphan F-box protein FBXO11 (refs 5, 6). The gene encoding FBXO11 was found to be deleted or mutated in multiple DLBCL cell lines, and this inactivation of FBXO11 correlated with increased levels and stability of BCL6. Similarly, FBXO11 was either deleted or mutated in primary DLBCLs. Notably, tumour-derived FBXO11 mutants displayed an impaired ability to induce BCL6 degradation. Reconstitution of FBXO11 expression in FBXO11-deleted DLBCL cells promoted BCL6 ubiquitylation and degradation, inhibited cell proliferation, and induced cell death. FBXO11-deleted DLBCL cells generated tumours in immunodeficient mice, and the tumorigenicity was suppressed by FBXO11 reconstitution. We reveal a molecular mechanism controlling BCL6 stability and propose that mutations and deletions in FBXO11 contribute to lymphomagenesis through BCL6 stabilization. The deletions/mutations found in DLBCLs are largely monoallelic, indicating that FBXO11 is a haplo-insufficient tumour suppressor gene. C1 [Duan, Shanshan; Cermak, Lukas; Pagan, Julia K.; Rossi, Mario; Pagano, Michele] NYU, Sch Med, NYU Canc Inst, Dept Pathol, New York, NY 10016 USA. [Duan, Shanshan; Cermak, Lukas; Pagan, Julia K.; Pagano, Michele] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. [Martinengo, Cinzia; Chiarle, Roberto] Univ Turin, CERMS, Dept Biomed Sci & Human Oncol, I-10126 Turin, Italy. [di Celle, Paola Francia] San Giovanni Battista Hosp, I-10126 Turin, Italy. [Chapuy, Bjoern; Shipp, Margaret] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pagano, M (reprint author), NYU, Sch Med, NYU Canc Inst, Dept Pathol, 522 1st Ave,SRB 1107, New York, NY 10016 USA. EM roberto.chiarle@unito.it; michele.pagano@nyumc.org RI Rossi, Mario/E-7666-2012; Cermak, Lukas/N-2254-2016; OI Rossi, Mario/0000-0001-6349-8895; Cermak, Lukas/0000-0002-8777-3692; CHIARLE, Roberto/0000-0003-1564-8531; pagano, michele/0000-0003-3210-2442 FU National Institutes of Health [R01-GM57587, R37-CA76584, R21-CA161108, PO1-CA092625]; Susan G. Komen for the Cure; Lymphoma Research Foundation; AIRC; ERC [ERC-2009-StG-Proposal No242965-LUNELY] FX We thank W. Carroll, S. Shaham and L. Staudt for sharing unpublished results; A. Melnick, Y. Sun and Y. Xiong for reagents; L. Cerchietti, Y. Cheng, E. Dehan, V. Donato, N. V. Dorello, S. N. Yang and Z. Yao for advice and/or contributions to this work. M. P. is grateful to T. M. Thor and K. E. Davidson, and L. C. to Zuzana S. for continuous support. This work was supported by grants from the National Institutes of Health to M. P. (R01-GM57587, R37-CA76584 and R21-CA161108) and M. S. (PO1-CA092625), a grant from Susan G. Komen for the Cure to S. D., a Lymphoma Research Foundation Fellowship to J.K.P. and grants from AIRC and ERC (ERC-2009-StG-Proposal No242965-LUNELY) to R. C. M. P. is an Investigator with the Howard Hughes Medical Institute. NR 19 TC 90 Z9 97 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 5 PY 2012 VL 481 IS 7379 BP 90 EP U100 DI 10.1038/nature10688 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 872VD UT WOS:000298836900035 PM 22113614 ER PT J AU Djebali, S Lagarde, J Kapranov, P Lacroix, V Borel, C Mudge, JM Howald, C Foissac, S Ucla, C Chrast, J Ribeca, P Martin, D Murray, RR Yang, XP Ghamsari, L Lin, CW Bell, I Dumais, E Drenkow, J Tress, ML Gelpi, JL Orozco, M Valencia, A van Berkum, NL Lajoie, BR Vidal, M Stamatoyannopoulos, J Batut, P Dobin, A Harrow, J Hubbard, T Dekker, J Frankish, A Salehi-Ashtiani, K Reymond, A Antonarakis, SE Guigo, R Gingeras, TR AF Djebali, Sarah Lagarde, Julien Kapranov, Philipp Lacroix, Vincent Borel, Christelle Mudge, Jonathan M. Howald, Cedric Foissac, Sylvain Ucla, Catherine Chrast, Jacqueline Ribeca, Paolo Martin, David Murray, Ryan R. Yang, Xinping Ghamsari, Lila Lin, Chenwei Bell, Ian Dumais, Erica Drenkow, Jorg Tress, Michael L. Lluis Gelpi, Josep Orozco, Modesto Valencia, Alfonso van Berkum, Nynke L. Lajoie, Bryan R. Vidal, Marc Stamatoyannopoulos, John Batut, Philippe Dobin, Alex Harrow, Jennifer Hubbard, Tim Dekker, Job Frankish, Adam Salehi-Ashtiani, Kourosh Reymond, Alexandre Antonarakis, Stylianos E. Guigo, Roderic Gingeras, Thomas R. TI Evidence for Transcript Networks Composed of Chimeric RNAs in Human Cells SO PLOS ONE LA English DT Article ID HUMAN GENOME; REVERSE TRANSCRIPTION; GENE FUSION; ANNOTATION; DISCOVERY; ENCODE; SITES; TOOL; ELEMENTS; CLONING AB The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5' and 3' transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network. C1 [Djebali, Sarah; Lagarde, Julien; Lacroix, Vincent; Foissac, Sylvain; Ribeca, Paolo; Martin, David; Guigo, Roderic] Ctr Genom Regulat, Barcelona, Catalonia, Spain. [Guigo, Roderic] Univ Pompeu Fabra, Dept Ciences Expt & Salut, Barcelona, Catalonia, Spain. [Kapranov, Philipp; Foissac, Sylvain; Bell, Ian; Dumais, Erica; Gingeras, Thomas R.] Affymetrix Inc, Santa Clara, CA USA. [Borel, Christelle; Ucla, Catherine; Antonarakis, Stylianos E.] Univ Geneva, Sch Med, Dept Genet Med & Dev, Univ Hosp Geneva, CH-1211 Geneva, Switzerland. [Mudge, Jonathan M.; Harrow, Jennifer; Hubbard, Tim; Frankish, Adam] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Howald, Cedric; Chrast, Jacqueline; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland. [Murray, Ryan R.; Yang, Xinping; Ghamsari, Lila; Lin, Chenwei; Vidal, Marc; Salehi-Ashtiani, Kourosh] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Murray, Ryan R.; Yang, Xinping; Ghamsari, Lila; Lin, Chenwei; Vidal, Marc; Salehi-Ashtiani, Kourosh] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Murray, Ryan R.; Yang, Xinping; Ghamsari, Lila; Lin, Chenwei; Vidal, Marc; Salehi-Ashtiani, Kourosh] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Drenkow, Jorg; Batut, Philippe; Dobin, Alex; Gingeras, Thomas R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Tress, Michael L.; Valencia, Alfonso] Spanish Natl Canc Res Ctr, Struct Biol & Biocomp Programme, Madrid, Spain. [Lluis Gelpi, Josep; Orozco, Modesto] Univ Barcelona, Fac Biol, Inst Res Biomed, Barcelona, Catalonia, Spain. [Lluis Gelpi, Josep; Orozco, Modesto] Univ Barcelona, Fac Biol, Barcelona Supercomp Ctr, Joint Program Computat Biol, Barcelona, Catalonia, Spain. [Stamatoyannopoulos, John] Univ Washington, Seattle, WA 98195 USA. [van Berkum, Nynke L.; Lajoie, Bryan R.; Dekker, Job] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA USA. [Salehi-Ashtiani, Kourosh] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA. [Salehi-Ashtiani, Kourosh] New York Univ Abu Dhabi, Abu Dhabi, U Arab Emirates. RP Djebali, S (reprint author), Ctr Genom Regulat, Barcelona, Catalonia, Spain. EM Stylianos.Antonarakis@unige.ch; roderic.guigo@crg.cat; gingeras@cshl.edu RI Antonarakis, Stylianos/N-8866-2014; Djebali, Sarah/O-9817-2014; Gelpi, Josep Lluis/M-6401-2013; Guigo, Roderic/D-1303-2010; Hubbard, Tim/C-2567-2008; Valencia, Alfonso/I-3127-2015; Lacroix, Vincent/M-2906-2015; OI Antonarakis, Stylianos/0000-0001-8907-5823; Djebali, Sarah/0000-0002-0599-1267; Gelpi, Josep Lluis/0000-0002-0566-7723; Guigo, Roderic/0000-0002-5738-4477; Hubbard, Tim/0000-0002-1767-9318; Foissac, Sylvain/0000-0002-2631-5356; Valencia, Alfonso/0000-0002-8937-6789; Lacroix, Vincent/0000-0002-4235-8524; Gingeras, Thomas/0000-0001-9106-3573; Orozco Lopez, Modesto/0000-0002-8608-3278; Salehi-Ashtiani, Kourosh/0000-0002-6521-5243 FU National Human Genome Research for the ENCODE [U01HG003150, U01HG003147]; Spanish Ministry of Education and Science; Ellison Foundation; Dana Farber Cancer Institute Strategic Initiative; Swiss National Science Foundation; European Commission; National Center of Excellence; ChildCare Foundation; European Union; Wellcome Trust; Spanish Ministry of Science [CTQ2005-09365-C02-02, BIO2009-10964]; Instituto Nacional de Bioinformatica; Consolider E-science project [CSD2007-00050]; COMBIOMED RETICS; Fundacion Marcelino Botin; National Institutes of Health [HG003143, U54 HG004592]; Consolider E-Science [CSD2007-00050]; Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium); NHGRI [U54HG004557]; W.M. Keck Foundation; Affymetrix Inc. FX This work has been supported by grants U01HG003150 and U01HG003147 from the National Human Genome Research for the ENCODE project (http://www.genome.gov/10005107) to RG (CRG, Lausanne and Geneva) and TG (Affymetrix and Cold Spring Harbor). RG was also supported by a grant from the Spanish Ministry of Education and Science (http://www.educacion.gob.es/portada.html). In addition, KS-A, RM, XY, CL, LG and MV were supported by a grant from the Ellison Foundation (http://www.ellisonfoundation.org/index.jsp) (to MV) and as Institute Sponsored Research from the Dana Farber Cancer Institute Strategic Initiative. They wish to thank Changyu Fan and Yun Shen for providing informatics support. The laboratories of SA and AR were supported by grants from the Swiss National Science Foundation (http://www.snf.ch/E/Pages/default.aspx), and the European Commission AnEUploidy Integrated Project (http://www.tigem.it/scientific-office/eu-funded-projects-1/aneuploidy). SA was also supported by the National Center of Excellence "Frontiers in Genetics" (http://www.frontiers-ingenetics.org/page.php?id=profile_en), ChildCare Foundation (http://www.projectchildcarefoundation.org/) and an ERC grant from the European Union (http://erc.europa.eu/). AF, TH and JM acknowledge support from the Wellcome Trust (http://www.wellcome.ac.uk/). The work of JLG and MO has been supported by the Spanish Ministry of Science (CTQ2005-09365-C02-02, BIO2009-10964), Instituto Nacional de Bioinformatica (http://www.inab.org/), the Consolider E-science project (CSD2007-00050), COMBIOMED RETICS and the Fundacion Marcelino Botin (http://www.fundacionmbotin.org/). JD is supported by a grant from the National Institutes of Health (HG003143) and a W.M. Keck Foundation Distinguished Young Scholar Award. JS is supported by a grant from the National Institutes of Health (U54 HG004592). The work of MT and AV was supported by Consolider E-Science (CSD2007-00050) and the Instituto Nacional de Bioinformatica (http://www.inab.org/). MV (Center for Cancer Systems Biology, CCSB) is a "Chercheur Qualifie Honoraire'' from the Fonds de la Recherche Scientifique (FRS-FNRS, French Community of Belgium). This work has also been funded by grant to TG by NHGRI (U54HG004557) (http://www.genome.gov/10005107) and partially by Affymetirix, Corp (http://www.affymetrix.com/estore/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Affymetrix manufactured the arrays used and these were purchased at the sale price agreed to in the reported grant.; The study was partially funded by Affymetrix Inc. PK, SF, IB, ED, J.Drenkow, AD and TG were employees of Affymetrix Inc. at the time of the study. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors. NR 46 TC 31 Z9 31 U1 0 U2 12 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 JAN 4 PY 2012 VL 7 IS 1 AR e28213 DI 10.1371/journal.pone.0028213 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 902VE UT WOS:000301070200004 PM 22238572 ER PT J AU Mothe, B Llano, A Ibarrondo, J Zamarreno, J Schiaulini, M Miranda, C Ruiz-Riol, M Berger, CT Herrero, MJ Palou, E Plana, M Rolland, M Khatri, A Heckerman, D Pereyra, F Walker, BD Weiner, D Paredes, R Clotet, B Felber, BK Pavlakis, GN Mullins, JI Brander, C AF Mothe, Beatriz Llano, Anuska Ibarrondo, Javier Zamarreno, Jennifer Schiaulini, Mattia Miranda, Cristina Ruiz-Riol, Marta Berger, Christoph T. Jose Herrero, M. Palou, Eduard Plana, Montse Rolland, Morgane Khatri, Ashok Heckerman, David Pereyra, Florencia Walker, Bruce D. Weiner, David Paredes, Roger Clotet, Bonaventura Felber, Barbara K. Pavlakis, George N. Mullins, James I. Brander, Christian TI CTL Responses of High Functional Avidity and Broad Variant Cross-Reactivity Are Associated with HIV Control SO PLOS ONE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; VIRAL LOAD; INFECTION; EPITOPE; GAG; LYMPHOCYTES; IMMUNE; POLYFUNCTIONALITY; IMMUNODOMINANCE AB Cytotoxic T lymphocyte (CTL) responses targeting specific HIV proteins, in particular Gag, have been associated with relative control of viral replication in vivo. However, Gag-specific CTL can also be detected in individuals who do not control the virus and it remains thus unclear how Gag-specific CTL may mediate the beneficial effects in some individuals but not in others. Here, we used a 10mer peptide set spanning HIV Gag-p24 to determine immunogen-specific T-cell responses and to assess functional properties including functional avidity and cross-reactivity in 25 HIV-1 controllers and 25 non-controllers without protective HLA class I alleles. Our data challenge the common belief that Gag-specific T cell responses dominate the virus-specific immunity exclusively in HIV-1 controllers as both groups mounted responses of comparable breadths and magnitudes against the p24 sequence. However, responses in controllers reacted to lower antigen concentrations and recognized more epitope variants than responses in non-controllers. These cross-sectional data, largely independent of particular HLA genetics and generated using direct ex-vivo samples thus identify T cell responses of high functional avidity and with broad variant reactivity as potential functional immune correlates of relative HIV control. C1 [Mothe, Beatriz; Llano, Anuska; Ibarrondo, Javier; Zamarreno, Jennifer; Schiaulini, Mattia; Ruiz-Riol, Marta; Paredes, Roger; Clotet, Bonaventura; Brander, Christian] Hosp Badalona Germans Trias & Pujol, IrsiCaixa AIDS Res Inst HIVACAT, Barcelona, Spain. [Mothe, Beatriz; Miranda, Cristina; Paredes, Roger; Clotet, Bonaventura] Hosp Badalona Germans Trias & Pujol, Lluita Sida Fdn, Barcelona, Spain. [Mothe, Beatriz; Schiaulini, Mattia] Univ Autonoma Barcelona, E-08193 Barcelona, Spain. [Berger, Christoph T.; Pereyra, Florencia; Walker, Bruce D.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA. [Jose Herrero, M.; Palou, Eduard] Hosp Badalona Germans Trias & Pujol, Dept Immunol, LIRAD Banc Sang & Teixits, Barcelona, Spain. [Plana, Montse] Univ Barcelona, HIVACAT, Hosp Clin, AIDS Res Grp IDIBAPS, Barcelona, Spain. [Rolland, Morgane; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Khatri, Ashok] Massachusetts Gen Hosp, Peptide Prot Core Facil, Boston, MA 02114 USA. [Heckerman, David] Microsoft Res, Redmond, WA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Weiner, David] Univ Penn, Philadelphia, PA 19104 USA. [Felber, Barbara K.; Pavlakis, George N.] NCI Frederick, Frederick, MD USA. [Brander, Christian] ICREA, Barcelona, Spain. RP Mothe, B (reprint author), Hosp Badalona Germans Trias & Pujol, IrsiCaixa AIDS Res Inst HIVACAT, Barcelona, Spain. EM cbrander@irsicaixa.es OI Brander, Christian/0000-0002-0548-5778 FU Bill and Melinda Gates Foundation; Red de Investigacion de Sida (RIS) [RD06/04]; Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Spanish FIPSE [36-0737-09] FX This work was funded by Bill and Melinda Gates Foundation and was supported in part by the Red de Investigacion de Sida (RIS) (RD06/04), Instituto de Salud Carlos III (ISCIII), Madrid, Spain and the Spanish FIPSE 36-0737-09. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 64 Z9 64 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 JAN 4 PY 2012 VL 7 IS 1 AR e29717 DI 10.1371/journal.pone.0029717 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 902VE UT WOS:000301070200043 PM 22238642 ER PT J AU Garrison, BS Rossi, DJ AF Garrison, Brian S. Rossi, Derrick J. TI Reactive Oxygen Species Resulting from Mitochondrial Mutation Diminishes Stem and Progenitor Cell Function SO CELL METABOLISM LA English DT Editorial Material ID DNA MUTATIONS; LIMIT AB While age-dependent stem cell decline is widely recognized as being a key component of organismal aging, the underlying mechanisms remain elusive. In this issue of Cell Metabolism, Suomalainen and colleagues provide evidence that mitochondrial mutation and associated reactive oxygen species can adversely impact tissue-specific stem and progenitor cell function. C1 [Garrison, Brian S.; Rossi, Derrick J.] Harvard Univ, Stem Cell & Regenerat Biol Dept, Cambridge, MA 02138 USA. [Garrison, Brian S.; Rossi, Derrick J.] Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Garrison, Brian S.; Rossi, Derrick J.] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Rossi, DJ (reprint author), Harvard Univ, Stem Cell & Regenerat Biol Dept, Cambridge, MA 02138 USA. EM rossi@idi.harvard.edu NR 10 TC 2 Z9 2 U1 0 U2 0 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 JAN 4 PY 2012 VL 15 IS 1 BP 2 EP 3 DI 10.1016/j.cmet.2011.12.008 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 883TB UT WOS:000299656700002 PM 22225868 ER PT J AU Donmez, G Arun, A Chung, CY McLean, PJ Lindquist, S Guarente, L AF Donmez, Gizem Arun, Anirudh Chung, Chee-Yeun McLean, Pamela J. Lindquist, Susan Guarente, Leonard TI SIRT1 Protects against alpha-Synuclein Aggregation by Activating Molecular Chaperones SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PARKINSONS-DISEASE; NACP/ALPHA-SYNUCLEIN; NEURODEGENERATIVE DISEASE; CALORIE RESTRICTION; ALZHEIMERS-DISEASE; TOXICITY; STRESS; MODELS; HSP70; MICE AB alpha-Synuclein is a key molecule in the pathogenesis of synucleinopathy including dementia with Lewy bodies, Parkinson's disease, and multiple system atrophy. Sirtuins are NAD(+)-dependent protein deacetylases that are highly conserved and counter aging in lower organisms. We show that the life span of a mouse model with A53T alpha-synuclein mutation is increased by overexpressing SIRT1 and decreased by knocking out SIRT1 in brain. Furthermore, alpha-synuclein aggregates are reduced in the brains of mice with SIRT1 overexpression and increased by SIRT1 deletion. We show that SIRT1 deacetylates HSF1 (heat shock factor 1) and increases HSP70 RNA and protein levels, but only in the brains of mice with A53T and SIRT1 expression. Thus, SIRT1 responds to alpha-synuclein aggregation-induced stress by activating molecular chaperones to protect against disease. C1 [Donmez, Gizem; Arun, Anirudh; Guarente, Leonard] MIT, Paul F Glenn Lab, Cambridge, MA 02139 USA. [Donmez, Gizem; Arun, Anirudh; Guarente, Leonard] MIT, Dept Biol, Cambridge, MA 02139 USA. [McLean, Pamela J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Chung, Chee-Yeun; Lindquist, Susan] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Guarente, L (reprint author), MIT, Paul F Glenn Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM leng@mit.edu FU American Parkinson Disease Association; Johnson Johnson; NIH [NS063963]; HHMI; RJG Foundation FX This work was supported by an American Parkinson Disease Association and Johnson & Johnson postdoctoral fellowships (G.D.), NIH Grant NS063963 (P.J.M.), HHMI Collaborative Innovation Award and a grant from the RJG Foundation (S.L.), and grants from the NIH and a gift from the Glenn Foundation for Medical Research (L.G.). We are grateful to Joseph Mazzuli for advice and help with A53T alpha-synuclein-expressing H4 cells. We thank Abdullah Yalcin for comments on this manuscript. NR 32 TC 88 Z9 91 U1 3 U2 20 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 4 PY 2012 VL 32 IS 1 BP 124 EP 132 DI 10.1523/JNEUROSCI.3442-11.2012 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 876PM UT WOS:000299119700012 PM 22219275 ER PT J AU Maison, SF Liu, XP Eatock, RA Sibley, DR Grandy, DK Liberman, MC AF Maison, Stephane F. Liu, Xiao-Ping Eatock, Ruth Anne Sibley, David R. Grandy, David K. Liberman, M. Charles TI Dopaminergic Signaling in the Cochlea: Receptor Expression Patterns and Deletion Phenotypes SO JOURNAL OF NEUROSCIENCE LA English DT Article ID GUINEA-PIG COCHLEA; LATERAL OLIVOCOCHLEAR EFFERENTS; AUDITORY-NERVE FIBERS; RAT SPIRAL GANGLION; OUTER HAIR-CELLS; MOUSE COCHLEA; CAT COCHLEA; QUANTITATIVE-ANALYSIS; TYROSINE-HYDROXYLASE; SERIAL SECTIONS AB Pharmacological studies suggest that dopamine release from lateral olivocochlear efferent neurons suppresses spontaneous and sound-evoked activity in cochlear nerve fibers and helps control noise-induced excitotoxicity; however, the literature on cochlear expression and localization of dopamine receptors is contradictory. To better characterize cochlear dopaminergic signaling, we studied receptor localization using immunohistochemistry or reverse transcriptase PCR and assessed histopathology, cochlear responses and olivocochlear function in mice with targeted deletion of each of the five receptor subtypes. In normal ears, D1, D2, and D5 receptors were detected in microdissected immature (postnatal days 10-13) spiral ganglion cells and outer hair cells but not inner hair cells. D4 was detected in spiral ganglion cells only. In whole cochlea samples from adults, transcripts for D1, D2, D4, and D5 were present, whereas D3 mRNA was never detected. D1 and D2 immunolabeling was localized to cochlear nerve fibers, near the first nodes of Ranvier (D2) and in the inner spiral bundle region (D1 and D2) where presynaptic olivocochlear terminals are found. No other receptor labeling was consistent. Cochlear function was normal in D3, D4, and D5 knock-outs. D1 and D2 knock-outs showed slight, but significant enhancement and suppression, respectively, of cochlear responses, both in the neural output [auditory brainstem response (ABR) wave 1] and in outer hair cell function [distortion product otoacoustic emissions (DPOAEs)]. Vulnerability to acoustic injury was significantly increased in D2, D4 and D5 lines: D1 could not be tested, and no differences were seen in D3 mutants, consistent with a lack of receptor expression. The increased vulnerability in D2 knock-outs was seen in DPOAEs, suggesting a role for dopamine in the outer hair cell area. In D4 and D5 knock-outs, the increased noise vulnerability was seen only in ABRs, consistent with a role for dopaminergic signaling in minimizing neural damage. C1 [Maison, Stephane F.; Liu, Xiao-Ping; Eatock, Ruth Anne; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Maison, Stephane F.; Eatock, Ruth Anne; Liberman, M. Charles] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Maison, Stephane F.; Liu, Xiao-Ping; Eatock, Ruth Anne; Liberman, M. Charles] Harvard MIT, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 USA. [Sibley, David R.] Natl Inst Neurol Disorders & Stroke, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. [Grandy, David K.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM stephane_maison@meei.harvard.edu RI Eatock, Ruth/F-6404-2013; OI Eatock, Ruth Anne/0000-0001-7547-2051 FU National Institutes of Health [R01 DC0188, R01 DC02290, P30 DC5029] FX This work was supported by National Institutes of Health Grants R01 DC0188 (M. C. L.), R01 DC02290 (R. A. E.), and P30 DC5029 (M. C. L.). We are indebted to Dr. Malcolm Low for his help in guiding us to sources for DR knock-out lines. We thank Ben Winterroth for setting up the protocol used to amplify messenger RNA from small numbers of cells. The skillful assistance of Leslie Dodds and Constance Miller is gratefully acknowledged. NR 58 TC 20 Z9 21 U1 2 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 4 PY 2012 VL 32 IS 1 BP 344 EP 355 DI 10.1523/JNEUROSCI.4720-11.2012 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 876PM UT WOS:000299119700032 PM 22219295 ER PT J AU Blumenthal, D AF Blumenthal, David TI A Physician Goes to Washington ... and Safely Returns SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM dblumenthal@partners.org NR 0 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 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 4 PY 2012 VL 307 IS 1 BP 45 EP 46 DI 10.1001/jama.2011.1899 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 872ET UT WOS:000298792300020 PM 22215164 ER PT J AU Li, ZP Heber, D AF Li, Zhaoping Heber, David TI Overeating and Overweight Extra Calories Increase Fat Mass While Protein Increases Lean Mass SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID OBESITY C1 [Heber, David] VA Greater Los Angeles Hlth Care Syst, Ctr Human Nutr, Los Angeles, CA 90095 USA. [Li, Zhaoping; Heber, David] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Heber, D (reprint author), VA Greater Los Angeles Hlth Care Syst, Ctr Human Nutr, 900 Vet Ave, Los Angeles, CA 90095 USA. EM dheber@mednet.ucla.edu NR 19 TC 6 Z9 6 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 4 PY 2012 VL 307 IS 1 BP 86 EP 87 DI 10.1001/jama.2011.1959 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 872ET UT WOS:000298792300026 PM 22215169 ER PT J AU Valencia, A Sapp, E Reeves, PB Alexander, J Masso, N Li, XY Kegel, KB DiFiglia, M AF Valencia, Antonio Sapp, Ellen Reeves, Patrick B. Alexander, Jonathan Masso, Nicholas Li, Xueyi Kegel, Kimberly B. DiFiglia, Marian TI Reagents that block neuronal death from Huntington's disease also curb oxidative stress SO NEUROREPORT LA English DT Article DE brain derived neurotropic factor; glycogen synthase kinase 3-beta; mutant huntingtin; N-acetyl-cysteine; neurodegeneration; reactive oxygen species ID IN MOUSE MODEL; EXPRESSING MUTANT HUNTINGTIN; EARLY MOTOR; CELL-DEATH; MICE; DAMAGE; DEFICITS; RECEPTOR; BRAIN; BDNF AB Patients with Huntington's disease suffer severe neuronal loss and signs of oxidative damage in the brain. Previously we found that primary neurons from embryonic cortex of mice bearing the Huntington's disease mutation (140 glutamines inserted into exon 1 of huntingtin) showed higher levels of reactive oxygen species before cell death. Here, we treated mutant neurons with known neuroprotective agents and determined the effects on neuronal survival and levels of reactive oxygen species. Primary neurons were exposed to the neurotrophin, brain derived neurotrophic factor, the antioxidant N-acetylcysteine or a specific inhibitor of glycogen synthase kinase 3-beta, SB216763. Each reagent increased the survival of the mutant neurons compared with untreated mutant neurons and also reduced the levels of reactive oxygen species to levels of wild-type neurons. These results suggest that reducing the levels of reactive oxygen species may be necessary to protect neurons with the Huntington's disease mutation from cell death. NeuroReport 23: 10-15 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP DiFiglia, M (reprint author), Massachusetts Gen Hosp E, Dept Neurol, 114 16th St,Room 2002, Charlestown, MA 02129 USA. EM difiglia@helix.mgh.harvard.edu FU Hereditary Disease Foundation [2008A051302]; Fundacion Mexico en Harvard A.C. FX This study was supported by the Hereditary Disease Foundation; Grant number 2008A051302 to A.V. and the Fundacion Mexico en Harvard A.C. (to A.V.). NR 22 TC 8 Z9 8 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 4 PY 2012 VL 23 IS 1 BP 10 EP 15 DI 10.1097/WNR.0b013e32834d92e6 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 862ZM UT WOS:000298132600003 PM 22045254 ER PT J AU Shen, KZ Johnson, SW AF Shen, Ke-Zhong Johnson, Steven W. TI Gamma-aminobutyric acid(B) receptor activation suppresses stimulus-evoked burst firing in rat substantia nigra reticulata neurons SO NEUROREPORT LA English DT Article DE baclofen; brain slice; burst firing; complex excitatory postsynaptic currents; gamma-aminobutyric acid(B); substantia nigra reticulata; subthalamic nucleus ID SUBTHALAMIC NUCLEUS; PARKINSONS-DISEASE; BASAL GANGLIA; COMPLEX EPSCS; GABA-B; STIMULATION; TRANSMISSION; APOMORPHINE; LESIONS AB Previous whole-cell patch-pipette studies showed that focal electrical stimulation of the subthalamic nucleus (STN) evokes a long-lasting complex excitatory postsynaptic currents (EPSC) and synaptically evoked bursts of action potentials in substantia nigra pars reticulata (SNR) neurons. Although synaptically evoked bursting may play a role in normal physiology, excessive burst firing correlates with symptoms of Parkinson's disease. We used patch-pipette recordings in rat brain slices to study the effects of baclofen on complex EPSCs and STN-induced burst firing in SNR neurons. Baclofen (1 mu M) caused a reversible, 73% reduction in complex EPSCs, and this effect was blocked by the gamma-aminobutyric acid(B) antagonist CGP35348 (100 mu M). Using the loose-patch method to record extracellular potentials, a lower concentration of baclofen (100 nM) inhibited STN-evoked bursts, while leaving spontaneous firing of action potentials less affected. We suggest that strategies that selectively inhibit burst firing in the SNR might have therapeutic potential in the treatment of Parkinson's disease. NeuroReport 23:40-44 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Shen, Ke-Zhong; Johnson, Steven W.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Johnson, Steven W.] Portland VA Med Ctr, Portland, OR USA. RP Johnson, SW (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. EM johnsost@ohsu.edu FU United States Public Health Service [NS38715, NS060662]; Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center FX this work was supported by United States Public Health Service Grants NS38715 and NS060662, and the Portland Veterans Affairs Parkinson's Disease Research, Education, and Clinical Center. NR 25 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 4 PY 2012 VL 23 IS 1 BP 40 EP 44 DI 10.1097/WNR.0b013e32834e4899 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 862ZM UT WOS:000298132600009 PM 22127013 ER PT J AU Greenstein, RJ Su, LY Brown, ST AF Greenstein, Robert J. Su, Liya Brown, Sheldon T. TI Vitamins A & D Inhibit the Growth of Mycobacteria in Radiometric Culture SO PLOS ONE LA English DT Article ID AVIUM SUBSPECIES PARATUBERCULOSIS; CROHNS-DISEASE; IN-VITRO; TUBERCULOSIS; DRUGS; SUSCEPTIBILITY; 6-MERCAPTOPURINE; CYCLOSPORINE; RESISTANCE; INFECTION AB Background: The role of vitamins in the combat of disease is usually conceptualized as acting by modulating the immune response of an infected, eukaryotic host. We hypothesized that some vitamins may directly influence the growth of prokaryotes, particularly mycobacteria. Methods: The effect of four fat-soluble vitamins was studied in radiometric Bactec (R) culture. The vitamins were A (including a precursor and three metabolites,) D, E and K. We evaluated eight strains of three mycobacterial species (four of M. avium subspecies paratuberculosis (MAP), two of M. avium and two of M. tb. complex). Principal Findings: Vitamins A and D cause dose-dependent inhibition of all three mycobacterial species studied. Vitamin A is consistently more inhibitory than vitamin D. The vitamin A precursor, beta-carotene, is not inhibitory, whereas three vitamin A metabolites cause inhibition. Vitamin K has no effect. Vitamin E causes negligible inhibition in a single strain. Significance: We show that vitamin A, its metabolites Retinyl acetate, Retinoic acid and 13-cis Retinoic acid and vitamin D directly inhibit mycobacterial growth in culture. These data are compatible with the hypothesis that complementing the immune response of multicellular organisms, vitamins A and D may have heretofore unproven, unrecognized, independent and probable synergistic, direct antimycobacterial inhibitory activity. C1 [Greenstein, Robert J.] James J Peters Vet Affairs Med Ctr, Dept Surg, Bronx, NY USA. [Greenstein, Robert J.; Su, Liya] James J Peters Vet Affairs Med Ctr, Lab Mol Surg Res, Bronx, NY USA. [Brown, Sheldon T.] James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. [Brown, Sheldon T.] Mt Sinai Sch Med, New York, NY USA. RP Greenstein, RJ (reprint author), James J Peters Vet Affairs Med Ctr, Dept Surg, Bronx, NY USA. EM BGAxis@aol.com FU Becton-Dickinson FX This project was extramurally funded by Becton-Dickinson, whose sole contribution was to provide the authors with the culture medium used in these experiments. Intramural funds were from the Bronx Veterans Medical Research Foundation, Inc. a charity at the James J. Peters VAMC Bronx NY. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 8 Z9 8 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 3 PY 2012 VL 7 IS 1 AR e29631 DI 10.1371/journal.pone.0029631 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903NK UT WOS:000301123400076 PM 22235314 ER PT J AU Mao, PZ Meshul, CK Thuillier, P Goldberg, NRS Reddy, PH AF Mao, Peizhong Meshul, Charles K. Thuillier, Philippe Goldberg, Natalie R. S. Reddy, P. Hemachandra TI CART Peptide Is a Potential Endogenous Antioxidant and Preferentially Localized in Mitochondria SO PLOS ONE LA English DT Article ID AMPHETAMINE-REGULATED TRANSCRIPT; PARKINSONS-DISEASE; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; BODY-WEIGHT; MESOLIMBIC DOPAMINE; NUCLEUS-ACCUMBENS; MESSENGER-RNA; DNA-DAMAGE; COCAINE AB The multifunctional neuropeptide Cocaine and Amphetamine Regulated Transcript (CART) is secreted from hypothalamus, pituitary, adrenal gland and pancreas. It also can be found in circulatory system. This feature suggests a general role for CART in different cells. In the present study, we demonstrate that CART protects mitochondrial DNA (mtDNA), cellular proteins and lipids against the oxidative action of hydrogen peroxide, a widely used oxidant. Using cis-parinaric acid as a sensitive reporting probe for peroxidation in membranes, and a lipid-soluble azo initiator of peroxyl radicals, 2,2'-Azobis(2,4-dimethylvaleronitrile) we found that CART is an antioxidant. Furthermore, we found that CART localized to mitochondria in cultured cells and mouse brain neuronal cells. More importantly, pretreatment with CART by systemic injection protects against a mouse oxidative stress model, which mimics the main features of Parkinson's disease. Given the unique molecular structure and biological features of CART, we conclude that CART is an antioxidant peptide (or antioxidant hormone). We further propose that it may have strong therapeutic properties for human diseases in which oxidative stress is strongly involved such as Parkinson's disease. C1 [Mao, Peizhong; Reddy, P. Hemachandra] Oregon Hlth & Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Mao, Peizhong; Thuillier, Philippe] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Mao, Peizhong; Thuillier, Philippe] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Meshul, Charles K.; Goldberg, Natalie R. S.] Portland VA Med Ctr, Res Serv, Portland, OR USA. [Meshul, Charles K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Meshul, Charles K.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Reddy, P. Hemachandra] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. RP Mao, PZ (reprint author), Oregon Hlth & Sci Univ, Div Neurosci, Oregon Natl Primate Res Ctr, Beaverton, OR USA. EM maop@ohsu.edu FU American Heart Association [0565527Z]; Department of Veterns Affairs; National Institutes of Health [CA112083-01, AG028072, AG026051, RR000163] FX These studies were supported by the American Heart Association (Beginning Grant-in-Aid 0565527Z) to PM, the Department of Veterns Affairs Merit Review Program to CK, and the National Institutes of Health to PT (CA112083-01) and to PHR (AG028072, AG026051), and to ONPRC (RR000163). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 74 TC 18 Z9 18 U1 0 U2 7 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 JAN 3 PY 2012 VL 7 IS 1 AR e29343 DI 10.1371/journal.pone.0029343 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903NK UT WOS:000301123400048 PM 22235287 ER PT J AU Velinov, M Dolzhanskaya, N Gonzalez, M Powell, E Konidari, I Hulme, W Staropoli, JF Xin, WN Wen, GY Barone, R Coppel, SH Sims, K Brown, WT Zuchner, S AF Velinov, Milen Dolzhanskaya, Natalia Gonzalez, Michael Powell, Eric Konidari, Ioanna Hulme, William Staropoli, John F. Xin, Winnie Wen, Guang Y. Barone, Rosemary Coppel, Scott H. Sims, Katherine Brown, W. Ted Zuechner, Stephan TI Mutations in the Gene DNAJC5 Cause Autosomal Dominant Kufs Disease in a Proportion of Cases: Study of the Parry Family and 8 Other Families SO PLOS ONE LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; FORM AB Background: The Neuronal Ceroid Lipofuscinoses (NCL) comprise at least nine progressive neurodegenerative genetic disorders. Kufs disease, an adult-onset form of NCL may be recessively or dominantly inherited. Our study aimed to identify genetic mutations associated with autosomal dominant Kufs disease (ADKD). Methodology and Principal Findings: We have studied the family first reported with this phenotype in the 1970s, the Parry family. The proband had progressive psychiatric manifestations, seizures and cognitive decline starting in her mid 20 s. Similarly affected relatives were observed in seven generations. Several of the affected individuals had post-mortem neuropathological brain study confirmatory for NCL disease. We conducted whole exome sequencing of three affected family members and identified a pLeu116del mutation in the gene DNAJC5, which segregated with the disease phenotype. An additional eight unrelated affected individuals with documented autosomal dominant or sporadic inheritance were studied. All had diagnostic confirmation with neuropathological studies of brain tissue. Among them we identified an additional individual with a p. Leu115Arg mutation in DNAJC5. In addition, a pAsn477Ser change in the neighboring gene PRPF6, a gene previously found to be associated with retinitis pigmentosa, segregated with the ADKD phenotype. Interestingly, two individuals of the Parry family did report visual impairment. Conclusions: Our study confirmed the recently reported association of DNAJC5 mutations with ADKD in two out of nine well-defined families. Sequence changes in PRPF6 have not been identified in other unrelated cases. The association of vision impairment with the expected PRPF6 dysfunction remains possible but would need further clinical studies in order to confirm the co-segregation of the visual impairment with this sequence change. C1 [Velinov, Milen; Dolzhanskaya, Natalia; Wen, Guang Y.; Brown, W. Ted] New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. [Velinov, Milen] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. [Gonzalez, Michael; Powell, Eric; Konidari, Ioanna; Hulme, William; Zuechner, Stephan] Univ Miami, Miller Sch Med, Hussman Inst Human Genet, Miami, FL 33136 USA. [Staropoli, John F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Staropoli, John F.; Xin, Winnie; Barone, Rosemary; Coppel, Scott H.; Sims, Katherine] Massachusetts Gen Hosp, Dept Neurol, Neurogenet DNA Diagnost Lab, Ctr Human Genet Res, Boston, MA 02114 USA. [Staropoli, John F.; Sims, Katherine] Harvard Univ, Sch Med, Boston, MA USA. RP Velinov, M (reprint author), New York State Inst Basic Res Dev Disabil, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA. EM milen.velinov@opwdd.ny.gov OI Wen, Guang Gary/0000-0001-6844-7528 FU New York State Office of People with Developmental Disabilities, Batten Disease Support and Research Association; National Institute of Neurological Disorders and Stroke [RO1-NS072248, RO1NS054132] FX Funding provided by the New York State Office of People with Developmental Disabilities, Batten Disease Support and Research Association and the National Institute of Neurological Disorders and Stroke (RO1-NS072248, RO1NS054132 to SZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 9 TC 38 Z9 41 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 3 PY 2012 VL 7 IS 1 AR e29729 DI 10.1371/journal.pone.0029729 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903NK UT WOS:000301123400095 PM 22235333 ER PT J AU Yamamura, S Saini, S Majid, S Hirata, H Ueno, K Deng, G Dahiya, R AF Yamamura, Soichiro Saini, Sharanjot Majid, Shahana Hirata, Hiroshi Ueno, Koji Deng, Guoren Dahiya, Rajvir TI MicroRNA-34a Modulates c-Myc Transcriptional Complexes to Suppress Malignancy in Human Prostate Cancer Cells SO PLOS ONE LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; RECRUITS P-TEFB; RHO-GTPASES; TUMOR-SUPPRESSOR; GENE-EXPRESSION; DNA-REPLICATION; DOWN-REGULATION; CAD PROMOTER; MET RECEPTOR; IN-VIVO AB MicroRNA-34a (miR-34a), a potent mediator of tumor suppressor p53, has been reported to function as a tumor suppressor and miR-34a was found to be downregulated in prostate cancer tissues. We studied the functional effects of miR-34a on c-Myc transcriptional complexes in PC-3 prostate cancer cells. Transfection of miR-34a into PC-3 cells strongly inhibited in vitro cell proliferation, cell invasion and promoted apoptosis. Transfection of miR-34a into PC-3 cells also significantly inhibited in vivo xenograft tumor growth in nude mice. miR-34a downregulated expression of c-Myc oncogene by targeting its 39 UTR as shown by luciferase reporter assays. miR-34a was found to repress RhoA, a regulator of cell migration and invasion, by suppressing c-Myc-Skp2-Miz1 transcriptional complex that activates RhoA. Overexpression of c-Myc reversed miR-34a suppression of RhoA expression, suggesting that miR-34a inhibits invasion by suppressing RhoA through c-Myc. miR-34a was also found to repress c-Myc-pTEFB transcription elongation complex, indicating one of the mechanisms by which miR-34a has profound effects on cellular function. This is the first report to document that miR-34a suppresses assembly and function of the c-Myc-Skp2-Miz1 complex that activates RhoA and the c-Myc-pTEFB complex that elongates transcription of various genes, suggesting a novel role of miR-34a in the regulation of transcription by c-Myc complex. C1 [Yamamura, Soichiro] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Yamamura, S (reprint author), San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. EM rdahiya@urology.ucsf.edu FU NIH [R01CA138642, T32DK007790] FX This study was supported by Grants R01CA138642, T32DK007790 (NIH), VA Research Enhancement Award Program (REAP) and Merit Review grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 51 TC 59 Z9 63 U1 2 U2 10 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 JAN 3 PY 2012 VL 7 IS 1 AR e29722 DI 10.1371/journal.pone.0029722 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 903NK UT WOS:000301123400094 PM 22235332 ER PT J AU Cervantes, TM Slocum, AH Seldin, EB AF Cervantes, Thomas M. Slocum, Alexander H., Jr. Seldin, Edward B. TI Design and experimental evaluation of adjustable bone plates for mandibular fracture fixation SO JOURNAL OF BIOMECHANICS LA English DT Article DE Bone plate; Malocclusion; Compliant structure ID ANGLE FRACTURES; PLATING TECHNIQUES; INTERNAL-FIXATION; STRENGTH; REPAIR AB Conventional bone plates are commonly used for surgical mandibular fracture fixation. Improper alignment between bone segments, however, can result in malocclusion. Current methods of fixation require a surgeon to visually align segments of bone and affix a metal plate using bone screws, after which little can be done to adjust alignment. A method of adjusting fracture alignment after plate placement, without screw removal, presents an improvement over costly and risky revision surgery. A modified bone plate has been designed with a deformable section to give surgeons the ability to reduce misalignments at the fracture site. The mechanics of deformation for various adjustment mechanisms was explored analytically, numerically, and experimentally to ensure that the adjustable plate is comparable to conventional bone plates. A static force of 358.8 N is required to deform the adjustable bone plate, compared with predicted values of 351 N using numerical simulation and 362 N using a simple beam theory. Dynamic testing was performed to simulate in vivo loading conditions and evaluate load-capacity in both deformed and un-deformed bone plates. Results indicate that bending stiffness of a rectangular bone plate is 709 N/mm, compared with 174 N/mm for an octagonal plate and 176 N/mm for standard plates. Once deformed, the rectangular and octagonal plates had a stiffness of 323 N/mm and 228 N/mm, respectively. Un-deformed and deformed adjustable bone plates have efficacy in bone segment fixation and healing. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Cervantes, Thomas M.; Slocum, Alexander H., Jr.] MIT, Dept Mech Engn, Cambridge, MA 02139 USA. [Seldin, Edward B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Slocum, AH (reprint author), MIT, Dept Mech Engn, Cambridge, MA 02139 USA. EM ahslocum@mit.edu FU CIMIT FX The authors are grateful to CIMIT for funding this work in part; to Pierce Hayward for help with bone plate testing; the PERG lab for use of facilities; Ken Stone and Hayami Arakawa at the MIT Hobby Shop for Waterjet support; Mark Belanger at the MIT Edgerton Student Shop and Bill Buckley and Pat McAtemny at the LMP Machine Shop for fabrication assistance and hardware; and Sarah Southerland for assistance with preparation of image figures. NR 25 TC 1 Z9 1 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD JAN 3 PY 2012 VL 45 IS 1 BP 172 EP 178 DI 10.1016/j.jbiomech.2011.09.010 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 880ZG UT WOS:000299448500023 PM 22036033 ER PT J AU Murphy, TP Cutlip, DE Regensteiner, JG Mohler, ER Cohen, DJ Reynolds, MR Massaro, JM Lewis, BA Cerezo, J Oldenburg, NC Thum, CC Goldberg, S Jaff, MR Steffes, MW Comerota, AJ Ehrman, J Treat-Jacobson, D Walsh, ME Collins, T Badenhop, DT Bronas, U Hirsch, AT AF Murphy, Timothy P. Cutlip, Donald E. Regensteiner, Judith G. Mohler, Emile R. Cohen, David J. Reynolds, Matthew R. Massaro, Joseph M. Lewis, Beth A. Cerezo, Joselyn Oldenburg, Niki C. Thum, Claudia C. Goldberg, Suzanne Jaff, Michael R. Steffes, Michael W. Comerota, Anthony J. Ehrman, Jonathan Treat-Jacobson, Diane Walsh, M. Eileen Collins, Tracie Badenhop, Dalynn T. Bronas, Ulf Hirsch, Alan T. CA CLEVER Study Investigators TI Supervised Exercise Versus Primary Stenting for Claudication Resulting From Aortoiliac Peripheral Artery Disease Six-Month Outcomes From the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) Study SO CIRCULATION LA English DT Article DE claudication; comparative effectiveness research; peripheral artery disease; vascular diseases ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; INTERMITTENT CLAUDICATION; ENDOVASCULAR REVASCULARIZATION; FUNCTIONAL STATUS; LOWER-EXTREMITY; LONG; ANGIOPLASTY; PERFORMANCE; PLACEMENT AB Background-Claudication is a common and disabling symptom of peripheral artery disease that can be treated with medication, supervised exercise (SE), or stent revascularization (ST). Methods and Results-We randomly assigned 111 patients with aortoiliac peripheral artery disease to receive 1 of 3 treatments: optimal medical care (OMC), OMC plus SE, or OMC plus ST. The primary end point was the change in peak walking time on a graded treadmill test at 6 months compared with baseline. Secondary end points included free-living step activity, quality of life with the Walking Impairment Questionnaire, Peripheral Artery Questionnaire, Medical Outcomes Study 12-Item Short Form, and cardiovascular risk factors. At the 6-month follow-up, change in peak walking time (the primary end point) was greatest for SE, intermediate for ST, and least with OMC (mean change versus baseline, 5.8 +/- 4.6, 3.7 +/- 4.9, and 1.2 +/- 2.6 minutes, respectively; P < 0.001 for the comparison of SE versus OMC, P = 0.02 for ST versus OMC, and P = 0.04 for SE versus ST). Although disease-specific quality of life as assessed by the Walking Impairment Questionnaire and Peripheral Artery Questionnaire also improved with both SE and ST compared with OMC, for most scales, the extent of improvement was greater with ST than SE. Free-living step activity increased more with ST than with either SE or OMC alone (114 +/- 274 versus 73 +/- 139 versus -6 +/- 109 steps per hour), but these differences were not statistically significant. Conclusions-SE results in superior treadmill walking performance than ST, even for those with aortoiliac peripheral artery disease. The contrast between better walking performance for SE and better patient-reported quality of life for ST warrants further study. C1 [Murphy, Timothy P.] Rhode Isl Hosp, Vasc Dis Res Ctr, Providence, RI 02903 USA. [Cutlip, Donald E.; Reynolds, Matthew R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Cutlip, Donald E.; Reynolds, Matthew R.; Thum, Claudia C.] Harvard Clin Res Inst, Boston, MA USA. [Regensteiner, Judith G.] Univ Colorado, Sch Med, Aurora, CO USA. [Mohler, Emile R.] Univ Penn, Philadelphia, PA 19104 USA. [Cohen, David J.] Univ Missouri, Kansas City, KS USA. [Massaro, Joseph M.] Boston Univ, Boston, MA 02215 USA. [Lewis, Beth A.] Univ Minnesota, Sch Kinesiol, Minneapolis, MN USA. [Oldenburg, Niki C.; Steffes, Michael W.; Collins, Tracie; Hirsch, Alan T.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Goldberg, Suzanne] NHLBI, Bethesda, MD 20892 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Comerota, Anthony J.] Jobst Vasc Ctr, Toledo, OH USA. Henry Ford Hosp, Detroit, MI 48202 USA. [Treat-Jacobson, Diane; Bronas, Ulf] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [Walsh, M. Eileen] Univ Toledo, Coll Nursing, Toledo, OH 43606 USA. RP Murphy, TP (reprint author), Rhode Isl Hosp, Vasc Dis Res Ctr, Gerry 337,593 Eddy St, Providence, RI 02903 USA. EM tmurphy@lifespan.org OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute [HL77221, HL081656]; Cordis/Johnson & Johnson (Warren, NJ); eV3 (Plymouth, MN); Boston Scientific (Natick, MA); Abbott Vascular; Cordis/Johnson Johnson; Otsuka Pharmaceuticals; Microvention/Terumo, Inc.; Medtronic; Boston Scientific; Medrad; Medtronic, Inc.; Aastrom; Baxter; BMS; Boehringer Ingelheim; BSN; Colorado Prevention Center; CVRx; Daiichi Sankyo; EV3; Johnson Johnson; Lombard Medical; National Institutes of Health; Pfizer; Sanofi/Aventis; Schering Plough; Talecris; National Heart, Lung, and Blood Institute; Cytokinetics; Viromed; Merck; Pozen; Novartis; AstraZeneca FX The CLEVER study was sponsored mostly by the National Heart, Lung, and Blood Institute (grants HL77221 and HL081656) and received financial support from Cordis/Johnson & Johnson (Warren, NJ), eV3 (Plymouth, MN), and Boston Scientific (Natick, MA). Otsuka America, Inc, (San Francisco, CA) donated cilostazol for all study participants throughout the study. Omron Healthcare Inc, Lake Forest, IL, donated pedometers. Krames Staywell, San Bruno, CA, donated print materials for study participants on exercise and diet.; Dr Murphy has received research grant support from Abbott Vascular, Cordis/Johnson & Johnson, and Otsuka Pharmaceuticals and consultant fees from Microvention/Terumo, Inc. Dr Cohen has received research grant support from Medtronic, Boston Scientific, Abbott Vascular, and Medrad and consultant fees from Medtronic, Inc. Dr Reynolds has received consultant fees from Medtronic, Inc. Dr Jaff has equity in Micell, Inc and PQ Bypass; has board membership at VIVA Physicians, Inc; and is a consultant for Becker Venture Services Group, Abbott Vascular, Cordis Corp, Covidien/eV3, and Medtronic Vascular. Dr Comerota serves on the advisory committee for BMS Aastrom, Covidien, AngioDynamics, Otsuka, Convatec, Sanofi/Aventis, Cook, Inc, Servier, ZymoGenetics, and Vessix Vascular (formerly Minnow Medical); has been a consultant to Aastrom, AngioDynamics, Convatec, Cook, Covidien, BMS, Sanofi/Aventis, and Talecris; and has received grant/research support from Aastrom, Abbott Vascular, Baxter, BMS, Boehringer Ingelheim, BSN, Colorado Prevention Center, CVRx, Daiichi Sankyo, EV3, Johnson & Johnson, Lombard Medical, Medtronic, National Institutes of Health, Pfizer, Sanofi/Aventis, Schering Plough, and Talecris. Dr Treat-Jacobson has received research grant support from the National Heart, Lung, and Blood Institute/Exercise Training for Claudication: Arm Ergometry Versus Treadmill Walking Study. Dr Collins has been a Data Safety Monitoring Board member for Viromed BioPharma/Synteract. Dr Hirsch has received research grant support from Cytokinetics, Viromed, and Abbott Vascular and consultant fees from Merck, Pozen, Novartis, and AstraZeneca. The other authors report no conflicts. NR 34 TC 143 Z9 146 U1 4 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 3 PY 2012 VL 125 IS 1 BP 130 EP 139 DI 10.1161/CIRCULATIONAHA.111.075770 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 877HT UT WOS:000299169100026 PM 22090168 ER PT J AU Yu, Z Liu, N Wang, Y Li, X Wang, X AF Yu, Z. Liu, N. Wang, Y. Li, X. Wang, X. TI IDENTIFICATION OF NEUROGLOBIN-INTERACTING PROTEINS USING YEAST TWO-HYBRID SCREENING SO NEUROSCIENCE LA English DT Article DE neuroglobin; yeast two-hybrid screening; molecular interaction ID HYPOXIA REOXYGENATION INJURY; PERMEABILITY TRANSITION PORE; MESSENGER-RNA; NITRIC-OXIDE; GLUCOSE DEPRIVATION; OXIDATIVE STRESS; LIGAND-BINDING; CYTOCHROME-C; BCL-2 FAMILY; MOUSE-BRAIN AB Neuroglobin (Ngb) is a globin protein that is highly and specifically expressed in brain neurons. A large volume of evidence has proven that Ngb is a neuroprotective molecule against hypoxic/ischemic brain injury and other related neurological disorder; however, the underlying mechanisms remain poorly understood. Aiming to provide more clues in understanding the molecular mechanisms of Ngb's neuro-protection, we performed yeast two-hybrid screening to search for proteins that interact with Ngb. From a mouse brain cDNA library, we found totally 36 proteins that potentially interact with Ngb, and 10 of them were each identified in multiple positive clones. The shared sequences within these multiple clones are more likely to be Ngb-interacting domains. In primary cultured mouse cortical neurons, immuno-precipitation was performed to confirm the interactions of selected proteins with Ngb. The discovered Ngb-interacting proteins in this study include those involved in energy metabolism, mitochondria function, and signaling pathways for cell survival and proliferation. Our findings provide molecular targets for investigating protein interaction-based biological functions and neuroprotective mechanisms of Ngb. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Yu, Z.; Liu, N.; Wang, X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA USA. [Yu, Z.; Liu, N.; Wang, X.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA. [Yu, Z.; Liu, N.; Wang, X.] Harvard Univ, Program Neurosci, Charlestown, MA USA. [Wang, Y.; Li, X.] Wenzhou Med Coll, Sch Pharmaceut Sci, Wenzhou, Zhejiang, Peoples R China. RP Wang, X (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA USA. EM zyu@partners.org; wangxi@helix.mgh.harvard.edu FU NIH [R01-NS049476]; Natural Science Foundation of Zhejiang Province, China [Y2090680] FX This work was supported in part by NIH grant R01-NS049476 (to X. W.), and Natural Science Foundation of Zhejiang Province, China (Y2090680). We appreciate Dr. Eng H. Lo for his very helpful discussion. NR 53 TC 16 Z9 17 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JAN 3 PY 2012 VL 200 BP 99 EP 105 DI 10.1016/j.neuroscience.2011.10.046 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 879AO UT WOS:000299302300010 PM 22079573 ER PT J AU Qaseem, A Wilt, TJ Shekelle, P AF Qaseem, Amir Wilt, Timothy J. Shekelle, Paul TI A Clinical Practice Guideline Update on the Diagnosis and Management of Stable Chronic Obstructive Pulmonary Disease RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. [Wilt, Timothy J.] Minneapolis Vet Affairs Ctr Chron Dis Outcomes Re, Minneapolis, MN 55417 USA. [Shekelle, Paul] RAND Corp, Greater Los Angeles Vet Affairs Hlth Ctr, Santa Monica, CA 90401 USA. RP Qaseem, A (reprint author), Amer Coll Physicians, Philadelphia, PA 19106 USA. NR 5 TC 1 Z9 1 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 3 PY 2012 VL 156 IS 1 BP 69 EP 69 DI 10.7326/0003-4819-156-1-201201030-00022 PN 1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 872VK UT WOS:000298837600015 ER PT J AU Hung, WW Morrison, RS AF Hung, William W. Morrison, R. Sean TI Hip Fracture: A Complex Illness Among Complex Patients RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Hung, William W.] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Morrison, R. Sean] Mt Sinai Sch Med, New York, NY 10029 USA. RP Hung, WW (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 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 JAN 3 PY 2012 VL 156 IS 1 BP 71 EP 71 DI 10.7326/0003-4819-156-1-201201030-00028 PN 1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 872VK UT WOS:000298837600021 ER PT J AU Balko, JM Miller, TW Morrison, MM Hutchinson, K Young, C Rinehart, C Sanchez, V Jee, D Polyak, K Prat, A Perou, CM Arteaga, CL Cook, RS AF Balko, Justin M. Miller, Todd W. Morrison, Meghan M. Hutchinson, Katherine Young, Christian Rinehart, Cammie Sanchez, Violeta Jee, David Polyak, Kornelia Prat, Aleix Perou, Charles M. Arteaga, Carlos L. Cook, Rebecca S. TI The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mammary epithelial differentiation; ErbB3 ID EPIDERMAL-GROWTH-FACTOR; MAMMARY-GLAND DEVELOPMENT; DUCTAL MORPHOGENESIS; CELL; CANCER; MOUSE; EXPRESSION; HEREGULIN; ELF5; DIFFERENTIATION AB ErbB3 harbors weak kinase activity, but strongly activates downstream phosphatidylinositol 3-kinase/Akt signaling through heterodimerization with and activation by other ErbB receptor tyrosine kinases. We report here that ErbB3 loss in the luminal mammary epithelium of mice impaired Akt and MAPK signaling and reduced luminal cell proliferation and survival. ERBB3 mRNA expression levels were highest in luminal mammary populations and lowest in basal cell/stem cell populations. ErbB3 loss in mammary epithelial cells shifted gene expression patterns toward a mammary basal cell/stem cell signature. ErbB3 depletion-induced gene expression changes were rescued upon activation of Akt and MAPK signaling. Interestingly, proliferation and expansion of the mammary basal epithelium (BE) occurred upon ErbB3 targeting in the luminal epithelium, but not upon its targeting in the BE. Multiple cytokines, including interleukin 6, were induced upon ErbB3 depletion in luminal epithelium cells, which increased growth of BE cells. Taken together, these results suggest that ErbB3 regulates the balance of differentiated breast epithelial cell types by regulating their growth and survival through autocrine- and paracrine-signaling mechanisms. C1 [Miller, Todd W.; Morrison, Meghan M.; Hutchinson, Katherine; Arteaga, Carlos L.; Cook, Rebecca S.] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA. [Balko, Justin M.; Young, Christian; Rinehart, Cammie; Sanchez, Violeta; Arteaga, Carlos L.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. [Miller, Todd W.; Arteaga, Carlos L.; Cook, Rebecca S.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Breast Canc Res Program, Nashville, TN 37232 USA. [Jee, David; Polyak, Kornelia] Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02215 USA. [Polyak, Kornelia] Dana Farber Canc Inst, Boston, MA 02215 USA. [Prat, Aleix; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Prat, Aleix; Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Prat, Aleix; Perou, Charles M.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RP Cook, RS (reprint author), Vanderbilt Univ, Sch Med, Dept Canc Biol, 221 Kirkland Hall, Nashville, TN 37232 USA. EM rebecca.cook@vanderbilt.edu RI Prat, Aleix/P-8561-2014; OI Prat, Aleix/0000-0003-2377-540X; Perou, Charles/0000-0001-9827-2247 FU National Institutes of Health [R01CA143126, R01CA80195, F32CA121900, K99CA142899]; Breast Cancer Specialized Programs [P50CA98131, P50CA058223]; Vanderbilt-Ingram Cancer Center [P30CA68485]; Susan G. Komen for the Cure Grant [KG100677]; American Cancer Society [CRP-07-234]; Lee Jeans Translational Breast Cancer Research Program; Stand Up to Cancer/American Association [SU2C-AACR-DT0209] FX This work was supported by National Institutes of Health Grants R01CA143126 (to R. S. C.), R01CA80195 (to C. L. A.), and F32CA121900 and K99CA142899 (to T. W. M.); Breast Cancer Specialized Programs of Research Excellence Grants P50CA98131 (to Vanderbilt University) and P50CA058223 (to University of North Carolina-Lineberger Cancer Center); Vanderbilt-Ingram Cancer Center Support Grant P30CA68485; Susan G. Komen for the Cure Grant KG100677 (to R. S. C.); American Cancer Society Clinical Research Professorship CRP-07-234 (to C. L. A.); the Lee Jeans Translational Breast Cancer Research Program (C. L. A.); and Stand Up to Cancer/American Association for Cancer Research Dream Team Translational Cancer Research Grant SU2C-AACR-DT0209 (to C. L. A.). NR 34 TC 22 Z9 22 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 JAN 3 PY 2012 VL 109 IS 1 BP 221 EP 226 DI 10.1073/pnas.1115802109 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 873IV UT WOS:000298876500046 PM 22178756 ER PT J AU Malapaka, RRV Khoo, S Zhang, JF Choi, JH Zhou, XE Xu, Y Gong, YH Li, J Yong, EL Chalmers, MJ Chang, L Resau, JH Griffin, PR Chen, YE Xu, HE AF Malapaka, Raghu R. V. Khoo, SokKean Zhang, Jifeng Choi, Jang H. Zhou, X. Edward Xu, Yong Gong, Yinhan Li, Jun Yong, Eu-Leong Chalmers, Michael J. Chang, Lin Resau, James H. Griffin, Patrick R. Chen, Y. Eugene Xu, H. Eric TI Identification and Mechanism of 10-Carbon Fatty Acid as Modulating Ligand of Peroxisome Proliferator-activated Receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG-CHAIN TRIGLYCERIDES; WEIGHT-LOSS DIET; PPAR-GAMMA; ADIPOCYTE DIFFERENTIATION; BINDING SELECTIVITY; NUCLEAR RECEPTORS; LIPID-METABOLISM; GENE-EXPRESSION; RISK-FACTORS; OLIVE OIL AB Peroxisome proliferator-activated receptors (PPAR alpha, -beta/delta, and -gamma) are a subfamily of nuclear receptors that plays key roles in glucose and lipid metabolism. PPAR gamma is the molecular target of the thiazolidinedione class of antidiabetic drugs that has many side effects. PPAR gamma is also activated by long chain unsaturated or oxidized/nitrated fatty acids, but its relationship with the medium chain fatty acids remains unclear even though the medium chain triglyceride oils have been used to control weight gain and glycemic index. Here, we show that decanoic acid (DA), a 10-carbon fatty acid and a major component of medium chain triglyceride oils, is a direct ligand of PPAR gamma. DA binds and partially activates PPAR gamma without leading to adipogenesis. Crystal structure reveals that DA occupies a novel binding site and only partially stabilizes the AF-2 helix. DA also binds weakly to PPAR alpha and PPAR beta/delta. Treatments with DA and its triglyceride form improve glucose sensitivity and lipid profiles without weight gain in diabetic mice. Together, these results suggest that DA is a modulating ligand for PPARs, and the structure can aid in designing better and safer PPAR gamma-based drugs. C1 [Malapaka, Raghu R. V.; Zhou, X. Edward; Xu, Yong; Xu, H. Eric] Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA. [Khoo, SokKean] Van Andel Res Inst, Lab Microarray Technol, Grand Rapids, MI 49503 USA. [Khoo, SokKean; Resau, James H.] Van Andel Res Inst, Lab Analyt Cellular & Mol Microscopy, Grand Rapids, MI 49503 USA. [Zhang, Jifeng; Chang, Lin; Chen, Y. Eugene] Univ Michigan, Dept Internal Med, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Choi, Jang H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Choi, Jang H.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Gong, Yinhan; Li, Jun; Yong, Eu-Leong] Natl Univ Singapore, Dept Obstet & Gynaecol, Singapore 119228, Singapore. [Chalmers, Michael J.; Griffin, Patrick R.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA. [Xu, H. Eric] Chinese Acad Sci, VARI SIMM Ctr Drug Discovery, Ctr Struct & Funct Drug Targets, State Key Lab Drug Res,Shanghai Inst Mat Med, Shanghai 201203, Peoples R China. RP Malapaka, RRV (reprint author), Brigham & Womens Hosp, Ctr Interdisciplinary Cardiovasc Sci, 3 Blackfan Circle Dr, Boston, MA 02115 USA. EM vmalapaka@rics.bwh.harvard.edu RI Choi, Jang Hyun/B-3055-2012; Malapaka, Raghu/B-6185-2012; Gong, Yinhan/D-1932-2013 FU National Institutes of Health [DK071662, DK066202, HL089301, HL68878, HL089544]; American Heart Association [0835237N, 0840025N]; Jay and Betty Van Andel Foundation, Amway (China) Ltd. FX This work was supported, in whole or in part, by National Institutes of Health Grants DK071662 and DK066202 and HL089301 (to H. E. X.) and Grants HL68878 and HL089544 (to Y. E. C.). This work was also supported by American Heart Association Grant 0835237N (to J. Z.).; Established Investigator and supported by American Heart Association Grant 0840025N. To whom correspondence may be addressed: Cardiovascular Center, Dept. of Internal Medicine, University of Michigan, Ann Arbor, MI 48109. E-mail:echenum@med.umich.edu.; Supported by the Jay and Betty Van Andel Foundation, Amway (China) Ltd. To whom correspondence may be addressed: Laboratory of Structural Sciences, Van Andel Research Institute, Grand Rapids, MI 49503. Tel.: 616-234-5772; Fax: 616-234-5773; E-mail:eric.xu@vai.org. NR 52 TC 33 Z9 37 U1 1 U2 17 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 JAN 2 PY 2012 VL 287 IS 1 BP 183 EP 195 DI 10.1074/jbc.M111.294785 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 870PW UT WOS:000298682400020 PM 22039047 ER PT J AU Sloan, CE Champenois, K Choisy, P Losina, E Walensky, RP Schackman, BR Ajana, F Melliez, H Paltiel, AD Freedberg, KA Yazdanpanah, Y AF Sloan, Caroline E. Champenois, Karen Choisy, Philippe Losina, Elena Walensky, Rochelle P. Schackman, Bruce R. Ajana, Faiza Melliez, Hugues Paltiel, A. D. Freedberg, Kenneth A. Yazdanpanah, Yazdan CA Cost-Effectiveness Preventing AIDS TI Newer drugs and earlier treatment: impact on lifetime cost of care for HIV-infected adults SO AIDS LA English DT Article DE cost; France; HIV infection; simulation model ID EXPERIENCED HIV-1-INFECTED PATIENTS; ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; OPPORTUNISTIC INFECTIONS; GENERAL-POPULATION; TMC125 ETRAVIRINE; HIV/AIDS CARE; MEDICAL-CARE AB Objective: To determine the component costs of care to optimize treatment with limited resources. Design: We used the Cost-Effectiveness of Preventing AIDS Complications Model of HIV disease and treatment to project life expectancy and both undiscounted and discounted lifetime costs (2010 (sic)). Methods: We determined medical resource utilization among HIV-infected adults followed from 1998 to 2005 in northern France. Monthly HIV costs were stratified by CD4 cell count. Costs of CD4, HIV RNA and genotype tests and antiretroviral therapy (ART) were derived from published literature. Model inputs from national data included mean age 38 years, mean initial CD4 cell count 372 cells/mu l, ART initiation at CD4 cell counts less than 350 cells/mu l, and ART regimen costs ranging from (sic)760 to 2570 per month. Results: The model projected a mean undiscounted life expectancy of 26.5 years and a lifetime undiscounted cost of (sic)535 000/patient ((sic)320 700 discounted); 73% of costs were ART related. When patients presented to care with mean CD4 cell counts of 510 cells/mu l and initiated ART at CD4 cell counts less than 500 cells/mu l or HIV RNA more than 100 000 copies/ml, life expectancy was 27.4 years and costs increased 12%, to (sic)546 700 ((sic)324 500 discounted). When we assumed introducing generic drugs would result in a 50% decline in first-line ART costs, lifetime costs decreased 4-6%, to (sic)514 200 ((sic)302 800 discounted). Conclusion: As HIV disease is treated earlier with more efficacious drugs, survival and thus costs of care will continue to increase. The availability in high-income countries of widely used antiretroviral drugs in generic form could reduce these costs. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Sloan, Caroline E.; Champenois, Karen; Yazdanpanah, Yazdan] Univ Lille Nord France, INSERM, ATIP Avenir U995, Lille, France. [Sloan, Caroline E.; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Champenois, Karen] CNRS, LEM, Unite Mixte Rech 8179, EA 2694, Lille, France. [Choisy, Philippe; Melliez, Hugues; Yazdanpanah, Yazdan] Ctr Hosp Tourcoing, Serv Univ Malad Infectieuses & Voyageur, Tourcoing, France. [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. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.] Ctr AIDS Res, Boston, MA USA. [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Paltiel, A. D.] Yale Univ, Sch Med, New Haven, CT USA. [Yazdanpanah, Yazdan] Univ Paris Diderot, Hop Bichat Claude Bernard, Serv Malad Infectieuses & Trop, F-75877 Paris, France. RP Yazdanpanah, Y (reprint author), Univ Paris Diderot, Hop Bichat Claude Bernard, Serv Malad Infectieuses & Trop, 46 Rue Henri Huchard, F-75877 Paris, France. EM yyazdan@yahoo.com FU Sidaction; Agence National de Recherches sur le SIDA et les hepatitis virales (ANRS); National Institute of Allergy and Infectious Diseases [R37 AI042006, K24 AI062476]; National Institute on Drug Abuse [R01 DA015612]; Bristol-Myers Squibb; Gilead; Merck; Pfizer; Roche; Tibotec; ViiV Healthcare FX Supported by Sidaction; the Agence National de Recherches sur le SIDA et les hepatitis virales (ANRS); the National Institute of Allergy and Infectious Diseases (R37 AI042006, K24 AI062476); and the National Institute on Drug Abuse (R01 DA015612). None of the funders were involved in designing the study, collecting, analyzing or interpreting the data, preparing the article, or deciding to submit it for publication. All authors were independent from the funding sources.; With the exception of Y.Y., none of the authors report any association that might pose a conflict of interest (e. g., pharmaceutical stock ownership, consultancy, advisory board membership, relevant patents, or research funding). Y.Y. has received travel grants, honoraria for presentation at workshops and consultancy honoraria from Bristol-Myers Squibb, Gilead, Merck, Pfizer, Roche, Tibotec, and ViiV Healthcare. NR 58 TC 34 Z9 36 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 2 PY 2012 VL 26 IS 1 BP 45 EP 56 DI 10.1097/QAD.0b013e32834dce6e PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 863BA UT WOS:000298136600006 PM 22008655 ER PT J AU Weiser, SD Tsai, AC Gupta, R Frongillo, EA Kawuma, A Senkungu, J Hunt, PW Emenyonu, NI Mattson, JE Martin, JN Bangsberg, DR AF Weiser, Sheri D. Tsai, Alexander C. Gupta, Reshma Frongillo, Edward A. Kawuma, Annet Senkungu, Jude Hunt, Peter W. Emenyonu, Nneka I. Mattson, Jennifer E. Martin, Jeffrey N. Bangsberg, David R. TI Food insecurity is associated with morbidity and patterns of healthcare utilization among HIV-infected individuals in a resource-poor setting SO AIDS LA English DT Article DE AIDS; food insecurity; healthcare utilization; HIV; morbidity; Uganda ID ANTIRETROVIRAL THERAPY; PATIENT POPULATION; MEDICAL OUTCOMES; SAN-FRANCISCO; HIV/AIDS; SECURITY; HOMELESS; HUNGER; ADULTS; INSUFFICIENCY AB Objective: We undertook a longitudinal study in rural Uganda to understand the association of food insecurity with morbidity and patterns of healthcare utilization among HIV-infected individuals enrolled in an antiretroviral therapy program. Design: Longitudinal cohort study. Methods: Participants were enrolled from the Uganda AIDS Rural Treatment Outcomes cohort, and underwent quarterly structured interviews and blood draws. The primary predictor was food insecurity measured by the validated Household Food Insecurity Access Scale. Primary outcomes included health-related quality of life measured by the validated Medical Outcomes Study-HIV Physical Health Summary (PHS), incident self-reported opportunistic infections, number of hospitalizations, and missed clinic visits. To estimate model parameters, we used the method of generalized estimating equations, adjusting for sociodemographic and clinical variables. Explanatory variables were lagged by 3 months to strengthen causal interpretations. Results: Beginning in May 2007, 458 persons were followed for a median of 2.07 years, and 40% were severely food insecure at baseline. Severe food insecurity was associated with worse PHS, opportunistic infections, and increased hospitalizations (results were similar in concurrent and lagged models). Mild/moderate food insecurity was associated with missed clinic visits in concurrent models, whereas in lagged models, severe food insecurity was associated with reduced odds of missed clinic visits. Conclusion: Based on the negative impact of food insecurity on morbidity and patterns of healthcare utilization among HIV-infected individuals, policies and programs that address food insecurity should be a critical component of HIV treatment programs worldwide. (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Weiser, Sheri D.; Hunt, Peter W.; Mattson, Jennifer E.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94143 USA. [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Gupta, Reshma] Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. [Frongillo, Edward A.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Kawuma, Annet; Senkungu, Jude; Emenyonu, Nneka I.; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Emenyonu, Nneka I.; Bangsberg, David R.] MIT, Ragon Inst MGH, Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Emenyonu, Nneka I.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Weiser, SD (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, POB 0874, San Francisco, CA 94143 USA. EM Sheri.Weiser@ucsf.edu RI Nguyen, Giang/D-9027-2016; OI Tsai, Alexander/0000-0001-6397-7917 FU National Institutes of Health [R01 MH054907, K23 MH079713, MH-79713-03S1, K24 MH087227, P30 AI027793]; Meyer Family Foundation; Robert Wood Johnson Health and Society Scholars Program FX The study was funded by the National Institutes of Health (R01 MH054907, K23 MH079713 and MH-79713-03S1, K24 MH087227, and P30 AI027793) and the Meyer Family Foundation. S. D. W. received additional support from the Burke Family Foundation. A. C. T. received salary support from the Robert Wood Johnson Health and Society Scholars Program. NR 42 TC 61 Z9 61 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 2 PY 2012 VL 26 IS 1 BP 67 EP 75 DI 10.1097/QAD.0b013e32834cad37 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 863BA UT WOS:000298136600008 PM 21904186 ER PT J AU Shapiro, RL Ribaudo, H Powis, K Chen, J Parekh, N AF Shapiro, Roger L. Ribaudo, Heather Powis, Kathleen Chen, Jennifer Parekh, Natasha TI Extended antenatal use of triple antiretroviral therapy for prevention of mother-to-child transmission of HIV-1 correlates with favorable pregnancy outcomes SO AIDS LA English DT Letter ID LOW-BIRTH-WEIGHT; PRETERM DELIVERY; INFECTED WOMEN; PREMATURE DELIVERY; INCREASED RISK; STILLBIRTH C1 [Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Ribaudo, Heather] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Powis, Kathleen] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Powis, Kathleen] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Chen, Jennifer] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Parekh, Natasha] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Shapiro, RL (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. EM rshapiro@bidmc.harvard.edu NR 15 TC 1 Z9 1 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 2 PY 2012 VL 26 IS 1 BP 120 EP 121 DI 10.1097/QAD.0b013e32834db486 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 863BA UT WOS:000298136600016 PM 22126816 ER PT J AU Salat, DH Williams, VJ Leritz, EC Schnyer, DM Rudolph, JL Lipsitz, LA McGlinchey, RE Milberg, WP AF Salat, David H. Williams, Victoria J. Leritz, Elizabeth C. Schnyer, David M. Rudolph, James L. Lipsitz, Lewis A. McGlinchey, Regina E. Milberg, William P. TI Inter-individual variation in blood pressure is associated with regional white matter integrity in generally healthy older adults SO NEUROIMAGE LA English DT Article ID SMALL VESSEL DISEASE; STROKE RISK PROFILE; DIFFUSION TENSOR; COGNITIVE FUNCTION; HYPERINTENSITY VOLUME; EXECUTIVE FUNCTIONS; SPATIAL STATISTICS; CEREBRAL-ISCHEMIA; ELDERLY-PEOPLE; SPIN-ECHO AB Prior studies have documented a range of brain changes that occur as a result of healthy aging as well as neural alterations due to profound dysregulation in vascular health such as extreme hypertension, cerebrovascular disease and stroke. In contrast, little information exists about the more transitionary state between the normal and abnormal physiology that contributes to vascular disease and cognitive decline. Specifically, little information exists with regard to the influence of systemic vascular physiology on brain tissue structure in older individuals with low risk for cerebrovascular disease and with no evidence of cognitive impairment. We examined the association between resting blood pressure and diffusion tensor imaging (DTI) indices of white matter microstructure in 128 healthy older adults (43-87 years) spanning the normotensive to moderate-severe hypertensive range. Mean arterial blood pressure (MABP) was related to diffusion measures in several regions of the brain with greatest associations in the anterior corpus callosum and lateral frontal, precentral, superior frontal, lateral parietal and precuneus white matter. Associations between white matter integrity and blood pressure remained when controlling for age, when controlling for white matter lesions, and when limiting the analyses to only normotensive, pharmacologically controlled and pre-hypertensive individuals. Of the diffusion measures examined, associations were strongest between MABP and radial diffusivity which may indicate that blood pressure has an influence on myelin structure. Associations between MABP and white matter integrity followed spatial patterns resembling those often attributed to the effects of chronological age, suggesting that systemic cerebrovascular health may play a role in neural tissue degeneration classically ascribed to aging. These results demonstrate the importance of the consideration of vascular physiology in studies of cognitive and neural aging, and that this significance extends to even the normotensive and medically controlled population. These data additionally suggest that optimal management of blood pressure may require consideration of the more subtle influence of vascular health on neural health in addition to the primary goal of prevention of a major cerebrovascular event. Published by Elsevier Inc. C1 [Salat, David H.; Williams, Victoria J.; Leritz, Elizabeth C.; McGlinchey, Regina E.; Milberg, William P.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. [Salat, David H.; Williams, Victoria J.; Leritz, Elizabeth C.; Rudolph, James L.; McGlinchey, Regina E.; Milberg, William P.] VA Boston Healthcare Syst, GRECC, Boston, MA USA. [Salat, David H.; Williams, Victoria J.; Leritz, Elizabeth C.] Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Salat, David H.; Leritz, Elizabeth C.; Lipsitz, Lewis A.; McGlinchey, Regina E.; Milberg, William P.] Harvard Univ, Sch Med, Boston, MA USA. [Williams, Victoria J.; Leritz, Elizabeth C.; Rudolph, James L.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. [Schnyer, David M.] Univ Texas Austin, Austin, TX 78712 USA. [Lipsitz, Lewis A.] Beth Israel Deaconess Med Ctr, Gerontol Div, Hebrew Senior Life Inst Aging Res, Boston, MA 02215 USA. RP Salat, DH (reprint author), MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, MGH Dept Radiol, Bldg 149,13th St,Mail Code 149,2301, Charlestown, MA 02129 USA. EM salat@nmr.mgh.harvard.edu RI McGlinchey, Regina/R-1971-2016 FU National Institute of Nursing Research [R01NR010827]; National Institute of Neurologic Disorders and Stroke (ARRA) [K23NS062148, K23NS062148S1]; National Institute on Aging [P60AG08812, K01AG24898]; Medical Research Service VA FX This research was supported by grants from the National Institute of Nursing Research (R01NR010827), National Institute of Neurologic Disorders and Stroke (K23NS062148 and ARRA funds K23NS062148S1), grants from the National Institute on Aging (P60AG08812 and K01AG24898), and by Medical Research Service VA Merit Review Awards to William Milberg and Regina McGlinchey. The authors would like to thank Marge Ahlquist for her assistance with blood pressure collection on all participants and Juli Dolzhenko for assistance in preparation of this manuscript. We also thank Ruopeng Wang, Van J. Wedeen, TrackVis.org, Martinos Center for Biomedical Imaging, Massachusetts General Hospital for the development of TrackVis software used for tractography procedures. NR 57 TC 44 Z9 45 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 JAN 2 PY 2012 VL 59 IS 1 SI SI BP 181 EP 192 DI 10.1016/j.neuroimage.2011.07.033 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 838CX UT WOS:000296265500019 PM 21820060 ER PT J AU Van Dijk, KRA Sabuncu, MR Buckner, RL AF Van Dijk, Koene R. A. Sabuncu, Mert R. Buckner, Randy L. TI The influence of head motion on intrinsic functional connectivity MRI SO NEUROIMAGE LA English DT Article DE Functional MRI; BOLD; Connectome; Resting-state; Movement ID SENSORY STIMULATION; RESPONSE FUNCTION; RESTING BRAIN; DEFAULT-MODE; FMRI; SIGNAL; FLUCTUATIONS; OPTIMIZATION; RESPIRATION; NETWORK AB Functional connectivity MRI (fcMRI) has been widely applied to explore group and individual differences. A confounding factor is head motion. Children move more than adults, older adults more than younger adults, and patients more than controls. Head motion varies considerably among individuals within the same population. Here we explored the influence of head motion on fcMRI estimates. Mean head displacement, maximum head displacement, the number of micro movements (> 0.1 mm), and head rotation were estimated in 1000 healthy, young adult subjects each scanned for two resting-state runs on matched 3T scanners. The majority of fcMRI variation across subjects was not linked to head motion. However, head motion had significant, systematic effects on fcMRI network measures. Head motion was associated with decreased functional coupling in the default and frontoparietal control networks - two networks characterized by coupling among distributed regions of association cortex. Other network measures increased with motion including estimates of local functional coupling and coupling between left and right motor regions - a region pair sometimes used as a control in studies to establish specificity. Comparisons between groups of individuals with subtly different levels of head motion yielded difference maps that could be mistaken for neuronal effects in other contexts. These effects are important to consider when interpreting variation between groups and across individuals. (C) 2011 Elsevier Inc. All rights reserved. C1 [Van Dijk, Koene R. A.; Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Van Dijk, Koene R. A.; Sabuncu, Mert R.; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Sabuncu, Mert R.] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Cambridge, MA USA. RP Buckner, RL (reprint author), Harvard Univ, Dept Psychol, Ctr Brain Sci, 52 Oxford St,Northwest Bldg 280-06, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu RI Van Dijk, Koene/G-3317-2012 OI Van Dijk, Koene/0000-0001-6137-4282 FU NIA [AG021910, P41RR14074, K08MH067966]; Howard Hughes Medical Institute; Simons Foundation; KL2 Medical Research Investigator Training (MeRIT) grant awarded via Harvard Catalyst; Harvard Clinical and Translational Science Center (NIH) [1KL2RR025757]; Harvard University FX We thank the Harvard Center for Brain Science Neuroimaging Core, the Athinoula A. Martinos Center for imaging support, and the Harvard Neuroinformatics Research Group (Gabriele Fariello, Timothy O'Keefe, and Victor Petrov). The data analyzed were collected as part of the Genomics Superstruct Project. We thank Marisa Hollinshead, Elizabeth Hemphill, Leah Bakst, Angela Castellanos, and Sara Rubenstein for assistance in collecting the data. Avram Holmes and Jorge Sepulcre assisted in constructing the functional connectivity measures, and Avi Snyder provided valuable discussion. This work was supported by NIA Grants (AG021910, P41RR14074, K08MH067966), the Howard Hughes Medical Institute, and the Simons Foundation. Dr. Sabuncu receives support from a KL2 Medical Research Investigator Training (MeRIT) grant awarded via Harvard Catalyst, The Harvard Clinical and Translational Science Center (NIH grant 1KL2RR025757 and financial contributions from Harvard University and its affiliated academic health care centers). NR 44 TC 763 Z9 765 U1 7 U2 74 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 JAN 2 PY 2012 VL 59 IS 1 SI SI BP 431 EP 438 DI 10.1016/j.neuroimage.2011.07.044 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 838CX UT WOS:000296265500043 PM 21810475 ER PT J AU Foland-Ross, LC Bookheimer, SY Lieberman, MD Sugar, CA Townsend, JD Fischer, J Torrisi, S Penfold, C Madsen, SK Thompson, PM Altshuler, LL AF Foland-Ross, Lara C. Bookheimer, Susan Y. Lieberman, Matthew D. Sugar, Catherine A. Townsend, Jennifer D. Fischer, Jeffrey Torrisi, Salvatore Penfold, Conor Madsen, Sarah K. Thompson, Paul M. Altshuler, Lori L. TI Normal amygdala activation but deficient ventrolateral prefrontal activation in adults with bipolar disorder during euthymia SO NEUROIMAGE LA English DT Article DE Bipolar disorder; Amygdala; Prefrontal cortex; fMRI; Emotion ID MOTOR RESPONSE-INHIBITION; ORBITOFRONTAL CORTEX; AFFECTIVE STIMULI; BRAIN ACTIVATION; RATING-SCALE; MANIA; FMRI; TASK; ABNORMALITIES; OPTIMIZATION AB Functional neuroimaging studies have implicated the involvement of the amygdala and ventrolateral prefrontal cortex (vIPFC) in the pathophysiology of bipolar disorder. Hyperactivity in the amygdala and hypoactivity in the vIPFC have been reported in manic bipolar patients scanned during the performance of an affective faces task. Whether this pattern of dysfunction persists during euthymia is unclear. Using functional magnetic resonance imaging (fMRI), 24 euthymic bipolar and 26 demographically matched healthy control subjects were scanned while performing an affective task paradigm involving the matching and labeling of emotional facial expressions. Neuroimaging results showed that, while amygdala activation did not differ significantly between groups, euthymic patients showed a significant decrease in activation of the right vIPFC (BA47) compared to healthy controls during emotion labeling. Additionally, significant decreases in activation of the right insula, putamen, thalamus and lingual gyrus were observed in euthymic bipolar relative to healthy control subjects during the emotion labeling condition. These data, taken in context with prior studies of bipolar mania using the same emotion recognition task, could suggest that amygdala dysfunction may be a state-related abnormality in bipolar disorder, whereas vIPFC dysfunction may represent a trait-related abnormality of the illness. Characterizing these patterns of activation is likely to help in understanding the neural changes related to the different mood states in bipolar disorder, as well as changes that represent more sustained abnormalities. Future studies that assess mood-state related changes in brain activation in longitudinal bipolar samples would be of interest. Published by Elsevier Inc. C1 [Altshuler, Lori L.] Univ Calif Los Angeles, Mood Disorders Res Program, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Foland-Ross, Lara C.; Madsen, Sarah K.; Thompson, Paul M.] Univ Calif Los Angeles, Lab NeuroImaging, Dept Neurol, Sch Med, Los Angeles, CA 90095 USA. [Lieberman, Matthew D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Altshuler, Lori L.] W Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, Mood Disorders Res Program, Dept Psychiat & Biobehav Sci, 300 Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU National Institute of Mental Health [MH078556, MH075944, MH01848]; National Institute on Aging (NIA); National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Center for Research Resources (NCRR) [AG016570, EB01651, RR019771, RR12169, RR13642, RR00865] FX This work was supported by grants from the National Institute of Mental Health (MH078556 to LCFR, and MH075944 and MH01848 to LLA). Additional support for algorithm development was provided by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), and the National Center for Research Resources (NCRR; AG016570, EB01651, RR019771 to PT). For their generous support, the authors also thank the National Association for Research on Schizophrenia and Affective Disorders (NARSAD), Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, The Ahmanson Foundation, William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family and Northstar Fund. The project was also supported by grant numbers RR12169, RR13642 and RR00865 from the NCRR. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. NR 42 TC 38 Z9 40 U1 2 U2 7 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 JAN 2 PY 2012 VL 59 IS 1 SI SI BP 738 EP 744 DI 10.1016/j.neuroimage.2011.07.054 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 838CX UT WOS:000296265500073 PM 21854858 ER PT S AU Faber, AC Ebi, H Costa, C Engelman, JA AF Faber, Anthony C. Ebi, Hiromichi Costa, Carlotta Engelman, Jeffrey A. BE Smalley, KSM TI Apoptosis In Targeted Therapy Responses: The Role of BIM SO CURRENT CHALLENGES IN PERSONALIZED CANCER MEDICINE SE Advances in Pharmacology LA English DT Article; Book Chapter ID CELL LUNG-CANCER; GROWTH-FACTOR-RECEPTOR; TYROSINE KINASE INHIBITORS; CHRONIC MYELOGENOUS LEUKEMIA; ABL-POSITIVE CELLS; ACQUIRED-RESISTANCE; BCR-ABL; BREAST-CANCER; HOMOZYGOUS DELETIONS; GENE AMPLIFICATION AB The treatment of advanced cancer has undergone a dramatic change over the past 5 years. Laboratory findings have led to the development of newer treatments, often termed "targeted therapies," which are significantly different from traditional chemotherapies in that they aim to disrupt critical processes needed specifically for a cancer cell's growth and survival, therefore, eliminating some of the general toxicities of chemotherapies. Cancers with specific genetic abnormalities, for instance epidermal growth factor receptor (EGFR) mutant lung cancers and HER2 amplified breast cancers, are often sensitive to these new targeted therapies that can specifically inhibit the function of EGFR or HER2. This has led to more routine prospective genetic testing of cancers to determine which patients should get these treatments instead of chemotherapy. However, emerging clinical data have revealed that some cancers with these genetic mutations (that predict a response) are unexpectedly not sensitive to these treatments. There is a growing body of evidence suggesting a deficiency in apoptosis following targeted therapy treatment can lead to this lack of sensitivity. Moreover, the pro-apoptotic protein BIM has emerged as a key modulator of apoptosis following effective targeted therapy, and deficiencies in BIM expression result in targeted therapy resistance. In this chapter, we summarize what is known about the role of BIM in targeted therapy-induced apoptosis, and discuss the implications of deficient BIM in cancers treated with these therapies. We highlight potential pharmaceutical strategies to overcome low BIM expression and sensitize these cancers to targeted therapies. C1 [Faber, Anthony C.; Ebi, Hiromichi; Costa, Carlotta; Engelman, Jeffrey A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr, Boston, MA 02129 USA. RP Faber, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Canc Ctr, Boston, MA 02129 USA. OI Ebi, Hiromichi/0000-0003-3155-7576 FU NCI NIH HHS [P50 CA090578, P50 CA127003, P50CA090578, R01CA135257-01, R01CA137008-01, R01CA140594, R01CA164273] NR 88 TC 30 Z9 30 U1 0 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1054-3589 BN 978-0-12-398483-8; 978-0-12-397927-8 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2012 VL 65 BP 519 EP 542 DI 10.1016/B978-0-12-397927-8.00016-6 PG 24 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BIE72 UT WOS:000327897900017 PM 22959036 ER PT S AU Dutta, J El Fakhri, G Lin, YG Huang, C Petibon, Y Reese, TG Leahy, RM Li, QZ AF Dutta, Joyita El Fakhri, Georges Lin, Yanguang Huang, Chuan Petibon, Yoann Reese, Timothy G. Leahy, Richard M. Li, Quanzheng BE Yu, B TI Spatially Varying Regularization for Motion Compensated PET Reconstruction SO 2012 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE RECORD (NSS/MIC) SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop CY OCT 29-NOV 03, 2012 CL Anaheim, CA SP IEEE, IEEE Nucl & Plasma Sci Soc ID LIKELIHOOD IMAGE-RECONSTRUCTION; RESOLUTION PROPERTIES; MRI AB Motion-compensated PET reconstruction enables reduction of blurring artifacts in PET images caused by respiratory or cardiac motion without sacrificing signal-to-noise ratio. The motion-compensated image reconstruction problem can be solved using a maximum a posteriori ( MAP) reconstruction scheme. It is well known that for the uniform quadratic penalty, MAP generates images with a spatially varying resolution. We present here a regularization approach to mitigate this effect by spatially adjusting the degree of smoothing in an automated fashion in the motion-compensated MAP reconstruction framework. Our method is based on an analytical approximation for the diagonal elements of the Fisher information matrix which can be used to control the local impulse response at each voxel. We have applied the developed regularization scheme to respiratory gated studies on the NCAT torso phantom with simulated lung lesions. We compared our regularization scheme for multi-gate reconstruction with the uniform quadratic penalty, ungated reconstruction, and single-gate reconstruction. We show that for multi-gate reconstruction, both activity and motion influence the variance for each voxel of the reconstructed image. Accordingly our regularizer yields higher gains in contrast recovery relative to the UQP in lesions that move substantially during breathing. C1 [Dutta, Joyita; El Fakhri, Georges; Huang, Chuan; Petibon, Yoann; Li, Quanzheng] Massachusetts Gen Hosp, Ctr Adv Radiol Sci, Boston, MA 02114 USA. [Lin, Yanguang; Leahy, Richard M.] Univ Southern Calif, Dept Elect Engn, Los Angeles, CA 90089 USA. RP Dutta, J (reprint author), Massachusetts Gen Hosp, Ctr Adv Radiol Sci, Boston, MA 02114 USA. EM Dutta.Joyita@mgh.harvard.edu; elfakhri@pet.mgh.harvard.edu; yanguanl@usc.edu; huang@pet.mgh.harvard.edu; petibon@pet.mgh.harvard.edu; reese@nmr.mgh.harvard.edu; leahy@sipi.usc.edu; Li.Quanzheng@mgh.harvard.edu FU NIH [R21EB012326, R01CA165221] FX This work was funded in part by NIH R21EB012326 and R01CA165221. NR 12 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4673-2030-6; 978-1-4673-2028-3 J9 IEEE NUCL SCI CONF R PY 2012 BP 2156 EP 2160 PG 5 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BHW16 UT WOS:000326814202053 ER PT S AU Grogg, K Zhu, X Min, CH Winey, B Bortfeld, T Paganetti, H Shih, H El Fakhri, G AF Grogg, K. Zhu, X. Min, C. H. Winey, B. Bortfeld, T. Paganetti, H. Shih, H. El Fakhri, G. BE Yu, B TI Feasibility of using distal endpoints for In-room PET Range Verification of Proton Therapy SO 2012 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE RECORD (NSS/MIC) SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop CY OCT 29-NOV 03, 2012 CL Anaheim, CA SP IEEE, IEEE Nucl & Plasma Sci Soc ID MONTE-CARLO SIMULATIONS; BEAMS AB In an effort to verify the dose delivery in proton therapy, Positron Emission Tomography (PET) scans have been employed to measure the distribution of beta+ radioactivity produced from nuclear reactions of the protons with native nuclei. Because the dose and PET distributions are not directly comparable, the range verification is currently carried out by comparing measured and Monte Carlo (MC) simulation predicted PET distributions. In order to reduce the reliance on MC, MC-PET and dose distal endpoints were compared to explore the feasibility of using distal endpoints for in-room PET range verification. MC simulations were generated for six head and neck patients with corrections for radiological decay, biological washout, and PET resolution. One-dimensional profiles of the dose and MC-PET were examined along the direction of the beam and covering the cross section of the beam. The chosen endpoints of the MC-PET (y-intercept of the linear fit to the distal falloff) and MC dose (20-50% of maximum dose) correspond to where most of the protons are below the threshold energy for the nuclear reactions. The difference in endpoint range between the distal surfaces of the dose and MC-PET are compared and the spread of range differences are assessed. Among the six patients, the mean difference between MC-PET and dose depth was found to be -1.5 mm to +3.7 mm between patients, with a standard deviation of 1.3 to 6 mm across the individual beams. C1 [Grogg, K.; Zhu, X.; El Fakhri, G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Grogg, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4673-2030-6; 978-1-4673-2028-3 J9 IEEE NUCL SCI CONF R PY 2012 BP 3890 EP 3894 PG 5 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BHW16 UT WOS:000326814203229 ER PT S AU Koybasi, O Childres, I Jovanovic, I Chen, Y AF Koybasi, Ozhan Childres, Isaac Jovanovic, Igor Chen, Yong BE Yu, B TI Design and Simulation of a Graphene DEPFET Detector SO 2012 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE RECORD (NSS/MIC) SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop CY OCT 29-NOV 03, 2012 CL Anaheim, CA SP IEEE, IEEE Nucl & Plasma Sci Soc AB Graphene field effect transistors (GFETs) fabricated on undoped semiconductor substrates have shown promise for sensing ionizing radiation with a potential of high sensitivity, low noise, low power, and room temperature operation. Radiation detection with GFET is based on the high sensitivity of graphene resistivity on local electric field perturbations caused by ionized charges generated in an electrically biased radiation absorbing semiconductor substrate. Those charges are drifted to the neighborhood of graphene by the gate voltage applied across the detector. GFET radiation sensors can be fabricated on a variety of substrates, exploiting their distinct material properties, to address different application regimes. The current simple GFETs lack the functionality of efficiently removing ionized charges accumulated underneath graphene after signal readout, which results in a slow response to irradiation cut-off and therefore compromises the ability to operate in the pulse mode. In order to overcome this limitation, we propose here a more advanced device architecture, namely, graphene DEPFET. C1 [Koybasi, Ozhan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Childres, Isaac] Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA. [Jovanovic, Igor] Penn State Univ, Dept Mech & Nucl Engn, University Pk, PA 16802 USA. [Chen, Yong] Purdue Univ, Birck Nanotechnol Ctr, Dept Elect & Comp Engn, W Lafayette, IN 47907 USA. RP Koybasi, O (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM okoybasi@partners.org; ichildre@purdue.edu; ijovanovic@psu.edu; yongchen@purdue.edu FU Department of Homeland Security and Department of Defense [2009-DN-077- AR 1036- 02, HDTRA 1-09-1-0047] FX This work has been supported by Department of Homeland Security and Department of Defense under awards 2009-DN-077- AR 1036- 02 and HDTRA 1-09-1-0047, respectively. NR 13 TC 2 Z9 2 U1 0 U2 5 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4673-2030-6; 978-1-4673-2028-3 J9 IEEE NUCL SCI CONF R PY 2012 BP 4249 EP 4254 PG 6 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BHW16 UT WOS:000326814204073 ER PT S AU Koybasi, O Goulet, M Depauw, N Gingras, L Archambault, L Beaulieu, L Seco, J AF Koybasi, Ozhan Goulet, Mathieu Depauw, Nick Gingras, Luc Archambault, Louis Beaulieu, Luc Seco, Joao BE Yu, B TI Development of a 2D Scintillating Fiber Detector for Proton Radiography SO 2012 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE RECORD (NSS/MIC) SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium / Medical Imaging Conference Record (NSS/MIC) / 19th Room-Temperature Semiconductor X-ray and Gamma-ray Detector Workshop CY OCT 29-NOV 03, 2012 CL Anaheim, CA SP IEEE, IEEE Nucl & Plasma Sci Soc AB Proton therapy offers the advantages of a superior target dose conformality and lower integral dose over the conventional photon therapy. However, range uncertainties associated with dose calculation approximations, tumor motion, setup variations, etc., present a major concern in proton therapy. In order to address this issue, we are developing a 2 mm resolution scintillating fiber detector with fibers arranged such that they form a 2D matrix that allows the determination of x- and y-position of the proton. By implementing a scheme consisting only of one detector positioned in front of the patient and another detector behind the patient, we can potentially realize a real-time measurement of proton position, direction, and range/energy simultaneously to reconstruct proton radiographs, also eliminating the need to use an additional bulky range telescope or calorimeter which is not appropriate for in vivo clinical use. C1 [Koybasi, Ozhan; Depauw, Nick; Seco, Joao] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goulet, Mathieu; Gingras, Luc; Archambault, Louis; Beaulieu, Luc] Hotel Dieu Quebec, Dept Radio Oncol, Quebec City, PQ GIR 2J6, Canada. [Goulet, Mathieu; Gingras, Luc; Archambault, Louis; Beaulieu, Luc] Hotel Dieu Quebec, ctr Rech Cancerol, Quebec City, PQ GIR 2J6, Canada. [Goulet, Mathieu; Gingras, Luc; Archambault, Louis; Beaulieu, Luc] Univ Laval, Dept Phys Genie Phys & Opt, Quebec City, PQ G1V 0A6, Canada. [Depauw, Nick] Univ Wollongong, Wollongong, NSW 2522, Australia. RP Koybasi, O (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM okoybasi@partners.org; mathieu.goulet.5@ulaval.ca; ndepauw@partners.org; beaulieu@phy.ulaval.ca; jseco@partners.org RI Beaulieu, Luc/A-6803-2009 OI Beaulieu, Luc/0000-0003-0429-6366 FU National Cancer Institute [POICA021239] FX This work has been supported by National Cancer Institute under award POICA021239. NR 8 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4673-2030-6; 978-1-4673-2028-3 J9 IEEE NUCL SCI CONF R PY 2012 BP 4318 EP 4323 PG 6 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BHW16 UT WOS:000326814204088 ER PT J AU Lim, JL Hu, DJJ Cui, DY Yoo, S Shum, PP Loh, W AF Lim, Jun Long Hu, Dora Juan Juan Cui, Dongyao Yoo, Seongwoo Shum, Perry Ping Loh, Wei GP IEEE TI Characteristics of Suspended-Core Fiber Interferometer: Modal Analysis SO 2012 PHOTONICS GLOBAL CONFERENCE (PGC) LA English DT Proceedings Paper CT Photonics Global Conference (PGC) CY DEC 13-16, 2012 CL Singapore, SINGAPORE DE Photonic crystal fiber; interferometer; suspended-core; interference ID PHOTONIC CRYSTAL FIBER AB Suspended-core fiber (SCF) represents a promising class of microstructured optical fibers for sensing applications. In this work, we present a thorough modal analysis of the SCF based modal interferometer which is constructed by splicing 50 mm of SCF to single mode fiber at both ends. The measured transmission spectrum exhibits three-beam interference-like spectrum. In the modal analysis, we investigate the intermodal coupling between the fundamental and higher-order modes, as well as the coupling between the orthogonal polarizations in the fundamental modes. In comparison with the typical two-mode interferences in photonic crystal fiber interferometers, the measured spectrum of SCF interferometer has distinctively sharper spectrum for high resolution and high dynamic range application. C1 [Lim, Jun Long; Hu, Dora Juan Juan] ASTAR, RF, Antenna & Opt Dept, Inst Infocomm Res, Singapore, Singapore. RP Hu, DJJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jjhu@i2r.a-star.edu.sg RI LIM, Jun Long/D-5658-2011; HU, Dora Juan Juan/J-2995-2016 OI HU, Dora Juan Juan/0000-0001-8822-3900 NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-2516-5 PY 2012 PG 3 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BHE75 UT WOS:000325203600100 ER PT J AU Lim, JL Hu, DJJ Shum, PP Wang, YX Hao, EJ AF Lim, Jun Long Hu, Dora Juan Juan Shum, Perry Ping Wang, Yixin Hao, Emily Jianzhong GP IEEE TI Microbubble-Enabled Photonic Crystal Fiber-based Sensors SO 2012 PHOTONICS GLOBAL CONFERENCE (PGC) LA English DT Proceedings Paper CT Photonics Global Conference (PGC) CY DEC 13-16, 2012 CL Singapore, SINGAPORE DE Photonic crystal fiber; interferometer; microbubble; temperature; strain; refractive index; sensing AB A review of photonic crystal fiber sensors with microbubble is presented. The work concentrate in three sensing fields: the first reports on temperature sensing; the second describes on strain sensing; the last part focuses on refractive index sensing and bio-sensing. The method of fabricating the microbubble is also briefly discussed. C1 [Hu, Dora Juan Juan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hu, DJJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jjhu@i2r.a-star.edu.sg RI LIM, Jun Long/D-5658-2011; HU, Dora Juan Juan/J-2995-2016 OI HU, Dora Juan Juan/0000-0001-8822-3900 NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-2516-5 PY 2012 PG 2 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BHE75 UT WOS:000325203600028 ER PT J AU Shacka, JJ AF Shacka, John J. BE Yue, Z Chu, CT TI LYSOSOME STORAGE DISORDERS ON THE BRAIN: THE AUTOPHAGY LYSOSOME PATHWAY CONTRIBUTES TO DISEASE PATHOPHYSIOLOGY AND MAY BE UTILIZED FOR THERAPEUTIC BENEFIT SO AUTOPHAGY OF THE NERVOUS SYSTEM: CELLULAR SELF-DIGESTION IN NEURONS AND NEUROLOGICAL DISEASES LA English DT Article; Book Chapter ID MUCOLIPIDOSIS TYPE-IV; NEURONAL CEROID-LIPOFUSCINOSES; CATHEPSIN-D DEFICIENCY; NEURONOPATHIC GAUCHER-DISEASE; CHAPERONE-MEDIATED AUTOPHAGY; SAPOSIN C DEFICIENCY; NIEMANN-PICK-DISEASE; CELL-DEATH PATHWAYS; POMPE-DISEASE; BATTEN-DISEASE AB Lysosome storage disorders (LSDs) are defined by genetic mutations that either directly or indirectly compromise lysosome function, many of which exhibit documented CNS pathophysiology. As lysosome dysfunction is a principal contributing factor to the onset and progression of LSDs, it is not surprising to learn of several reports documenting inherent abnormalities in the autophagy-lysosome pathway (ALP), as the ALP requires itntact lysosome function for its proper clearance of substrates and homeostatic maintenance of energy balance. In addition, accumulating evidence suggests that alterations in ALP signaling contribute to the onset and progression of adult onset neurodegenerative disease. Thus the study of LSD mutations and their effects on the ALP has aided in our understanding of ALP-associated contributions to diseases such as Alzheimer's and Parkinson's. Herein we will review LSDs with known CNS pathophysiology and will discuss the often heterogeneous ALP abnormalities amongst these diseases. LSD-specific therapies will also be discussed and how the ALP may be a direct or indirect target of such therapies. Finally, the function of the ALP in LSDs will be discussed relative to its putative role in adult onset neurodegenerative disease. C1 [Shacka, John J.] Univ Alabama Birmingham, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. [Shacka, John J.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. RP Shacka, JJ (reprint author), Univ Alabama Birmingham, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. EM shacka@uab.edu RI di Ronza, Alberto/H-7674-2016 OI di Ronza, Alberto/0000-0002-9813-5143 NR 82 TC 0 Z9 0 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4350-44-0 PY 2012 BP 331 EP 354 D2 10.1142/8150 PG 24 WC Neurosciences SC Neurosciences & Neurology GA BHZ39 UT WOS:000327076800015 ER PT B AU Pereyra, F Walker, BD AF Pereyra, Florencia Walker, Bruce D. BE Pancino, G Silvestri, G Fowke, KR TI Immune Responses Associated to Viral Control SO MODELS OF PROTECTION AGAINST HIV/SIV: AVOIDING AIDS IN HUMANS AND MONKEYS LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; HLA-B-ASTERISK-57(+) ELITE SUPPRESSORS; NEUTRALIZING ANTIBODY-RESPONSES; LONG-TERM NONPROGRESSORS; UNTREATED HIV-INFECTION; CTL ESCAPE MUTATIONS; NATURAL-KILLER-CELLS; LOW-LEVEL VIREMIA; TYPE-1 INFECTION C1 [Pereyra, Florencia; Walker, Bruce D.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA 02129 USA. RP Pereyra, F (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, East Campus, Charlestown, MA 02129 USA. NR 104 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-387716-1; 978-0-12-387715-4 PY 2012 BP 273 EP 291 DI 10.1016/B978-0-12-387715-4.00010-1 PG 19 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA BHU09 UT WOS:000326658900011 ER PT J AU Erickson, CA Peay, KI McDougle, CJ AF Erickson, Craig A. Peay, Khendra I. McDougle, Christopher J. BE Nurnberger, JI Berrettini, WH TI Developmental disorders SO PRINCIPLES OF PSYCHIATRIC GENETICS LA English DT Article; Book Chapter ID SMITH-MAGENIS-SYNDROME; FRAGILE-X-SYNDROME; PRADER-WILLI-SYNDROME; ANGELMAN-SYNDROME; RETT-SYNDROME; MENTAL-RETARDATION; DOWN-SYNDROME; BEHAVIORAL-PHENOTYPE; MALADAPTIVE BEHAVIOR; SYNAPTIC PLASTICITY C1 [Erickson, Craig A.; Peay, Khendra I.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Erickson, Craig A.; Peay, Khendra I.] James Whitcomb Riley Hosp Children, Christian Sarkine Autism Treatment Ctr, Indianapolis, IN 46202 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Boston, MA 02114 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA. RP Erickson, CA (reprint author), Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. NR 60 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-89649-8 PY 2012 BP 363 EP 370 D2 10.1017/CBO9781139025997 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA BHV51 UT WOS:000326744300031 ER PT B AU Harrington, D AF Harrington, David BE Harrington, D TI Designs for Clinical Trials Perspectives on Current Issues Preface SO DESIGNS FOR CLINICAL TRIALS: PERSPECTIVES ON CURRENT ISSUES SE Applied Bioinformatics and Biostatistics in Cancer Research LA English DT Editorial Material; Book Chapter C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Harrington, D (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM david_harrington@dfci.harvard.edu NR 1 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-0140-7; 978-1-4614-0139-1 J9 APPL BIOINF BIOSTAT JI Appl. Bioinf. Biostat. Canc. Res. PY 2012 BP VII EP IX D2 10.1007/978-1-4614-0140-7 PG 3 WC Oncology; Mathematical & Computational Biology SC Oncology; Mathematical & Computational Biology GA BHN08 UT WOS:000325951800001 ER PT B AU Miller, JD Seyedali, M Hahn, ME AF Miller, Jason D. Seyedali, Mahyo Hahn, Michael E. GP ASME TI WALKING MODE CLASSIFICATION FROM MYOELECTRIC AND INERTIAL FUSION SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE, PTS A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference (SBC) CY JUN 20-23, 2012 CL Fajardo, PR C1 [Miller, Jason D.; Seyedali, Mahyo; Hahn, Michael E.] VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence, Seattle, WA 98108 USA. RP Miller, JD (reprint author), VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence, Seattle, WA 98108 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4480-9 PY 2012 BP 797 EP 798 PG 2 WC Engineering, Biomedical; Engineering, Mechanical SC Engineering GA BHD11 UT WOS:000325036600398 ER PT B AU Peterson, TJ Roland, M Adamczyk, P Hahn, ME AF Peterson, Travis J. Roland, Michelle Adamczyk, Peter Hahn, Michael E. GP ASME TI THE EFFECT OF PROSTHETIC FOOT COMPONENT STIFFNESS ON GAIT INITIATION AND TERMINATION OF TRANSTIBIAL AMPUTEES SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE, PTS A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference (SBC) CY JUN 20-23, 2012 CL Fajardo, PR ID LOWER-LIMB AMPUTEES C1 [Peterson, Travis J.; Roland, Michelle; Hahn, Michael E.] VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence, Seattle, WA 98105 USA. RP Peterson, TJ (reprint author), VA Puget Sound Hlth Care Syst, RR&D Ctr Excellence, Seattle, WA 98105 USA. RI Adamczyk, Peter/P-5928-2014 OI Adamczyk, Peter/0000-0001-5374-7691 NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4480-9 PY 2012 BP 803 EP 804 PG 2 WC Engineering, Biomedical; Engineering, Mechanical SC Engineering GA BHD11 UT WOS:000325036600401 ER PT B AU Wang, S Park, WM Miao, J Wood, K Kim, YH Li, G AF Wang, S. Park, W. M. Miao, J. Wood, K. Kim, Y. H. Li, G. GP ASME TI IN-VIVO LOADS ON THE LUMBAR INTERVERTEBRAL DISCS DURING WEIGHT LIFTING SO PROCEEDINGS OF THE ASME SUMMER BIOENGINEERING CONFERENCE, PTS A AND B LA English DT Proceedings Paper CT ASME Summer Bioengineering Conference (SBC) CY JUN 20-23, 2012 CL Fajardo, PR ID VALIDATION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wang, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MECHANICAL ENGINEERS PI NEW YORK PA THREE PARK AVENUE, NEW YORK, NY 10016-5990 USA BN 978-0-7918-4480-9 PY 2012 BP 1079 EP 1080 PG 2 WC Engineering, Biomedical; Engineering, Mechanical SC Engineering GA BHD11 UT WOS:000325036600539 ER PT J AU Chavarro, JE Colaci, DS Afeiche, M Gaskins, AJ Wright, D Toth, TL Hauser, R AF Chavarro, J. E. Colaci, D. S. Afeiche, M. Gaskins, A. J. Wright, D. Toth, T. L. Hauser, R. TI Dietary fat intake and in-vitro fertilization outcomes: saturated fat intake is associated with fewer metaphase 2 oocytes SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 28th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE) CY JUL 01-04, 2012 CL Istanbul, TURKEY SP European Soc Human Reprod & Embryol C1 [Chavarro, J. E.; Colaci, D. S.; Afeiche, M.; Gaskins, A. J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Wright, D.; Toth, T. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hauser, R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. 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 0268-1161 J9 HUM REPROD JI Hum. Reprod. PY 2012 VL 27 SU 2 MA O-200 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 229WW UT WOS:000325299600196 ER PT J AU Iager, AE Kocabas, AM Otu, HH Ruppel, P Langerveld, A Schnarr, P Suarez, M Jarrett, JC Conaghan, J Rosa, GJM Fernandez, E Rawlins, RG Cibelli, JB Crosby, J AF Iager, A. E. Kocabas, A. M. Otu, H. H. Ruppel, P. Langerveld, A. Schnarr, P. Suarez, M. Jarrett, J. C. Conaghan, J. Rosa, G. J. M. Fernandez, E. Rawlins, R. G. Cibelli, J. B. Crosby, J. TI A novel biomarker signature expressed in human cumulus cells predicts oocyte pregnancy potential during ART SO HUMAN REPRODUCTION LA English DT Meeting Abstract CT 28th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE) CY JUL 01-04, 2012 CL Istanbul, TURKEY SP European Soc Human Reprod & Embryol C1 [Iager, A. E.] Gema Diagnost Inc, Ann Arbor, MI USA. [Kocabas, A. M.] Rockefeller Univ, Lab Dev Neurobiol, New York, NY 10021 USA. [Otu, H. H.] Dana Farber Harvard Canc Ctr, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Ruppel, P.] Innovat Analyt, Kalamazoo, MI USA. [Langerveld, A.] GeneMarkers, Kalamazoo, MI USA. [Schnarr, P.; Jarrett, J. C.] Jarrett Fertil Grp, Carmel, IN USA. [Suarez, M.] Stanford Hosp, Stanford Fertil & Reprod Med Ctr, Palo Alto, CA USA. [Conaghan, J.] Pacific Fertil Ctr, IVF Lab, San Francisco, CA USA. [Rosa, G. J. M.] Univ Wisconsin, Dept Anim Sci, Madison, WI USA. [Rosa, G. J. M.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Fernandez, E.; Crosby, J.] Clin Las Condes, Unidad Med Reprod, Santiago, Chile. [Rawlins, R. G.] Rush Univ, Med Ctr, Dept Obstet & Gynecol, Chicago, IL 60612 USA. [Cibelli, J. B.] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA. [Cibelli, J. B.] Michigan State Univ, Dept Anim Sci, E Lansing, MI 48824 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 0268-1161 J9 HUM REPROD JI Hum. Reprod. PY 2012 VL 27 SU 2 MA O-004 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 229WW UT WOS:000325299600005 ER PT J AU Balu, DT Goff, DC AF Balu, Darrick T. Goff, Donald C. BE Barrett, JE Coyle, JT Williams, M TI Schizophrenia SO TRANSLATIONAL NEUROSCIENCE: APPLICATIONS IN PSYCHIATRY, NEUROLOGY, AND NEURODEVELOPMENTAL DISORDERS LA English DT Article; Book Chapter ID NEUROTROPHIC FACTOR VAL66MET; PLACEBO-CONTROLLED TRIAL; DENDRITIC SPINE DENSITY; TREATMENT-RESISTANT SCHIZOPHRENIA; MAGNETIC-RESONANCE SPECTROSCOPY; RECEPTOR AGONIST XANOMELINE; CORTICAL PYRAMIDAL NEURONS; CONTROLLED CROSSOVER TRIAL; NEUREGULIN-1 NRG1 GENE; CENTRAL-NERVOUS-SYSTEM C1 [Balu, Darrick T.] Harvard Univ, Sch Med, Belmont, MA 02178 USA. [Goff, Donald C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Balu, DT (reprint author), Harvard Univ, Sch Med, Belmont, MA 02178 USA. NR 277 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-51976-2 PY 2012 BP 80 EP 106 D2 10.1017/CBO9780511980053 PG 27 WC Neurosciences SC Neurosciences & Neurology GA BHB34 UT WOS:000324875800005 ER PT J AU Sandrock, AW Rudick, RA AF Sandrock, Alfred W., Jr. Rudick, Richard A. BE Barrett, JE Coyle, JT Williams, M TI Multiple sclerosis SO TRANSLATIONAL NEUROSCIENCE: APPLICATIONS IN PSYCHIATRY, NEUROLOGY, AND NEURODEVELOPMENTAL DISORDERS LA English DT Article; Book Chapter ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; PLACEBO-CONTROLLED MULTICENTER; RESONANCE-IMAGING LESIONS; STEM-CELL TRANSPLANTATION; MS FUNCTIONAL COMPOSITE; APPEARING WHITE-MATTER; T-REGULATORY-CELLS; EPSTEIN-BARR-VIRUS; QUALITY-OF-LIFE C1 [Sandrock, Alfred W., Jr.] Biogen Idec Inc, Neurol Res & Dev, Cambridge, MA USA. [Sandrock, Alfred W., Jr.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rudick, Richard A.] Cleveland Clin, Mellen Ctr Multiple Sclerosis Treatment & Res, Neurol Inst, Cleveland, OH 44106 USA. RP Sandrock, AW (reprint author), Biogen Idec Inc, Neurol Res & Dev, Cambridge, MA USA. NR 124 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-51976-2 PY 2012 BP 178 EP 196 D2 10.1017/CBO9780511980053 PG 19 WC Neurosciences SC Neurosciences & Neurology GA BHB34 UT WOS:000324875800011 ER PT B AU Kuhlthau, K AF Kuhlthau, Karen BE Talley, RC Crews, JE TI Parent Caregivers of Children with Disabilities SO MULTIPLE DIMENSIONS OF CAREGIVING AND DISABILITY: RESEARCH, PRACTICE, POLICY SE Caregiving-Research Practice Policy LA English DT Article; Book Chapter ID PEDIATRIC HOME CARE; SEVERE PHYSICAL-DISABILITY; HEALTH-CARE; CHRONIC ILLNESS; DISABLED-CHILDREN; PSYCHOLOGICAL DISTRESS; CHILDHOOD DISABILITY; SUPPORT INTERVENTION; SOCIAL SUPPORT; MENTAL-HEALTH C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. RP Kuhlthau, K (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM kkuhlthau@partners.org NR 79 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-3383-5 J9 CAREGIVING-RES PRACT PY 2012 BP 67 EP 82 DI 10.1007/978-1-4614-3384-2_5 D2 10.1007/978-1-4614-3384-2 PG 16 WC Health Policy & Services; Social Work SC Health Care Sciences & Services; Social Work GA BGN70 UT WOS:000323583000006 ER PT J AU Amick, MM Miller, IN Neargarder, S Cronin-Golomb, A AF Amick, Melissa M. Miller, Ivy N. Neargarder, Sandy Cronin-Golomb, Alice TI Web-Based Assessment of Visual and Visuospatial Symptoms in Parkinson's Disease SO PARKINSONS DISEASE LA English DT Article ID CONTRAST SENSITIVITY; QUESTIONNAIRE; DYSFUNCTION; PERCEPTION; DRIVERS AB Visual and visuospatial dysfunction is prevalent in Parkinson's disease (PD). To promote assessment of these often overlooked symptoms, we adapted the PD Vision Questionnaire for Internet administration. The questionnaire evaluates visual and visuospatial symptoms, impairments in activities of daily living (ADLs), and motor symptoms. PD participants of mild to moderate motor severity (n = 24) and healthy control participants (HC, n = 23) completed the questionnaire in paper and web-based formats. Reliability was assessed by comparing responses across formats. Construct validity was evaluated by reference to performance on measures of vision, visuospatial cognition, ADLs, and motor symptoms. The web-based format showed excellent reliability with respect to the paper format for both groups (all P's < 0.001; HC completing the visual and visuospatial section only). Demonstrating the construct validity of the web-based questionnaire, self-rated ADL and visual and visuospatial functioning were significantly associated with performance on objective measures of these abilities (all P's < 0.01). The findings indicate that web-based administration may be a reliable and valid method of assessing visual and visuospatial and ADL functioning in PD. C1 [Amick, Melissa M.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders, Boston, MA 02130 USA. [Amick, Melissa M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02218 USA. [Amick, Melissa M.] Brown Univ, Mem Hosp Rhode Isl, Pawtucket, RI 02860 USA. [Miller, Ivy N.; Neargarder, Sandy; Cronin-Golomb, Alice] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Neargarder, Sandy] Bridgewater State Univ, Dept Psychol, Bridgewater, MA 02325 USA. RP Amick, MM (reprint author), VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders, Boston, MA 02130 USA. EM melissa.amick@va.gov FU Michael J. Fox Foundation; NINDS [R01 NS050446] FX This study was supported by a Michael J. Fox Foundation award to M. M. Amick and by NINDS Grant R01 NS050446 to A. Cronin-Golomb. The authors thank all of the individuals who participated in this study. We are grateful to Janet Grace, Ph.D., and Joseph Friedman, M. D., for feedback during the development of this project; Karina Stavitsky, M. A., Mirella Diaz-Santos, M. A., Chelsea Toner, M. A., Dan Norton, M. A., and Thomas Laudate, Ph.D., for assistance in data collection and expert technical support; Catherine Fortier, Ph.D., and Kelvin Chou, M. D., for critical review of the paper; and Marie Saint-Hilaire, M. D., Terry Ellis MSPT, NCS, and Cathi Thomas, R.N., M. S., for aiding in recruitment efforts. They also acknowledge the important work of their web programmer Al Shaw and their web architect William F. Smith. These findings were presented in part at the annual meeting of the International Neuropsychological Society, 2011. NR 33 TC 1 Z9 1 U1 3 U2 7 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-8083 EI 2042-0080 J9 PARKINSONS DIS-US JI Parkinsons Dis. PY 2012 AR UNSP 564812 DI 10.1155/2012/564812 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 214KO UT WOS:000324132200001 ER PT J AU Bogdanova, Y Cronin-Golomb, A AF Bogdanova, Yelena Cronin-Golomb, Alice TI Neurocognitive Correlates of Apathy and Anxiety in Parkinson's Disease SO PARKINSONS DISEASE LA English DT Article ID VOXEL-BASED MORPHOMETRY; HUNTINGTONS-DISEASE; COGNITIVE FUNCTION; HIV-1 INFECTION; BASAL GANGLIA; RATING-SCALES; DEPRESSION; CIRCUITS; PERFORMANCE; PREVALENCE AB Parkinson's disease (PD) is associated with various nonmotor symptoms including neuropsychiatric and cognitive dysfunction. We examined the relation between apathy, anxiety, side of onset of motor symptoms, and cognition in PD. We hypothesized that PD patients would show different neuropsychiatric and neurocognitive profiles depending on the side of onset. 22 nondemented PD patients (11 right-side onset (RPD) with predominant left-hemisphere pathology, and 11 LPD) and 22 matched healthy controls (NC) were administered rating scales assessing apathy and anxiety, and a series of neuropsychological tests. PD patients showed a higher anxiety level than NC. There was a significant association between apathy, anxiety, and disease duration. In LPD, apathy but not anxiety was associated with performance on nonverbally mediated executive function and visuospatial measures, whereas, in RPD, anxiety but not apathy correlated with performance on verbally mediated tasks. Our findings demonstrated a differential association of apathy and anxiety to cognition in PD. C1 [Bogdanova, Yelena; Cronin-Golomb, Alice] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Bogdanova, Yelena] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Bogdanova, Yelena] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Bogdanova, Yelena] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Bogdanova, Y (reprint author), Boston Univ, Dept Psychol, 64 Cummington St, Boston, MA 02215 USA. EM bogdanov@bu.edu; alicecg@bu.edu FU National Institute of Neurological Disorders and Stroke [NIH F31 NS052131, R21 NS043730] FX This study was funded by grants to Y. Bogdanova (NIH F31 NS052131 and Sigma-Xi) and A. Cronin-Golomb (R21 NS043730) from the National Institute of Neurological Disorders and Stroke. The findings were presented in part at the annual meeting of the Society for Neuroscience, 2010. The authors thank Mirella Diaz-Santos, M.A., and Maria Valmas, M.A., for their assistance with data collection, and Chelsea Toner. M.A., for her assistance with manuscript preparation. They express appreciation to the volunteers for their participation in their study. NR 85 TC 14 Z9 14 U1 5 U2 10 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-8083 J9 PARKINSONS DIS-US JI Parkinsons Dis. PY 2012 AR UNSP 793076 DI 10.1155/2012/793076 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 214NS UT WOS:000324141200001 ER PT J AU Mikkilineni, S Cantuti-Castelvetri, I Cahill, CM Balliedier, A Greig, NH Rogers, JT AF Mikkilineni, Sohan Cantuti-Castelvetri, Ippolita Cahill, Catherine M. Balliedier, Amelie Greig, Nigel H. Rogers, Jack T. TI The Anticholinesterase Phenserine and Its Enantiomer Posiphen as 5 ' Untranslated-Region-Directed Translation Blockers of the Parkinson's Alpha Synuclein Expression SO PARKINSONS DISEASE LA English DT Article ID AMYLOID PRECURSOR PROTEIN; IRON-RESPONSIVE ELEMENT; ALZHEIMERS-DISEASE; 5'-UNTRANSLATED REGION; MESSENGER-RNA; NEURODEGENERATIVE DISEASES; ANTIPODAL ISOMERS; NONMOTOR SYMPTOMS; DEMENTIA; BETA AB There is compelling support for limiting expression of alpha-synuclein (alpha-syn) in the brains of Parkinson's disease (PD) patients. An increase of SNCA gene copy number can genetically cause familial PD where increased dose of this pathogenic protein correlates with severity of symptoms (triplication of the SNCA gene causes dementia in PD patients). Gene promoter polymorphisms were shown to increase alpha-synuclein expression as a risk for PD. Cholinesterase inhibitors can clinically slow cognitive decline in the later stages of PD etiology similar to their widespread use in Alzheimer's disease (AD). Pertinent to this, we identified that the well-tolerated anticholinesterase, phenserine, blocked neural SNCA mRNA translation and tested for targeting via its 5'untranslated region (5'UTR) in a manner similar to its action to limit the expression of the AD-specific amyloid precursor protein (APP). Posiphen, its better-tolerated (+) enantiomer (devoid of anticholinesterase action), repressed neural alpha-synuclein translation. Primary metabolic analogs of posiphen were, likewise, characterized using primary fetal neurons grown ex vivo from the brains of Parkinson's transgenic mice expressing the human SNCA gene. C1 [Mikkilineni, Sohan; Cahill, Catherine M.; Balliedier, Amelie; Rogers, Jack T.] Massachusetts Gen Hosp East, Neurochem Lab, Charlestown, MA 02129 USA. [Cantuti-Castelvetri, Ippolita] Massachusetts Gen Hosp, MIND, Charlestown, MA 02129 USA. [Greig, Nigel H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Rogers, JT (reprint author), Massachusetts Gen Hosp East, Neurochem Lab, CNY2,149,13th St, Charlestown, MA 02129 USA. EM jrogers@partners.org FU Michael J. Fox Foundation Novel Drug Discoveries Award; National Institute of Aging [R01 AG20181]; NINDS [R21NS059434]; Alzheimer's Association Zenith Award [09-131352]; Intramural Research Program, National Institute on Aging, National Institutes of Health; I. Cantuti-Caselvetri: the MGH/MIT Morris Udall Center of Excellence in PD Research [NIH NS38372]; APDA Advanced Center for Parkinson Research at MGH; NIH [HD012437 29 S-1] FX The authors thank Prof. Robert Nussbaum and Dr. Yien-Ming Kuo (UCSF) for their PAC-Tg(SNCA) mice. This research was supported (i) for J. T. Rogers by the Michael J. Fox Foundation Novel Drug Discoveries Award, National Institute of Aging R01 AG20181, NINDS R21NS059434, Alzheimer's Association Zenith Award 09-131352 and ISOA (ii) for N. H. Greig by the Intramural Research Program, National Institute on Aging, National Institutes of Health, (iii) for I. Cantuti-Caselvetri: the MGH/MIT Morris Udall Center of Excellence in PD Research (NIH NS38372) and the APDA Advanced Center for Parkinson Research at MGH, and (iv) for C. M. Cahill by NIH HD012437 29 S-1. NR 62 TC 4 Z9 4 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-8083 J9 PARKINSONS DIS-US JI Parkinsons Dis. PY 2012 AR UNSP 142372 DI 10.1155/2012/142372 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 214CP UT WOS:000324108600001 ER PT J AU Vassar, SD Bordelon, YM Hays, RD Diaz, N Rausch, R Mao, C Vickrey, BG AF Vassar, Stefanie D. Bordelon, Yvette M. Hays, Ron D. Diaz, Natalie Rausch, Rebecca Mao, Cherry Vickrey, Barbara G. TI Confirmatory Factor Analysis of the Motor Unified Parkinson's Disease Rating Scale SO PARKINSONS DISEASE LA English DT Article ID MDS-UPDRS; SECTION; FIT AB The motor examination section of the unified Parkinson's disease rating scale (UPDRS) is widely used in research but few studies have examined whether subscales exist that tap relatively distinct motor abnormalities. We analyzed data from 193 persons enrolled in a population-based study in Central California. Patients were examined after overnight PD medication washout ("OFF" state) and approximately one hour after taking medication ("ON" state). We performed confirmatory factor analysis of the UPDRS for OFF and ON state examinations; correlations, reliability, and relative validity of resulting subscales were evaluated. A model with five factors (gait/posture, tremor, rigidity, bradykinesia affecting the left extremities, bradykinesia affecting the right extremities) fit the data well, with similar results for OFF and ON states. Internal consistency reliability coefficients were 0.90 or higher for all subscales. The gait/posture subscale most strongly discriminated across levels of patient reported PD symptom severity and of how PD affects them on a daily basis. Compared to the right sided bradykinesia subscale, the left sided bradykinesia subscale had higher discrimination across levels of self-reported PD symptom severity and functional impairment. This supports motor UPDRS containing multiple subscales that can be analyzed separately and provide information distinct from the total score that may be useful in clinical studies. C1 [Vassar, Stefanie D.; Bordelon, Yvette M.; Rausch, Rebecca; Mao, Cherry; Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Vassar, Stefanie D.; Vickrey, Barbara G.] VA Greater Los Angeles Healthcare Syst, Parkinsons Dis Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. [Hays, Ron D.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Dept Med, Los Angeles, CA 90095 USA. [Hays, Ron D.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Hays, Ron D.] RAND Corp, Santa Monica, CA 90407 USA. [Diaz, Natalie] Harbor UCLA Med Ctr, Dept Neurol, Torrance, CA 90502 USA. RP Vickrey, BG (reprint author), Univ Calif Los Angeles, Dept Neurol, Box 951769,C109 RNRC, Los Angeles, CA 90095 USA. EM bvickrey@ucla.edu FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS038367]; Veterans Administration through its Southwest Parkinson's Disease Research, Education, and Clinical Center (PADRECC); NIA [P30-AG021684]; NIMHD [2P20MD000182] FX The research presented here was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke for the University of California Los Angeles UDALL Parkinson's Disease Center of Excellence (NS038367), and by the Veterans Administration through its Southwest Parkinson's Disease Research, Education, and Clinical Center (PADRECC). R. H. Hays was also supported in part by Grants from the NIA (P30-AG021684) and the NIMHD (2P20MD000182). The authors thank Jeff Bronstein, MD, PhD for assisting in UPDRS data collection and Aaron Cook, MPH, for technical assistance in paper preparation. NR 27 TC 0 Z9 0 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-8083 J9 PARKINSONS DIS-US JI Parkinsons Dis. PY 2012 AR UNSP 719167 DI 10.1155/2012/719167 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 214MK UT WOS:000324137400001 ER PT J AU Milwid, JM Ichimura, T Li, M Jiao, YX Lee, J Yarmush, JS Parekkadan, B Tilles, AW Bonventre, JV Yarmush, ML AF Milwid, Jack M. Ichimura, Takaharu Li, Matthew Jiao, Yunxin Lee, Jungwoo Yarmush, Joshua S. Parekkadan, Biju Tilles, Arno W. Bonventre, Joseph V. Yarmush, Martin L. TI Secreted Factors from Bone Marrow Stromal Cells Upregulate IL-10 and Reverse Acute Kidney Injury SO STEM CELLS INTERNATIONAL LA English DT Article ID MESENCHYMAL STEM-CELLS; ACUTE-RENAL-FAILURE; ACUTE TUBULAR INJURY; TGF-BETA; IN-VITRO; URINARY BIOMARKER; MOLECULE-1 KIM-1; EPITHELIAL-CELLS; RAT MODEL; CISPLATIN AB Acute kidney injury is a devastating syndrome that afflicts over 2,000,000 people in the US per year, with an associated mortality of greater than 70% in severe cases. Unfortunately, standard-of-care treatments are not sufficient for modifying the course of disease. Many groups have explored the use of bone marrow stromal cells (BMSCs) for the treatment of AKI because BMSCs have been shown to possess unique anti-inflammatory, cytoprotective, and regenerative properties in vitro and in vivo. It is yet unresolved whether the primary mechanisms controlling BMSC therapy in AKI depend on direct cell infusion, or whether BMSC-secreted factors alone are sufficient for mitigating the injury. Here we show that BMSC-secreted factors are capable of providing a survival benefit to rats subjected to cisplatin-induced AKI. We observed that when BMSC-conditioned medium (BMSC-CM) is administered intravenously, it prevents tubular apoptosis and necrosis and ameliorates AKI. In addition, we observed that BMSC-CM causes IL-10 upregulation in treated animals, which is important to animal survival and protection of the kidney. In all, these results demonstrate that BMSC-secreted factors are capable of providing support without cell transplantation, and the IL-10 increase seen in BMSC-CM-treated animals correlates with attenuation of severe AKI. C1 [Milwid, Jack M.; Li, Matthew; Jiao, Yunxin; Lee, Jungwoo; Yarmush, Joshua S.; Parekkadan, Biju; Yarmush, Martin L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Milwid, Jack M.; Bonventre, Joseph V.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Ichimura, Takaharu; Bonventre, Joseph V.] Harvard Univ, Sch Med, Renal Med Div, Brigham & Womens Hosp, Boston, MA 02115 USA. [Tilles, Arno W.] Sentien Biotechnol Inc, Dept Res & Dev, Medford, MA 02155 USA. [Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ 08901 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU National Human Genome Research Institute (NHGRI) [T32 HG002295]; National Institutes of Health [K01DK087770, R21DK085267, DK39773, DK72381]; Shriners Hospitals for Children FX This work was funded in part by Grant number T32 HG002295 from the National Human Genome Research Institute (NHGRI) (J. M. Milwid). This work was also partially supported by Grants from the National Institutes of Health: K01DK087770 (B. Parekkadan), R21DK085267 (M. L. Yarmush), DK39773, and DK72381 (J. V. Bonventre) and the Shriners Hospitals for Children (M. L. Yarmush, B. Parekkadan). NR 52 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-966X J9 STEM CELLS INT JI Stem Cells Int. PY 2012 AR UNSP 392050 DI 10.1155/2012/392050 PG 12 WC Cell & Tissue Engineering SC Cell Biology GA 209OX UT WOS:000323769500001 ER PT J AU Rutten, MJ Janes, MA Chang, IR Gregory, CR Gregory, KW AF Rutten, Michael J. Janes, Michael Ann Chang, Ivy R. Gregory, Cynthia R. Gregory, Kenton W. TI Development of a Functional Schwann Cell Phenotype from Autologous Porcine Bone Marrow Mononuclear Cells for Nerve Repair SO STEM CELLS INTERNATIONAL LA English DT Article ID MESENCHYMAL STEM-CELLS; INCREASES INTRACELLULAR CALCIUM; LARGE-ANIMAL-MODELS; IN-VITRO; STROMAL CELLS; PURINERGIC RECEPTORS; RAT VIBRISSAE; AXON FUNCTION; SPINAL-CORD; DIFFERENTIATION AB Adult bone marrow mononuclear cells (BM-MNCs) are a potential resource for making Schwann cells to repair damaged peripheral nerves. However, many methods of producing Schwann-like cells can be laborious with the cells lacking a functional phenotype. The objective of this study was to develop a simple and rapid method using autologous BM-MNCs to produce a phenotypic and functional Schwann-like cell. Adult porcine bone marrow was collected and enriched for BM-MNCs using a SEPAX device, then cells cultured in Neurobasal media, 4 mM L-glutamine and 20% serum. After 6-8 days, the cultures expressed Schwann cell markers, S-100, O4, GFAP, were FluoroMyelin positive, but had low p75(NGF) expression. Addition of neuregulin (1-25 nM) increased p75(NGF) levels at 24-48 hrs. We found ATP dose-dependently increased intracellular calcium [Ca2+](i), with nucleotide potency being UTP = ATP > ADP > AMP > adenosine. Suramin blocked the ATP-induced [Ca2+](i) but alpha,beta,-methylene-ATP had little effect suggesting an ATP purinergic P2Y2 G-protein-coupled receptor is present. Both the Schwann cell markers and ATP-induced [Ca2+](i) sensitivity decreased in cells passaged >20 times. Our studies indicate that autologous BM-MNCs can be induced to form a phenotypic and functional Schwann-like cell which could be used for peripheral nerve repair. C1 [Rutten, Michael J.; Janes, Michael Ann; Chang, Ivy R.; Gregory, Kenton W.] Providence Hlth & Serv, Portland, OR 97225 USA. [Rutten, Michael J.; Gregory, Cynthia R.; Gregory, Kenton W.] Oregon Hlth & Sci Univ, OHSU Ctr Regenerat Med, Portland, OR 97239 USA. [Gregory, Cynthia R.] Oregon Biomed Engn Inst, Wilsonville, OR 97070 USA. [Gregory, Cynthia R.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Rutten, MJ (reprint author), Providence Hlth & Serv, 9555 SW Barnes Rd, Portland, OR 97225 USA. EM ruttenm@ohsu.edu FU Department of the Army [W81XWH-05-1-0586, W81XWH-09-1-0688]; Inskeep and Loacker philanthropic FX They would like to thank Rebecca Sarao, Ping-Cheng Wu, and Jeffrey Teach for the collection of the bone marrow samples, and Lian Wang and Ann Romer for assistance with the SEPAX bone marrow mononuclear cell purification. They would also like to thank Dr. Daniel Beacham (Molecular Probes/Invitrogen) with advice in the early part of these studies on ATP receptors and intracellular calcium regulation in Schwann cells. The Department of the Army Grants no. W81XWH-05-1-0586, W81XWH-09-1-0688, and Inskeep and Loacker philanthropic donations funded this work. The content of the information does not necessarily reflect the position of the Federal Government and no official endorsement should be inferred. NR 75 TC 1 Z9 1 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2012 AR UNSP 738484 DI 10.1155/2012/738484 PG 15 WC Cell & Tissue Engineering SC Cell Biology GA 209RL UT WOS:000323777400001 ER PT J AU Sheridan, SD Surampudi, V Rao, RR AF Sheridan, Steven D. Surampudi, Vasudha Rao, Raj R. TI Analysis of Embryoid Bodies Derived from Human Induced Pluripotent Stem Cells as a Means to Assess Pluripotency SO STEM CELLS INTERNATIONAL LA English DT Review ID IN-VITRO DIFFERENTIATION; SUSPENSION-CULTURE; ENHANCED DIFFERENTIATION; BODY FORMATION; SOMATIC-CELLS; GROWTH-FACTOR; EXPRESSION; SYSTEM; MICROGRAVITY; EFFICIENCY AB Human induced pluripotent stem cells (hiPSCs) have core properties of unlimited self-renewal and differentiation potential and have emerged as exciting cell sources for applications in regenerative medicine, drug discovery, understanding of development, and disease etiology. Key among numerous criteria to assess pluripotency includes the in vivo teratoma assay that has been widely proposed as a standard functional assay to demonstrate the pluripotency of hiPSCs. Yet, the lack of reliability across methodologies, lack of definitive clinical significance, and associated expenses bring into question use of the teratoma assay as the "gold standard" for determining pluripotency. We propose use of the in vitro embryoid body (EB) assay as an important alternative to the teratoma assay. This paper summarizes the methodologies for creating EBs from hiPSCs and the subsequent analyses to assess pluripotency and proposes its use as a cost-effective, controlled, and reproducible approach that can easily be adopted to determine pluripotency of generated hiPSCs. C1 [Sheridan, Steven D.] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Surampudi, Vasudha; Rao, Raj R.] Virginia Commonwealth Univ, Dept Chem & Life Sci Engn, Sch Engn, Richmond, VA 23284 USA. RP Rao, RR (reprint author), Virginia Commonwealth Univ, Dept Chem & Life Sci Engn, Sch Engn, Med Coll Virginia Campus, Richmond, VA 23284 USA. EM rrrao@vcu.edu FU NSF-CAREER [074556] FX Partial funding for this work was provided by NSF-CAREER 074556 (R. Rao). NR 63 TC 2 Z9 2 U1 0 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-966X J9 STEM CELLS INT JI Stem Cells Int. PY 2012 AR UNSP 738910 DI 10.1155/2012/738910 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 209RM UT WOS:000323777600001 ER PT J AU Bird, TD AF Bird, Thomas D. BE Wood, NW TI The future of neurogenetics SO NEUROGENETICS: A GUIDE FOR CLINICIANS LA English DT Article; Book Chapter C1 [Bird, Thomas D.] Univ Washington, Dept Neurol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Bird, Thomas D.] Univ Washington, Dept Med Genet, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Bird, TD (reprint author), Univ Washington, Dept Neurol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-54372-9 PY 2012 BP 229 EP 233 D2 10.1017/CBO9781139087711 PG 5 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA BFZ95 UT WOS:000322012800015 ER PT J AU Solnica, B Skupien, J Kusnierz-Cabala, B Slowinska-Solnica, K Witek, P Cempa, A Malecki, MT AF Solnica, Bogdan Skupien, Jan Kusnierz-Cabala, Beata Slowinska-Solnica, Krystyna Witek, Przemyslaw Cempa, Agnieszka Malecki, Maciej T. TI The effect of hematocrit on the results of measurements using glucose meters based on different techniques SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE diabetes mellitus; glucose meters; point-of-care testing; self-monitored blood glucose ID VALUES AB Background: The aim of the study was to evaluate the effect of hematocrit (HCT) on glucose meter assays based on different measurement techniques. Methods: This paper studied glucose meters utilizing the glucose dehydrogenase reaction and four measurement techniques: colorimetry (HemoCue), reflectometry (Accu-Chek Active), amperometry (Optium Xido) and coulometry (Optium Omega). The EDTA venous blood samples HCT were modified by adding or removing defined aliquots of plasma. Glucose concentration was measured using each meter in 27 batches of blood samples, with HCT ranging from 20% to 60% in 10% increments. The data were analyzed using repeated measures models and a linear random effects model. Results: A significant relationship between HCT and glucose reading in all meters was found and, for all meters except Optium Xido, there was a significant modification of this relationship by glucose level. The relative decrease in glucose concentration per 1% increase of the HCT value varied from 0.30% for Optium Omega in samples with glucose concentrations <5.55 mmol/L to 1.37% for Optium Xido in the same stratum (p<0.0001). The 5% glucose meter error (the ADA recommendation) was reached in the <5.55 mmol/L stratum after HCT change by 3.9%-16.7%. Conclusions: There is a significant continuous effect of HCT on measurement accuracy of glucose meters across its wide range of values and glucose concentrations. The most sensitive to the HCT interference was the system utilizing amperometric technique (Optium Xido) followed by the one with reflectometric technique (Accu-Chek Active), while the systems with the coulometric technique (Optium Omega) or colorimetric measurements in whole blood haemolysate (HemoCue) were less sensitive. C1 [Solnica, Bogdan; Kusnierz-Cabala, Beata; Slowinska-Solnica, Krystyna] Jagiellonian Univ, Coll Med, Dept Diagnost, PL-31501 Krakow, Poland. [Skupien, Jan] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Witek, Przemyslaw; Malecki, Maciej T.] Jagiellonian Univ, Coll Med, Dept Metab Dis, PL-31501 Krakow, Poland. [Witek, Przemyslaw; Cempa, Agnieszka; Malecki, Maciej T.] Univ Hosp, Krakow, Poland. RP Solnica, B (reprint author), Jagiellonian Univ, Coll Med, Dept Diagnost, 15A Kopernika St, PL-31501 Krakow, Poland. EM mbsolnic@cyf-kr.edu.pl NR 11 TC 4 Z9 4 U1 2 U2 9 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PY 2012 VL 50 IS 2 BP 361 EP 365 DI 10.1515/CCLM.2011.770 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 914ZB UT WOS:000301991300023 ER PT B AU Mehta, DD Listfield, RW Cheyne, HA Heaton, JT Feng, SW Zanartu, M Hillman, RE AF Mehta, Daryush D. Listfield, Rebecca Woodbury Cheyne, Harold A., II Heaton, James T. Feng, Shengran W. Zanartu, Matias Hillman, Robert E. GP International Speech Communications Association TI Duration of ambulatory monitoring needed to accurately estimate voice use SO 13TH ANNUAL CONFERENCE OF THE INTERNATIONAL SPEECH COMMUNICATION ASSOCIATION 2012 (INTERSPEECH 2012), VOLS 1-3 LA English DT Proceedings Paper CT 13th Annual Conference of the International-Speech-Communication-Association CY SEP 09-13, 2012 CL Portland, OR SP Int Speech Commun Assoc DE ambulatory voice monitoring; voice use; voice disorders; accelerometer ID ACCUMULATOR AB Voice use is considered to play a major role in the development of many voice disorders, and clinicians focus on evaluating and modifying how patients use their voices throughout the day. Some voice monitoring devices have used neck-mounted accelerometers to unobtrusively and confidentially track voice use related measures, such as phonation time, fundamental frequency, and sound intensity. Guidelines for the clinical use of such monitoring devices have yet to be established. This is a preliminary investigation into establishing initial benchmarks for obtaining robust estimates of long-term average voice use that may be used to begin examining basic relationships between vocal loading and voice use related pathology. As expected, adequate monitoring durations depend on the inherent variability of the parameter of interest, with much of the error decreased after 26 hours of monitoring. Investigations are currently under way to take advantage of a smartphone-based voice monitoring system that is designed to enhance device wearability and enable the derivation of new clinically relevant measures. C1 [Mehta, Daryush D.; Listfield, Rebecca Woodbury; Heaton, James T.; Feng, Shengran W.; Hillman, Robert E.] Mass Gen Hosp, Ctr Laryngeal Surg & Voice Rehab, Boston, MA USA. RP Mehta, DD (reprint author), Mass Gen Hosp, Ctr Laryngeal Surg & Voice Rehab, Boston, MA USA. EM daryush.mehta@alum.mit.edu; woodbury@alum.mit.edu; hac68@cornell.edu; james.heaton@mgh.harvard.edu; willfeng@mit.edu; matias.zanartu@usm.cl; hillman.robert@mgh.harvard.edu NR 17 TC 0 Z9 0 U1 0 U2 4 PU ISCA-INT SPEECH COMMUNICATION ASSOC PI BAIXAS PA C/O EMMANUELLE FOXONET, 4 RUE DES FAUVETTES, LIEU DIT LOUS TOURILS, BAIXAS, F-66390, FRANCE BN 978-1-62276-759-5 PY 2012 BP 1334 EP 1337 PG 4 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BFO97 UT WOS:000320827200334 ER PT J AU Palmer, KL Godfrey, P Griggs, A Kos, VN Zucker, J Desjardins, C Cerqueira, G Gevers, D Walker, S Wortman, J Feldgarden, M Haas, B Birren, B Gilmore, MS AF Palmer, Kelli L. Godfrey, Paul Griggs, Allison Kos, Veronica N. Zucker, Jeremy Desjardins, Christopher Cerqueira, Gustavo Gevers, Dirk Walker, Suzanne Wortman, Jennifer Feldgarden, Michael Haas, Brian Birren, Bruce Gilmore, Michael S. TI Comparative Genomics of Enterococci: Variation in Enterococcus faecalis, Clade Structure in E. faecium, and Defining Characteristics of E. gallinarum and E. casseliflavus SO MBIO LA English DT Article ID PATHOGENICITY ISLAND; STREPTOCOCCUS-FAECALIS; STAPHYLOCOCCUS-AUREUS; PHYLOGENETIC ANALYSES; LIPOTEICHOIC ACID; GENE-CLUSTER; BIOSYNTHESIS; RESISTANCE; VIRULENCE; PROTEIN AB The enterococci are Gram-positive lactic acid bacteria that inhabit the gastrointestinal tracts of diverse hosts. However, Enterococcus faecium and E. faecalis have emerged as leading causes of multidrug-resistant hospital-acquired infections. The mechanism by which a well-adapted commensal evolved into a hospital pathogen is poorly understood. In this study, we examined high-quality draft genome data for evidence of key events in the evolution of the leading causes of enterococcal infections, including E. faecalis, E. faecium, E. casseliflavus, and E. gallinarum. We characterized two clades within what is currently classified as E. faecium and identified traits characteristic of each, including variation in operons for cell wall carbohydrate and putative capsule biosynthesis. We examined the extent of recombination between the two E. faecium clades and identified two strains with mosaic genomes. We determined the underlying genetics for the defining characteristics of the motile enterococci E. casseliflavus and E. gallinarum. Further, we identified species-specific traits that could be used to advance the detection of medically relevant enterococci and their identification to the species level. IMPORTANCE The enterococci, in particular, vancomycin-resistant enterococci, have emerged as leading causes of multidrug-resistant hospital-acquired infections. In this study, we examined genome sequence data to define traits with the potential to influence host-microbe interactions and to identify sequences and biochemical functions that could form the basis for the rapid identification of enterococcal species or lineages of importance in clinical and environmental samples. C1 [Palmer, Kelli L.; Kos, Veronica N.; Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [Palmer, Kelli L.; Kos, Veronica N.; Walker, Suzanne; Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA USA. [Palmer, Kelli L.; Kos, Veronica N.; Gilmore, Michael S.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Palmer, Kelli L.; Kos, Veronica N.; Gilmore, Michael S.] Harvard Microbial Sci Initiat, Cambridge, MA USA. [Godfrey, Paul; Griggs, Allison; Kos, Veronica N.; Zucker, Jeremy; Desjardins, Christopher; Cerqueira, Gustavo; Gevers, Dirk; Wortman, Jennifer; Feldgarden, Michael; Haas, Brian; Birren, Bruce; Gilmore, Michael S.] Broad Inst, Cambridge, MA USA. RP Gilmore, MS (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. EM michael_gilmore@meei.harvard.edu RI Zucker, Jeremy/M-3643-2016; OI Zucker, Jeremy/0000-0002-7276-9009; Wortman, Jennifer/0000-0002-8713-1227 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Department of Health and Human Services [AI072360]; Harvard-Wide Antibiotic Resistance Program [AI083214, HHSN272200900018C]; NIH [EY007145, EY020734] FX This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Department of Health and Human Services, under grant AI072360, the Harvard-Wide Antibiotic Resistance Program (AI083214), and contract no. HHSN272200900018C. Additionally, K. L. P. was supported by NIH fellowships EY007145 and EY020734. NR 68 TC 44 Z9 44 U1 0 U2 17 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2012 VL 3 IS 1 AR e00318-11 DI 10.1128/mBio.00318-11 PG 11 WC Microbiology SC Microbiology GA 933AK UT WOS:000303331400025 PM 22354958 ER PT J AU Saleem, S Pacula, M Chasin, R Kumar, R Prasad, R Crystal, M Marx, B Sloan, D Vasterling, J Speroff, T AF Saleem, Shirin Pacula, Maciej Chasin, Rachel Kumar, Rohit Prasad, Rohit Crystal, Michael Marx, Brian Sloan, Denise Vasterling, Jennifer Speroff, Theodore GP IEEE TI Automatic Detection of Psychological Distress Indicators in Online Forum Posts SO 2012 ASIA-PACIFIC SIGNAL AND INFORMATION PROCESSING ASSOCIATION ANNUAL SUMMIT AND CONFERENCE (APSIPA ASC) LA English DT Proceedings Paper CT Annual Summit and Conference of the Asia-Pacific-Signal-and-Information-Processing-Association (APSIPA) CY DEC 03-06, 2012 CL Hollywood, CA SP Asia Pacific Signal & Informat Proc Assoc (APSIPA) ID HEALTH AB The stigma associated with mental health issues makes face-to-face discussions with family members, friends, or medical professionals difficult for many people. In contrast, the Internet, due to its ubiquity and global outreach, is increasingly becoming a popular medium for distressed individuals to anonymously relate experiences. In this paper, we present a system for automatically detecting psychological distress indicators in informal text interactions on Internet discussion forums. We compare a suite of innovative features and classifiers on data downloaded from an online forum discussing psychological health issues. Psychologists annotated individual messages with a comprehensive set of distress labels derived from the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV. The noisy nature of the forum posts and the large set of distress labels for multi-label text classification (many of which cannot be detected by a mere surface form analysis of the text), make the task extremely challenging. A late fusion technique combines outputs from different classifiers resulting in promising accuracy on this challenging multi-label classification problem. C1 [Saleem, Shirin; Pacula, Maciej; Kumar, Rohit; Prasad, Rohit; Crystal, Michael] Raytheon BBN Technol, Waltham, MA 02451 USA. [Chasin, Rachel] MIT, Cambridge, MA 02139 USA. [Marx, Brian; Sloan, Denise; Vasterling, Jennifer] Boston Univ Sch Med, VA Boston Healthcare Sytem, Natl Ctr PTSD, Boston, MA USA. [Speroff, Theodore] Vanderbilt Univ, VA Tennessee Valley Healthcare Syst, Sch Med, Nashville, TN USA. RP Saleem, S (reprint author), Raytheon BBN Technol, Waltham, MA 02451 USA. EM ssaleem@bbn.com; mpacula@bbn.com; rchasin@mit.edu; rkumar@bbn.com; rprasad@bbn.com; mcrystal@bbn.com; brian.marx@va.gov; denise.sloan@va.gov; jennifer.vasterling@va.gov; ted.speroff@vanderbilt.edu FU DARPA DCAPS Program FX This paper is based upon work supported by the DARPA DCAPS Program. The views expressed here are those of the author(s) and do not reflect the official policy or position of the Department of Defense or the U.S. Government. NR 19 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-4863-8 PY 2012 PG 4 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA BFE52 UT WOS:000319456200253 ER PT S AU Deng, YB Colby, G Heaton, JT Meltzner, GS AF Deng, Yunbin Colby, Glen Heaton, James T. Meltzner, Geoffrey S. GP IEEE TI Signal Processing Advances for the MUTE sEMG-Based Silent Speech Recognition System SO 2012 IEEE MILITARY COMMUNICATIONS CONFERENCE (MILCOM 2012) SE IEEE Military Communications Conference LA English DT Proceedings Paper CT IEEE Military Communications Conference (MILCOM) CY OCT 29-NOV 01, 2012 CL Orlando, FL SP IEEE, AFCEA Int, IEEE Commun Soc DE sEMG speech detection; sEMG speech recognition; silent speech communication; sub-word sEMG model; speaker adaptive sEMG feature extraction AB Military speech communication often needs to be conducted in very high noise environments. In addition, there are scenarios, such as special-ops missions, for which it is beneficial to have covert voice communications. To enable both capabilities, we have developed the MUTE (Mouthed-speech Understanding and Transcription Engine) system, which bypasses the limitations of traditional acoustic speech communication by measuring and interpreting muscle activity of the facial and neck musculature involved in silent speech production. This article details our recent progress on automatic surface electromyography (sEMG) speech activity detection, feature parameterization, multi-task sEMG corpus development, context dependent sub-word sEMG modeling, discriminative phoneme model training, and flexible vocabulary continuous sEMG silent speech recognition. Our current system achieved recognition accuracy at developable levels for a pre-defined special ops task We further propose research directions in adaptive sEMG feature parameterization and data driven decision question generation for context-dependent sEMG phoneme modeling. C1 [Deng, Yunbin; Colby, Glen; Meltzner, Geoffrey S.] BAE Syst Inc, Burlington, MA 01803 USA. [Heaton, James T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Deng, YB (reprint author), BAE Syst Inc, Burlington, MA 01803 USA. EM Yunbin.deng@baesystems.com FU United States Defense Advanced Research Projects Agency ( DARPA) Information Innovation Office ( I2O) Program FX This study was sponsored by the United States Defense Advanced Research Projects Agency ( DARPA) Information Innovation Office ( I2O) Program, " Advanced Speech Encoding." The views and conclusions in this document are those of the authors and should not be interpreted as representing the official policies, either expressly or implied, of DARPA or the U. S. Government. NR 21 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2155-7578 BN 978-1-4673-1729-0; 978-1-4673-1730-6 J9 IEEE MILIT COMMUN C PY 2012 PG 6 WC Telecommunications SC Telecommunications GA BEY60 UT WOS:000318702900221 ER PT S AU Naeser, M Ho, M Martin, P Treglia, E Krengel, M Hamblin, M Baker, E AF Naeser, M. Ho, M. Martin, P. Treglia, E. Krengel, M. Hamblin, M. Baker, E. BE Miozzo, M TI Improved Language after Scalp Application of Red/Near-infrared Light-Emitting Diodes: Pilot Study supporting a New, Noninvasive Treatment for Chronic Aphasia SO 50TH ACADEMY OF APHASIA MEETING SE Procedia Social and Behavioral Sciences LA English DT Proceedings Paper CT 50th Academy-of-Aphasia Meeting CY OCT 28-30, 2012 CL San Francisco, CA SP Acad Aphasia C1 [Naeser, M.; Ho, M.; Martin, P.; Treglia, E.; Krengel, M.; Baker, E.] VA Boston Healthcare Syst, Boston, MA USA. EM mnaeser@bu.edu NR 6 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-0428 J9 PROCD SOC BEHV PY 2012 VL 61 BP 138 EP 139 DI 10.1016/j.sbspro.2012.10.116 PG 2 WC Audiology & Speech-Language Pathology; Clinical Neurology; Rehabilitation SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Rehabilitation GA BFV52 UT WOS:000321555700068 ER PT S AU Lim, K McNeil, M Dickey, M Doyle, P Hula, W AF Lim, K. McNeil, M. Dickey, M. Doyle, P. Hula, W. BE Miozzo, M TI Conflict Resolution and Goal Maintenance Components of Executive Attention are Impaired in Persons With Aphasia: Evidence from the Picture-Word Interference Task SO 50TH ACADEMY OF APHASIA MEETING SE Procedia Social and Behavioral Sciences LA English DT Proceedings Paper CT 50th Academy-of-Aphasia Meeting CY OCT 28-30, 2012 CL San Francisco, CA SP Acad Aphasia C1 [Lim, K.; Doyle, P.; Hula, W.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. EM limky21@gmail.com OI Dickey, Michael Walsh/0000-0002-9068-3313 NR 2 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-0428 J9 PROCD SOC BEHV PY 2012 VL 61 BP 181 EP 182 DI 10.1016/j.sbspro.2012.10.137 PG 2 WC Audiology & Speech-Language Pathology; Clinical Neurology; Rehabilitation SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Rehabilitation GA BFV52 UT WOS:000321555700089 ER PT S AU Cohen, AD Rabinovici, GD Mathis, CA Jagust, WJ Klunk, WE Ikonomovic, MD AF Cohen, Ann D. Rabinovici, Gil D. Mathis, Chester A. Jagust, William J. Klunk, William E. Ikonomovic, Milos D. BE Michaelis, EK Michaelis, ML TI Using Pittsburgh Compound B for In Vivo PET Imaging of Fibrillar Amyloid-Beta SO CURRENT STATE OF ALZHEIMER'S DISEASE RESEARCH AND THERAPEUTICS SE Advances in Pharmacology LA English DT Article; Book Chapter ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; ALZHEIMERS ASSOCIATION WORKGROUPS; FRONTOTEMPORAL LOBAR DEGENERATION; PRIMARY-PROGRESSIVE-APHASIA; APOLIPOPROTEIN-E GENOTYPE; LEWY BODY DEMENTIA; PARKINSONS-DISEASE DEMENTIA; CEREBROSPINAL-FLUID MARKERS; CEREBRAL GLUCOSE-METABOLISM AB The development of A beta-PET imaging agents has allowed for detection of fibrillar A beta deposition in vivo and marks a major advancement in understanding the role of A beta in Alzheimer's disease (AD). Imaging A beta thus has many potential clinical benefits: early or perhaps preclinical detection of disease and accurately distinguishing AD from dementias of other non-A beta causes in patients presenting with mild or atypical symptoms or confounding comorbidities (in which the distinction is difficult to make clinically). From a research perspective, imaging A beta allows us to study relationships between amyloid pathology and changes in cognition, brain structure, and function across the continuum from normal aging to mild cognitive impairment (MCI) to AD; and to monitor the effectiveness of anti-A beta drugs and relate them to neurodegeneration and clinical symptoms. Here, we will discuss the application of one of the most broadly studied and widely used A beta imaging agents, Pittsburgh Compound-B (PiB). C1 [Cohen, Ann D.; Klunk, William E.; Ikonomovic, Milos D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Rabinovici, Gil D.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA. [Mathis, Chester A.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. [Jagust, William J.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Klunk, William E.; Ikonomovic, Milos D.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Cohen, AD (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. OI Klunk, William/0000-0001-5512-0251 FU NIA NIH HHS [P01 AG025204, R01 AG018402, R01 AG18402, P50 AG005133, R37 AG025516, AG014449, P01 AG014449, RF1 AG025516, AG034570, K23 AG031861, R01 AG034570, K01 AG037562] NR 278 TC 31 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1054-3589 BN 978-0-12-394845-8 J9 ADV PHARMACOL JI Adv. Pharmacol. PY 2012 VL 64 BP 27 EP 81 DI 10.1016/B978-0-12-394816-8.00002-7 PG 55 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA BFX20 UT WOS:000321744100002 PM 22840744 ER PT S AU Yu, M Cantor, AB AF Yu, Ming Cantor, Alan B. BE Gibbins, JM MahautSmith, MP TI Megakaryopoiesis and Thrombopoiesis: An Update on Cytokines and Lineage Surface Markers SO PLATELETS AND MEGAKARYOCYTES, VOL 3: ADDITIONAL PORTOCOLS AND PERSPECTIVES SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Megakaryopoiesis; Thrornbopoietin; Hematopoietic stem cells; Thrombopoiesis; c-Mpl; Megakaryocyte; Megakaryocyte progenitor; Cytokine; Surface marker; CD41 ID HEMATOPOIETIC STEM-CELLS; DEMARCATION MEMBRANE SYSTEM; C-MPL LIGAND; CHEMOKINE RECEPTOR CXCR4; BONE-MARROW; IN-VITRO; MEGAKARYOCYTE PROGENITORS; PLATELET PRODUCTION; DEFICIENT MICE; MAST-CELLS AB Megakaryopoiesis is the process by which mature megakaryocytes (MKs) develop from hematopoietic stem cells (HSCs). The biological function of MKs is to produce platelets, which play critical roles in hemostasis and contribute to angiogenesis and wound healing. The generation of platelets from MKs is termed thrombopoiesis. The cytokine thrombopoietin (TPO) is the major regulator of megakaryopoiesis and thrombopoiesis. It binds to its surface receptor, c-Mpl, and acts through multiple downstream signaling pathways, including the PI-3 kinase-Akt, MAPK, and ERK1/ERK2 pathways. However, non-TPO pathways, such as the SDF1/CXCR4 axis, Notch signaling, src family kinases, integrin signaling, and Platelet Factor 4/low-density lipoprotein receptor-related protein 1, have more recently been recognized to influence megakaryopoiesis and thrombopoiesis in vitro and in vivo. In this chapter, we review megakaryopoiesis and thrombopoiesis with emphasis on cell surface marker changes during their differentiation from HSCs, and the classical cytokines that affect these developmental stages. We also discuss non-TPO regulators and their effects on in vitro culture systems. C1 [Yu, Ming] Rockefeller Univ, Labs Biochem & Mol Biol, New York, NY 10021 USA. [Cantor, Alan B.] Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. [Cantor, Alan B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yu, M (reprint author), Rockefeller Univ, Labs Biochem & Mol Biol, 1230 York Ave, New York, NY 10021 USA. NR 75 TC 11 Z9 12 U1 2 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-307-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 788 BP 291 EP 303 DI 10.1007/978-1-61779-307-3_20 D2 10.1007/978-1-61779-307-3 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFY20 UT WOS:000321874900021 PM 22130715 ER PT S AU Zhu, SZ Low, BC AF Zhu, Shizhen Low, Boon Chuan BE Rivero, F TI Using Zebrafish for Studying Rho GTPases Signaling In Vivo SO RHO GTPASES: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Rho small GTPase; Zebrafish; Mopholino oligos; mRNA rescue; Microinjection; In situ hybridization; Western blot; Small molecule inhibitor ID GENE-EXPRESSION; DRUG DISCOVERY; HUMAN-DISEASE; MODEL SYSTEM; EMBRYOS; MIGRATION; MICROINJECTION; GASTRULATION; PATHWAY; PROTEIN AB Rho small GTPases play pivotal roles in a variety of dynamic cellular processes including cytoskeleton rearrangement, cell migration, cell proliferation, cell survival, and gene regulation. However, their functions in vivo are much less understood. Recently, the zebrafish, Danio rerio, has emerged as a powerful model organism for developmental and genetic studies. Zebrafish embryos have many unique characteristics, such as optical transparency, external fertilization and development, and amenability for various molecular manipulations including morpholino oligo-mediated gene knockdown, mRNA or DNA overexpression-induced gain of function or rescue, in situ hybridization (ISH) with riboprobes for gene expression, western blot for protein analysis, small-molecule inhibition on signaling pathways, and bioimaging for tracking of molecular events. Taking many of such advantages, we have demonstrated the role of rhoA small GTPase in the control of gastrulation cell movements and cell survival during early zebrafish embryogenesis, linking RhoA functions to at least the noncanonical Wnt, Mek/Erk, and Bcl2 signaling nodes in vivo. Here, we describe the use of such techniques, including gene knockdown by morpholino oligo, functional rescue by mRNA overexpression, microinjection, ISH, western blot analysis and pharmacological inhibition of signaling pathways by small molecule inhibitors, with special considerations on their merits, potential drawbacks, and adaptation which could pave the way to our better understanding of the roles of various classes of small GTPases in regulating cell dynamics and development in vivo. C1 [Zhu, Shizhen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Low, Boon Chuan] Natl Univ Singapore, Cell Signaling & Dev Biol Lab, Dept Biol Sci, Mechanobiol Inst, Singapore 117548, Singapore. RP Zhu, SZ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 32 TC 1 Z9 1 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-441-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 827 BP 321 EP 337 DI 10.1007/978-1-61779-442-1_21 D2 10.1007/978-1-61779-441-4 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA BFY92 UT WOS:000321932700022 PM 22144284 ER PT J AU Schmahmann, JD AF Schmahmann, Jeremy D. BE Caplan, LR VanGijn, J TI Cognitive and behavioral manifestations of cerebellar strokes: their relation to motor control and functional topography in the cerebellum SO STROKE SYNDROMES, 3RD EDITION LA English DT Article; Book Chapter ID ARTERY TERRITORY INFARCTS; FOU RIRE PRODROMIQUE; ATAXIA RATING-SCALE; RHESUS-MONKEY; BASIS PONTIS; PATHOLOGICAL LAUGHTER; PREFRONTAL CORTEX; WORKING-MEMORY; LATERAL BRANCH; CASE SERIES C1 Harvard Univ, Sch Med, Dept Neurol,Lab Neuroanat & Cerebellar Neurobiol, Massachusetts Gen Hosp,Ataxia Unit,Cognit & Behav, Boston, MA 02115 USA. RP Schmahmann, JD (reprint author), Harvard Univ, Sch Med, Dept Neurol,Lab Neuroanat & Cerebellar Neurobiol, Massachusetts Gen Hosp,Ataxia Unit,Cognit & Behav, Boston, MA 02115 USA. NR 154 TC 0 Z9 0 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-01886-0 PY 2012 BP 32 EP 51 D2 10.1017/CBO9781139093286 PG 20 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA BFU78 UT WOS:000321487400004 ER PT J AU Wray, SH Caplan, LR AF Wray, Shirley H. Caplan, Louis R. BE Caplan, LR VanGijn, J TI Visual symptoms (eye) SO STROKE SYNDROMES, 3RD EDITION LA English DT Article; Book Chapter ID ISCHEMIC OPTIC NEUROPATHY; RETINAL ARTERY-OCCLUSION; TRANSIENT MONOCULAR BLINDNESS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; AMAUROSIS FUGAX; ANTIPHOSPHOLIPID ANTIBODIES; CAROTID-ARTERY; COHERENCE TOMOGRAPHY; ANTICARDIOLIPIN ANTIBODIES; CEREBROVASCULAR-DISEASE C1 [Wray, Shirley H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wray, Shirley H.] Massachusetts Gen Hosp, Dept Neurol, Unit Neurovisual Disorders, Boston, MA 02114 USA. [Caplan, Louis R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Sch Med, Boston, MA 02215 USA. RP Wray, SH (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 153 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-01886-0 PY 2012 BP 98 EP 116 D2 10.1017/CBO9781139093286 PG 19 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA BFU78 UT WOS:000321487400008 ER PT J AU Brady, ST Siegel, GJ Albers, RW Price, D Benjamins, J Fisher, S Hall, A Bazan, N Coyle, J Sisodia, S AF Brady, Scott T. Siegel, George J. Albers, R. Wayne Price, Donald Benjamins, Joyce Fisher, Stephen Hall, Alison Bazan, Nicolas Coyle, Joseph Sisodia, Sangram BE Brady, ST Siegel, GJ Albers, RW Price, DL TI Eighth Edition Acknowledgments and History SO BASIC NEUROCHEMISTRY: PRINCIPLES OF MOLECULAR, CELLULAR, AND MEDICAL NEUROBIOLOGY, 8THEDITION LA English DT Editorial Material; Book Chapter C1 [Brady, Scott T.] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60612 USA. [Siegel, George J.] Loyola Univ, Chicago Stritch Sch Med, Dept Neurol & Cell Biol, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Chicago Stritch Sch Med, Dept Neurobiol, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Chicago Stritch Sch Med, Dept Anat, Maywood, IL 60153 USA. [Siegel, George J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. [Albers, R. Wayne] NINDS, Sect Enzymes, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Price, Donald] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. [Price, Donald] Johns Hopkins Univ, Sch Med, Dept Neurol, Div Neuropathol, Baltimore, MD 21205 USA. [Price, Donald] Johns Hopkins Univ, Sch Med, Dept Neurosci, Div Neuropathol, Baltimore, MD 21205 USA. [Benjamins, Joyce] Wayne State Univ, Dept Neurol, Detroit Med Ctr, Univ Hlth Ctr, Detroit, MI 48201 USA. [Fisher, Stephen] Univ Michigan, Ann Arbor, MI 48109 USA. [Fisher, Stephen] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA. [Hall, Alison] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. [Hall, Alison] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. [Bazan, Nicolas] Louisiana State Univ, Hlth Sci Ctr, Neurosci Ctr Excellence, New Orleans, LA 70112 USA. [Coyle, Joseph] Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02478 USA. RP Brady, ST (reprint author), Univ Illinois, Dept Anat & Cell Biol, 808 S Wood St,Room 578,M-C 512, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095901-6 PY 2012 BP XXI EP XXI PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BFN78 UT WOS:000320652300001 ER PT J AU Brady, ST Siegel, GJ AF Brady, Scott T. Siegel, George J. BE Brady, ST Siegel, GJ Albers, RW Price, DL TI BASIC NEUROCHEMISTRY PRINCIPLES OF MOLECULAR, CELLULAR AND MEDICAL NEUROBIOLOGY EIGHTH EDITION Preface SO BASIC NEUROCHEMISTRY: PRINCIPLES OF MOLECULAR, CELLULAR, AND MEDICAL NEUROBIOLOGY, 8THEDITION LA English DT Editorial Material; Book Chapter C1 [Brady, Scott T.] Univ Illinois, Dept Anat & Cell Biol, Chicago, IL 60612 USA. [Siegel, George J.] Loyola Univ, Chicago Stritch Sch Med, Dept Neurol & Cell Biol, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Chicago Stritch Sch Med, Dept Neurobiol, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Chicago Stritch Sch Med, Dept Anat, Maywood, IL 60153 USA. [Siegel, George J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. RP Brady, ST (reprint author), Univ Illinois, Dept Anat & Cell Biol, 808 S Wood St,Room 578,M-C 512, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095901-6 PY 2012 BP XXIII EP XXIV PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BFN78 UT WOS:000320652300002 ER PT B AU Siegel, GJ AF Siegel, George J. BE Brady, ST Siegel, GJ Albers, RW Price, DL TI SPECTRIN AND LIPID RAFT MEMBRANE COMPONENTS PARTICIPATE IN THE PATHOLOGY OF BRAIN INJURY SO BASIC NEUROCHEMISTRY: PRINCIPLES OF MOLECULAR, CELLULAR, AND MEDICAL NEUROBIOLOGY, 8THEDITION LA English DT Editorial Material; Book Chapter C1 [Siegel, George J.] Loyola Univ, Dept Neurol & Cell Biol, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Dept Neurobiol, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Dept Anat, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Siegel, George J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. RP Siegel, GJ (reprint author), Loyola Univ, Dept Neurol & Cell Biol, Chicago Stritch Sch Med, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095901-6 PY 2012 BP 37 EP 37 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BFN78 UT WOS:000320652300006 ER PT J AU Siegel, GJ AF Siegel, George J. BE Brady, ST Siegel, GJ Albers, RW Price, DL TI THERAPY OF BRAIN EDEMA: POTENTIAL PHARMACOLOGIC REGULATION OF AQUAPORIN 4 SO BASIC NEUROCHEMISTRY: PRINCIPLES OF MOLECULAR, CELLULAR, AND MEDICAL NEUROBIOLOGY, 8THEDITION LA English DT Editorial Material; Book Chapter C1 [Siegel, George J.] Loyola Univ, Dept Neurol & Cell Biol, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Dept Neurobiol, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Dept Anat, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Siegel, George J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. RP Siegel, GJ (reprint author), Loyola Univ, Dept Neurol & Cell Biol, Chicago Stritch Sch Med, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095901-6 PY 2012 BP 59 EP 60 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BFN78 UT WOS:000320652300008 ER PT J AU Siegel, GJ AF Siegel, George J. BE Brady, ST Siegel, GJ Albers, RW Price, DL TI GLYCINERGIC NEUROTRANSMISSION AND NEUROLOGIC DISEASE SO BASIC NEUROCHEMISTRY: PRINCIPLES OF MOLECULAR, CELLULAR, AND MEDICAL NEUROBIOLOGY, 8THEDITION LA English DT Editorial Material; Book Chapter ID MICE IN-VIVO; DENTATE GYRUS; BETA-SUBUNIT; RECEPTOR; HYPEREKPLEXIA; GEPHYRIN; COLLYBISTIN; MUTATIONS; SYNAPSES; EXCITABILITY C1 [Siegel, George J.] Loyola Univ, Dept Neurol & Cell Biol, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Dept Neurobiol, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Dept Anat, Chicago Stritch Sch Med, Maywood, IL 60153 USA. [Siegel, George J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. RP Siegel, GJ (reprint author), Loyola Univ, Dept Neurol & Cell Biol, Chicago Stritch Sch Med, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 37 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095901-6 PY 2012 BP 250 EP 255 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BFN78 UT WOS:000320652300022 ER PT J AU Lill, CM Tanzi, RE Bertram, L AF Lill, Christina M. Tanzi, Rudolph E. Bertram, Lars BE Brady, ST Siegel, GJ Albers, RW Price, DL TI Genetics of Neurodegenerative Diseases SO BASIC NEUROCHEMISTRY: PRINCIPLES OF MOLECULAR, CELLULAR, AND MEDICAL NEUROBIOLOGY, 8THEDITION LA English DT Article; Book Chapter ID AMYOTROPHIC-LATERAL-SCLEROSIS; GENOME-WIDE ASSOCIATION; FAMILIAL ALZHEIMERS-DISEASE; CREUTZFELDT-JAKOB-DISEASE; FRONTOTEMPORAL LOBAR DEGENERATION; GAMMA-SECRETASE ACTIVITY; ONSET PARKINSON-DISEASE; LEWY BODY DISEASE; HUNTINGTONS-DISEASE; APOLIPOPROTEIN-E C1 [Lill, Christina M.] Johannes Gutenberg Univ Mainz, Dept Neurol, D-55122 Mainz, Germany. [Tanzi, Rudolph E.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, Genet & Aging Res Unit, Boston, MA 02129 USA. [Bertram, Lars] Max Planck Inst Mol Genet, Neuropsychiat Genet Grp, Dept Vertebrate Genom, D-14195 Berlin, Germany. RP Lill, CM (reprint author), Johannes Gutenberg Univ Mainz, Dept Neurol, D-55122 Mainz, Germany. RI Lill, Christina/J-9449-2015 OI Lill, Christina/0000-0002-2805-1307 NR 96 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095901-6 PY 2012 BP 719 EP 736 PG 18 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BFN78 UT WOS:000320652300064 ER PT B AU Siegel, GJ AF Siegel, George J. BE Brady, ST Siegel, GJ Albers, RW Price, DL TI EPIGENETIC MODIFICATIONS AND NEUROLOGIC DISEASE SO BASIC NEUROCHEMISTRY: PRINCIPLES OF MOLECULAR, CELLULAR, AND MEDICAL NEUROBIOLOGY, 8THEDITION LA English DT Editorial Material; Book Chapter ID EMERGING ROLE; INHIBITORS; DISORDERS C1 [Siegel, George J.] Loyola Univ, Chicago Stritch Sch Med, Dept Neurol & Cell Biol, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Chicago Stritch Sch Med, Dept Neurobiol, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ, Chicago Stritch Sch Med, Dept Anat, Maywood, IL 60153 USA. [Siegel, George J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. RP Siegel, GJ (reprint author), Loyola Univ, Chicago Stritch Sch Med, Dept Neurol & Cell Biol, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095901-6 PY 2012 BP 731 EP 733 PG 3 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BFN78 UT WOS:000320652300065 ER PT B AU Siegel, GJ AF Siegel, George J. BE Brady, ST Siegel, GJ Albers, RW Price, DL TI INHIBITION OF TRANSGLUTAMINASE AS A POTENTIAL THERAPY IN POLYGLUTAMINE REPEAT DISEASES SO BASIC NEUROCHEMISTRY: PRINCIPLES OF MOLECULAR, CELLULAR, AND MEDICAL NEUROBIOLOGY, 8THEDITION LA English DT Editorial Material; Book Chapter ID HUNTINGTONS-DISEASE; NEURONAL DEATH C1 [Siegel, George J.] Loyola Univ Chicago, Stritch Sch Med, Dept Neurol, Maywood, IL 60153 USA. [Siegel, George J.] Loyola Univ Chicago, Stritch Sch Med, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. [Siegel, George J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Hines, IL 60141 USA. RP Siegel, GJ (reprint author), Loyola Univ Chicago, Stritch Sch Med, Dept Neurol, Maywood, IL 60153 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-095901-6 PY 2012 BP 852 EP 853 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BFN78 UT WOS:000320652300078 ER PT S AU Maier, VK Becker, PB AF Maier, Verena K. Becker, Peter B. BE Morse, RH TI A Defined In Vitro System to Study ATP-Dependent Remodeling of Short Chromatin Fibers SO CHROMATIN REMODELING: METTHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE ATP-dependent chromatin remodeling; Nucleosome sliding; Chromatin reconstitution; Nucleosomal arrays; ACF; ATPase; Linker histone; Chromatin accessibility; Nucleosome mapping ID LINKER HISTONE; ACF AB ATP-dependent remodeling factors regulate chromatin structure by catalyzing processes such as nucleosome repositioning or conformational changes of nucleosomes. Predominantly, their enzymatic properties have been investigated using mononucleosomal substrates. However, short nucleosomal arrays represent a much better mimic of the physiological chromatin context. Here, we provide a protocol for the enzyme-free reconstitution of regularly spaced nucleosomal arrays. We then explain how these arrays can serve as substrates to monitor ATP-dependent nucleosome movements and changes in the accessibility of nucleosomal DNA. C1 [Maier, Verena K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02115 USA. [Becker, Peter B.] Univ Munich, Adolf Butenandt Inst, Munich, Germany. RP Maier, VK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02115 USA. OI Becker, Peter B./0000-0001-7186-0372 NR 15 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-476-6 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2012 VL 833 BP 255 EP 270 DI 10.1007/978-1-61779-477-3_16 D2 10.1007/978-1-61779--477-3 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFY94 UT WOS:000321932900017 PM 22183599 ER PT J AU Willers, H Pfaffle, HN Zou, L AF Willers, Henning Pfaeffle, Heike N. Zou, Lee BE Kelley, MR TI Targeting Homologous Recombination Repair in Cancer SO DNA REPAIR IN CANCER THERAPY: MOLECULAR TARGETS AND CLINICAL APPLICATIONS LA English DT Article; Book Chapter ID DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; CELL LUNG-CANCER; FANCONI-ANEMIA PATHWAY; ATM-DEPENDENT PHOSPHORYLATION; MARKED CLINICAL RADIOSENSITIVITY; HISTONE H2AX PHOSPHORYLATION; HOLLIDAY JUNCTION RESOLVASE; MAINTAINS GENOMIC STABILITY; REPLICATION STRESS-RESPONSE C1 [Willers, Henning; Pfaeffle, Heike N.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Zou, Lee] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. RP Willers, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 409 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-385000-3 PY 2012 BP 119 EP 160 DI 10.1016/B978-0-12-384999-1.10007-1 PG 42 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BFT92 UT WOS:000321303900009 ER PT J AU Geyer, MB Jacobson, JS AF Geyer, Mark B. Jacobson, Judith S. BE Cairo, MS Perkins, SL TI Epidemiology of Hematological Malignancies of Children, Adolescents, and Young Adults SO HEMATOLOGICAL MALIGNANCIES IN CHILDREN, ADOLESCENTS AND YOUNG ADULTS LA English DT Article; Book Chapter ID NON-HODGKIN-LYMPHOMA; JUVENILE MYELOMONOCYTIC LEUKEMIA; PEDIATRIC MYELODYSPLASTIC SYNDROMES; ACUTE LYMPHOBLASTIC-LEUKEMIA; EPSTEIN-BARR-VIRUS; B-CELL LYMPHOMA; FANCONI-ANEMIA; UNITED-STATES; CANCER GROUP; CHILDHOOD C1 [Geyer, Mark B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Geyer, Mark B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Jacobson, Judith S.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Jacobson, Judith S.] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA. RP Geyer, MB (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. OI Geyer, Mark/0000-0001-5248-9117 NR 55 TC 1 Z9 1 U1 0 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4299-60-2 PY 2012 BP 1 EP 13 PG 13 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA BFP07 UT WOS:000320848700001 ER PT J AU Chavarro, JE Toth, TL AF Chavarro, Jorge E. Toth, Thomas L. BE Gillman, MW Poston, L TI Obesity and fertility SO MATERNAL OBESITY LA English DT Article; Book Chapter ID BODY-MASS INDEX; IN-VITRO FERTILIZATION; POLYCYSTIC-OVARY-SYNDROME; ASSISTED REPRODUCTIVE TECHNOLOGY; OVULATORY DISORDER INFERTILITY; EARLY-PREGNANCY LOSS; LIVE BIRTH-RATES; SEMEN QUALITY; LIFE-STYLE; BARIATRIC SURGERY C1 [Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Chavarro, Jorge E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Toth, Thomas L.] MGH Vitro Fertilizat Unit, Boston, MA USA. [Toth, Thomas L.] Massachusetts Gen Hosp, Reprod Endocrinol & Infertil Fellowship Training, Boston, MA 02114 USA. [Toth, Thomas L.] Harvard Univ, Sch Med, Boston, MA USA. RP Chavarro, JE (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. NR 93 TC 0 Z9 0 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-00396-5 PY 2012 BP 20 EP 33 D2 10.1017/CBO9780511782466 PG 14 WC Nutrition & Dietetics; Obstetrics & Gynecology SC Nutrition & Dietetics; Obstetrics & Gynecology GA BFS07 UT WOS:000321114100004 ER PT J AU Scremin, OU Holschneider, DP AF Scremin, Oscar U. Holschneider, Daniel P. BE Watson, C Paxinos, G Puelles, L TI Vascular Supply SO MOUSE NERVOUS SYSTEM LA English DT Article; Book Chapter ID CEREBRAL-BLOOD-FLOW; TRAUMATIC BRAIN-INJURY; CENTRAL-NERVOUS-SYSTEM; MOUSE-BRAIN; STATISTICAL-ANALYSIS; RAT-BRAIN; COMPUTED-TOMOGRAPHY; ANESTHETIZED MOUSE; HYDROGEN CLEARANCE; GLUCOSE-METABOLISM C1 [Scremin, Oscar U.] VA Greater Los Angeles Healthcare Syst, Res Dept, Los Angeles, CA USA. [Scremin, Oscar U.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Holschneider, Daniel P.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Univ So Calif, Keck Sch Med, Dept Behav Sci Neurol Cell & Neurobiol, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Viterbi Sch Engn, Dept Biomed Engn, Los Angeles, CA USA. RP Scremin, OU (reprint author), VA Greater Los Angeles Healthcare Syst, Res Dept, Los Angeles, CA USA. NR 80 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-091918-8 PY 2012 BP 459 EP 472 DI 10.1016/B978-0-12-369497-3.10014-7 PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BFP24 UT WOS:000320856100015 ER PT J AU Maes, C Kronenberg, HM AF Maes, Christa Kronenberg, Henry M. BE Glorieux, FH Pettifor, JM Juppner, H TI Postnatal Bone Growth: Growth Plate Biology, Bone Formation, and Remodeling SO PEDIATRIC BONE: BIOLOGY & DISEASES, 2ND EDITION LA English DT Article; Book Chapter ID TRANSCRIPTION FACTOR PU.1; MESENCHYMAL STEM-CELLS; HYPERTROPHIC CHONDROCYTE DIFFERENTIATION; RECEPTOR-RELATED PROTEIN-5; HYPOXIA-INDUCIBLE FACTOR; FACTOR-I GENE; NF-KAPPA-B; SKELETAL DEVELOPMENT; INDIAN-HEDGEHOG; OSTEOBLAST DIFFERENTIATION C1 [Maes, Christa] Katholieke Univ Leuven, Lab Expt Med & Endocrinol, Gasthuisberg O&N 1, Louvain, Belgium. [Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA USA. [Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Maes, C (reprint author), Katholieke Univ Leuven, Lab Expt Med & Endocrinol, Gasthuisberg O&N 1, Louvain, Belgium. NR 300 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-382041-9 PY 2012 BP 55 EP 82 DI 10.1016/B978-0-12-382040-2.10004-8 PG 28 WC Endocrinology & Metabolism; Orthopedics; Pediatrics SC Endocrinology & Metabolism; Orthopedics; Pediatrics GA BFP28 UT WOS:000320857100005 ER PT B AU Potts, JT Gardella, TJ AF Potts, John T. Gardella, Thomas J. BE Glorieux, FH Pettifor, JM Juppner, H TI Parathyroid Hormone and Calcium Homeostasis SO PEDIATRIC BONE: BIOLOGY & DISEASES, 2ND EDITION LA English DT Article; Book Chapter ID (PTH)/PTH-RELATED PEPTIDE RECEPTOR; AMINO-ACID-SEQUENCE; PROTEIN-COUPLED-RECEPTORS; PTH-RELATED PEPTIDE; MESSENGER-RIBONUCLEIC-ACID; FAMILIAL ISOLATED HYPOPARATHYROIDISM; EXTRACELLULAR CA2+-SENSING RECEPTOR; INHIBITS BONE-RESORPTION; OSTEOBLAST-LIKE CELLS; NEONATAL SEVERE HYPERPARATHYROIDISM C1 [Potts, John T.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Potts, John T.] Harvard Univ, Sch Med, Boston, MA USA. [Gardella, Thomas J.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Div Endocrinol, Boston, MA 02114 USA. RP Potts, JT (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. NR 368 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-382041-9; 978-0-12-382040-2 PY 2012 BP 109 EP 140 DI 10.1016/B978-0-12-382040-2.10006-1 PG 32 WC Endocrinology & Metabolism; Orthopedics; Pediatrics SC Endocrinology & Metabolism; Orthopedics; Pediatrics GA BFP28 UT WOS:000320857100007 ER PT B AU Bergwitz, C Juppner, H AF Bergwitz, Clemens Jueppner, Harald BE Glorieux, FH Pettifor, JM Juppner, H TI Phosphate Homeostasis Regulatory Mechanisms SO PEDIATRIC BONE: BIOLOGY & DISEASES, 2ND EDITION LA English DT Article; Book Chapter ID FIBROBLAST-GROWTH-FACTOR; FAMILIAL TUMORAL CALCINOSIS; VITAMIN-D-RECEPTOR; OSTEOBLAST-LIKE CELLS; PARATHYROID-HORMONE GENE; CHRONIC KIDNEY-DISEASE; P-I COTRANSPORTER; HEREDITARY HYPOPHOSPHATEMIC RICKETS; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; RESECTION-RELATED HYPOPHOSPHATEMIA C1 [Bergwitz, Clemens] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Bergwitz, Clemens] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Med & Pediat, Endocrine Unit, Boston, MA 02114 USA. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Med & Pediat, Pediat Nephrol Unit, Boston, MA 02114 USA. [Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 299 TC 1 Z9 1 U1 1 U2 13 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-382041-9; 978-0-12-382040-2 PY 2012 BP 141 EP 161 DI 10.1016/B978-0-12-382040-2.10007-3 PG 21 WC Endocrinology & Metabolism; Orthopedics; Pediatrics SC Endocrinology & Metabolism; Orthopedics; Pediatrics GA BFP28 UT WOS:000320857100008 ER PT J AU St-Arnaud, R Demay, MB AF St-Arnaud, Rene Demay, Marie B. BE Glorieux, FH Pettifor, JM Juppner, H TI Vitamin D Biology SO PEDIATRIC BONE: BIOLOGY & DISEASES, 2ND EDITION LA English DT Article; Book Chapter ID D-DEFICIENCY RICKETS; RECEPTOR-KNOCKOUT MICE; RETINOID-X-RECEPTOR; D-DEPENDENT RICKETS; 25-HYDROXYVITAMIN D-3-1-ALPHA-HYDROXYLASE GENE; D-3 1-ALPHA-HYDROXYLASE GENE; PARATHYROID-HORMONE GENE; MINERAL ION HOMEOSTASIS; CHICK TIBIAL FRACTURE; D-RESPONSIVE ELEMENT C1 [St-Arnaud, Rene] Shriners Hosp Children, Genet Unit, Montreal, PQ, Canada. [St-Arnaud, Rene] McGill Univ, Dept Surg, Montreal, PQ H3A 2T5, Canada. [St-Arnaud, Rene] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Demay, Marie B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. RP St-Arnaud, R (reprint author), Shriners Hosp Children, Genet Unit, Montreal, PQ, Canada. NR 281 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-382041-9 PY 2012 BP 163 EP 187 DI 10.1016/B978-0-12-382040-2.10008-5 PG 25 WC Endocrinology & Metabolism; Orthopedics; Pediatrics SC Endocrinology & Metabolism; Orthopedics; Pediatrics GA BFP28 UT WOS:000320857100009 ER PT B AU Bastepe, M Juppner, H Thakker, RV AF Bastepe, Murat Jueppner, Harald Thakker, Rajesh V. BE Glorieux, FH Pettifor, JM Juppner, H TI Parathyroid Disorders SO PEDIATRIC BONE: BIOLOGY & DISEASES, 2ND EDITION LA English DT Article; Book Chapter ID PSEUDOHYPOPARATHYROIDISM TYPE-IB; MULTIPLE ENDOCRINE NEOPLASIA; TUMOR-SUPPRESSOR GENE; PROTEIN ALPHA-SUBUNIT; ALBRIGHT HEREDITARY OSTEODYSTROPHY; PROGRESSIVE OSSEOUS HETEROPLASIA; CALCIUM-SENSING RECEPTOR; STIMULATORY G-PROTEIN; FAMILIAL ISOLATED HYPERPARATHYROIDISM; HORMONE-RELATED PEPTIDE C1 [Bastepe, Murat] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Bastepe, Murat; Jueppner, Harald] Harvard Univ, Sch Med, Boston, MA USA. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Med & Pediat, Endocrine Unit, Boston, MA USA. [Jueppner, Harald] Massachusetts Gen Hosp, Dept Med & Pediat, Pediat Nephrol Unit, Boston, MA USA. [Thakker, Rajesh V.] Churchill Hosp, OCDEM, Nuffield Dept Med, Acad Endocrine Unit, Oxford OX3 7LJ, England. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. OI Thakker, Rajesh/0000-0002-1438-3220 NR 344 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-382041-9; 978-0-12-382040-2 PY 2012 BP 557 EP 588 DI 10.1016/B978-0-12-382040-2.10021-8 PG 32 WC Endocrinology & Metabolism; Orthopedics; Pediatrics SC Endocrinology & Metabolism; Orthopedics; Pediatrics GA BFP28 UT WOS:000320857100022 ER PT B AU Mertens, R Rodriguez-Galindo, C Casanova, M AF Mertens, Rolf Rodriguez-Galindo, Carlos Casanova, Michela BE Schneider, DT Brecht, IB Olson, TA Ferrari, A TI Nasopharyngeal Carcinoma SO RARE TUMORS IN CHILDREN AND ADOLESCENTS SE Pediatric Oncology LA English DT Article; Book Chapter ID INTENSITY-MODULATED RADIOTHERAPY; BARR-VIRUS DNA; QUALITY-OF-LIFE; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; RADIATION-THERAPY IMRT; CAPSID ANTIGEN-IGA; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; JUVENILE ANGIOFIBROMAS; PEDIATRIC-ONCOLOGY C1 [Mertens, Rolf] Rhein Westfal TH Aachen, Abt Kinderheilkunde, Fak Med, D-52057 Aachen, Germany. [Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodriguez-Galindo, Carlos] Childrens Hosp, Boston, MA 02115 USA. [Casanova, Michela] Ist Nazl Tumori, Pediat Oncol Unit, I-20133 Milan, Italy. RP Mertens, R (reprint author), Rhein Westfal TH Aachen, Abt Kinderheilkunde, Fak Med, Pauwelstr 1, D-52057 Aachen, Germany. EM rmertens@ukaachen.de NR 110 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-642-04196-9 J9 PEDIATR ONCOL-BERLIN PY 2012 BP 145 EP 159 DI 10.1007/978-3-642-04197-6_17 D2 10.1007/978-3-642-04197-6 PG 15 WC Oncology; Pediatrics SC Oncology; Pediatrics GA BFR05 UT WOS:000321020700017 ER PT S AU Citi, L Barbieri, R AF Citi, Luca Barbieri, Riccardo BE Murray, A TI PhysioNet 2012 Challenge: Predicting Mortality of ICU Patients using a Cascaded SVM-GLM Paradigm SO 2012 COMPUTING IN CARDIOLOGY (CINC), VOL 39 SE Computers in Cardiology Series LA English DT Proceedings Paper CT 39th Conference on Computing in Cardiology CY SEP 09-12, 2012 CL AGH Univ Sci & Technol, Krakow, POLAND SP European Soc Cardiol, EMB, IEEE, PhysioNet, Silvermedia, Mortara, Drager, GE, Aspel, itAm, Physiol Measurement, Zoll, IBM HO AGH Univ Sci & Technol ID INTENSIVE-CARE-UNIT; HOSPITAL MORTALITY; ADMISSION; MODEL AB The focus of the PhysioNet/CinC Challenge 2012 is to develop methods for patient-specific prediction of in-hospital mortality using general descriptors recorded at the time of admission to the ICU and up to 37 time-series measurements collected during the first 48 hours after admission. We developed an algorithm that uses both general descriptors and time-series measurements to predict the in-hospital death (IHD) of ICU patients in Event 1, and to provide a probability estimate of IHD in Event 2. Both aggregated variables and general descriptors were used as features of quadratic Support Vector Machine (SVM) classifiers. Six SVMs were trained using, for each one, all the positive examples plus, in turn, one sixth of the negative examples in the training set. Finally, a Generalized Linear Model with probit link was used to predict the probability of IHD for Event 2 using the raw outputs of the six SVMs as regressors. A positive binary prediction of IHD for Event 1 was made when the probability estimate was higher than an optimized threshold. Official final results of the challenge reported that our entry achieved an Event 2 score of 17.88, which is the best score out of the total 23 submissions, and Event 1 score of 0.5345 (second best score). C1 [Citi, Luca] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Citi, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 4, Boston, MA 02114 USA. EM lciti@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833 NR 10 TC 2 Z9 2 U1 1 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0276-6574 BN 978-1-4673-2074-0 J9 COMPUT CARDIOL PY 2012 BP 257 EP 260 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications SC Cardiovascular System & Cardiology; Computer Science GA BFK65 UT WOS:000320270700065 ER PT J AU Resnik, L Bradford, DW Glynn, SM Jette, AM Hernandez, CJ Wills, S AF Resnik, Linda Bradford, Daniel W. Glynn, Shirley M. Jette, Alan M. Hernandez, Caitlin Johnson Wills, Sharon TI Issues in defining and measuring veteran community reintegration: Proceedings of the Working Group on Community Reintegration, VA Rehabilitation Outcomes Conference, Miami, Florida SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE community integration; community reintegration; disability evaluation; International Classification of Health, Disability, and Functioning; measurement; OIF/OEF; outcome assessment; role functioning; social functioning; veteran ID DEVELOPING CORE SETS; POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; MENTAL-HEALTH PROBLEMS; INTERNATIONAL CLASSIFICATION; BIPOLAR DISORDER; MEASURING PARTICIPATION; ENVIRONMENTAL-FACTORS; MULTIPLE-SCLEROSIS; PHYSICAL-THERAPY AB In January 2010, the Department of Veterans Affairs (VA) Rehabilitation Research and Development Service convened a State of the Art (SOTA) conference to advance the field of outcome measurement for rehabilitation-related studies. This article reports on the proceedings of the SOTA Working Group on Community Reintegration. We explored the use of the International Classification of Health, Disability, and Functioning as a theoretical framework for measuring community reintegration; identified key dimensions of community reintegration that could and/or should be measured; discussed challenges in measuring community reintegration; suggested steps to enhance community reintegration measurement; proposed future research that focuses on outcomes measures for community reintegration and the study of community reintegration outcomes; and made policy recommendations that would facilitate community reintegration research within the VA. C1 [Resnik, Linda] Providence Dept Vet Affairs VA Med Ctr, Providence, RI USA. [Resnik, Linda] Brown Univ, Dept Community Hlth, Publ Hlth Program, Providence, RI 02912 USA. [Bradford, Daniel W.] Durham VA Med Ctr, Psychosocial Rehabil & Recovery Ctr, Durham, NC USA. [Bradford, Daniel W.] Duke Univ Hosp, Durham, NC USA. [Glynn, Shirley M.] VA Greater Angeles Healthcare Syst, West Los Angeles Med Ctr, Los Angeles, CA USA. [Glynn, Shirley M.] Univ Calif Los Angeles Hlth Syst, Sch Med, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA USA. [Hernandez, Caitlin Johnson] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Wills, Sharon] Cent Texas Vet Hlth Care Syst, Ctr Trauma Recovery, Posttraumat Stress Disorder Clin Team, Austin Outpatient Clin, Austin, TX USA. [Wills, Sharon] Texas A&M Hlth Sci Ctr, Sch Med, Bryan, TX USA. RP Resnik, L (reprint author), Providence VA Med Ctr, 830 Chalkstone Ave, Providence, RI 02908 USA. EM Linda.Resnik@va.gov OI Jette, Alan/0000-0002-2117-9973 FU VA RRD FX This material is the result of work supported by VA RR&D. NR 63 TC 23 Z9 23 U1 2 U2 6 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 1 BP 87 EP 100 DI 10.1682/JRRD.2010.06.0107 PG 14 WC Rehabilitation SC Rehabilitation GA 149ES UT WOS:000319302400010 PM 22492341 ER PT J AU McQuaid, JR Marx, BP Rosen, MI Bufka, LF Tenhula, W Cook, H Keane, TM AF McQuaid, John R. Marx, Brian P. Rosen, Marc I. Bufka, Lynn F. Tenhula, Wendy Cook, Helene Keane, Terence M. TI Mental health assessment in rehabilitation research SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE assessment; computer-aided assessment; Department of Veterans Affairs; diagnosis; functioning; International Classification of Functioning, Disability, and Health; Inventory of Psychosocial Functioning; mental health; recovery; rehabilitation; research ID POSTTRAUMATIC-STRESS-DISORDER; INTERNATIONAL CLASSIFICATION; GLOBAL ASSESSMENT; SCREENING-TEST; SURVEY SF-36; AXIS-V; DEPRESSION; SCALE; DISABILITY; RELIABILITY AB Assessment in mental health research has evolved from focusing on symptoms and diagnosis to addressing a broad range of change, including psychosocial functioning. This is consistent with developments in the areas of psychosocial rehabilitation and the increase in recovery-oriented intervention models for mental disorders. We reviewed the status of assessment in mental health research, providing an overview of symptom and diagnostic assessment that is the cornerstone of most mental health research assessment. We then focused on measurement that can be applied across diagnostic groups and on functioning as a key mental health outcome. We reviewed the International Classification of Functioning, Disability, and Health and its implications for improvements in assessment. We provided an example of a new assessment, the Inventory of Psychosocial Functioning, which highlights key issues in the measurement of functioning. We then addressed improving research assessment, including issues of assessment in diverse populations and the need to capitalize on new data sources and new assessment technologies to advance assessment in mental health research. Finally, we reviewed and discussed areas for research and quality improvement, drawing on examples from the Department of Veterans Affairs to illustrate potential opportunities. C1 [McQuaid, John R.] San Francisco Dept Vet Affairs VA Med Ctr, San Francisco, CA USA. [McQuaid, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Marx, Brian P.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Marx, Brian P.; Keane, Terence M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Rosen, Marc I.] VA Connecticut Healthcare Syst, West Haven, CT USA. [Rosen, Marc I.] Yale Univ, Sch Med, New Haven, CT USA. [Bufka, Lynn F.] Amer Psychol Assoc, Washington, DC 20036 USA. [Tenhula, Wendy] VA Off Mental Hlth Serv, Washington, DC USA. [Cook, Helene] Texas A&M Univ, College Stn, TX USA. RP McQuaid, JR (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM john.mcquaid@va.gov FU VA Rehabilitation Research and Development (RRD) Service [F6441R]; U.S. Army Medical Research and Materiel Command [W81XWH-08-2-0028, W81XVVH-08-2-0100] FX Funding/Support: This material was based on work supported by the VA Rehabilitation Research and Development (RR&D) Service (grant F6441R to Dr. McQuaid) and U.S. Army Medical Research and Materiel Command (grants W81XWH-08-2-0028 and W81XVVH-08-2-0100 to Dr. Marx and Dr. Keane). NR 78 TC 1 Z9 1 U1 2 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 1 BP 121 EP 137 DI 10.1682/JRRD.2010.08.0143 PG 17 WC Rehabilitation SC Rehabilitation GA 149ES UT WOS:000319302400012 PM 22492343 ER PT J AU Stiers, W Carlozzi, N Cernich, A Velozo, C Pape, T Hart, T Gulliver, S Rogers, M Villarreal, E Gordon, S Gordon, W Whiteneck, G AF Stiers, William Carlozzi, Noelle Cernich, Alison Velozo, Craig Pape, Theresa Hart, Tessa Gulliver, Suzy Rogers, Margaret Villarreal, Edgar Gordon, Shalanda Gordon, Wayne Whiteneck, Gale TI Measurement of social participation outcomes in rehabilitation of veterans with traumatic brain injury SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE clinical practice; measurement; outcomes; participation; rehabilitation; research; social participation; traumatic brain injury; VA; veterans ID COMMUNITY INTEGRATION QUESTIONNAIRE; PORTLAND ADAPTABILITY INVENTORY; QUALITY-OF-LIFE; POSTCONCUSSION SYNDROME; PSYCHOMETRIC EVALUATION; SYMPTOMS; INDIVIDUALS; DISABILITY; SAMPLE; DEPRESSION AB Traumatic brain injury (TBI) is a significant concern in the veteran population, and the Department of Veteran Affairs (VA) has devoted substantial healthcare resources to the rehabilitation of veterans with TBI. Evaluating the outcomes of these rehabilitation activities requires measuring whether they meaningfully improve veterans' lives, especially with regard to community and vocational participation, which are strongly linked to perceived quality of life. In January 2010, the VA Rehabilitation Research and Development Service convened an invitational conference focused on outcome measurement in rehabilitation with a specific focus on veterans' community and vocational participation. This article reports on the working group, addressing the issues of conceptualizing and operationalizing such participation outcome measures for veterans with TBI; we discuss conceptual models of participation, review participation subdomains and their instruments of measurement, and identify current research issues and needs. Two avenues are identified for advancing participation measurement in veterans with TBI. First, we describe suggestions to facilitate the immediate implementation of participation measurement into TBI clinical practice and rehabilitation (cont) research within the VA healthcare system. Second, we describe recommendations for future VA research funding initiatives specific to improving the measurement of participatiOn in veterans with TBI. C1 [Stiers, William] Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, Baltimore, MD 21239 USA. [Carlozzi, Noelle] Kessler Fdn, Res Ctr, W Orange, NJ USA. [Carlozzi, Noelle] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Phys Med & Rehabil, Newark, NJ 07103 USA. [Cernich, Alison] Dept Vet Affairs VA Maryland Hlth Care Syst, Baltimore, MD USA. [Cernich, Alison] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Cernich, Alison] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. [Velozo, Craig] North Florida South Georgia Vet Hlth Syst, Gainesville, FL USA. [Velozo, Craig] Univ Florida, Dept Occupat Therapy, Gainesville, FL USA. [Pape, Theresa] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Pape, Theresa] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Hart, Tessa] Moss Rehabil Res Inst, Elkins Pk, PA USA. [Hart, Tessa] Einstein Healthcare Network, Dept Psychiat, Einstein Med Ctr, Philadelphia, PA USA. [Gulliver, Suzy] Cent Texas Vet Hlth Care Syst, Waco VA Med Ctr, Ctr Excellence Res Returning War Vet, Waco, TX USA. [Gulliver, Suzy] Texas A&M Hlth Sci Ctr, Coll Med, Bryan, TX USA. [Rogers, Margaret] Amer Speech Language Hearing Assoc, Rockville, MD USA. [Villarreal, Edgar] VA Eastern Colorado Hlth Care Syst, Denver, CO USA. [Gordon, Shalanda] Cent Texas Vet Hlth Care Syst, Austin Outpatient Clin, Austin, TX USA. [Gordon, Shalanda] St Phillips Coll, San Antonio, TX USA. [Gordon, Wayne] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY USA. [Whiteneck, Gale] Craig Hosp, Englewood, CO USA. RP Stiers, W (reprint author), Johns Hopkins Univ, Sch Med, Dept Phys Med & Rehabil, 5601 Loch Raven Blvd,Suite 406, Baltimore, MD 21239 USA. EM wstiers1@jhmi.edu OI Pape, Theresa/0000-0001-7738-5963; Stiers, William/0000-0002-1826-8350 FU State of the Art Conference on Outcome Measures in Rehabilitation; VA Office of Research and Development FX This material was based on work supported by the State of the Art Conference on Outcome Measures in Rehabilitation, VA Office of Research and Development. NR 76 TC 6 Z9 7 U1 5 U2 11 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 1 BP 139 EP 153 DI 10.1682/JRRD.2010.070131 PG 15 WC Rehabilitation SC Rehabilitation GA 149ES UT WOS:000319302400013 PM 22492344 ER PT J AU Ullrich, PM Spungen, AM Atkinson, D Bombardier, CH Chen, YY Erosa, NA Groer, S Ottomanelli, L Tulsky, DS AF Ullrich, Philip M. Spungen, Ann M. Atkinson, Darryn Bombardier, Charles H. Chen, Yuying Erosa, Norma A. Groer, Shirley Ottomanelli, Lisa Tulsky, David S. TI Activity and participation after spinal cord injury: State-of-the-art report SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE activity; disability; employment; functioning; measurement; outcomes; participation; quality of life; rehabilitation; spinal cord injury ID FUNCTIONAL INDEPENDENCE MEASURE; POSTACUTE REHABILITATION; WALKING INDEX; PSYCHOMETRIC PROPERTIES; AUTONOMY QUESTIONNAIRE; WHEELCHAIR PROPULSION; ENVIRONMENTAL-FACTORS; MEASURING DEPRESSION; PHYSICAL-ACTIVITY; BALANCE SCALE AB The importance of activities and community participation for persons with spinal cord injury (SCI) has been recognized for decades and yet theoretical and empirical advances have been limited. This report summarizes the recommendations for researchers on the topic of measuring activity and participation among persons with SCI formulated by the Spinal Cord Injury workgroup at the State-of-the-Art Conference on Outcome Measures in Rehabilitation held in January 2010. Activity and participation were defined as independent constructs ideally measured in reference to personal values and environmental influences. Measures of activity, participation, and factors influencing activity and participation are reviewed and critiqued. Gaps in available measures are described, measures in development are discussed, and suggestions for future research are made. C1 [Ullrich, Philip M.] Dept Vet Affairs VA Puget Sound Healthcare Syst, Spinal Cord Injury & Disorders Serv, Seattle, WA USA. [Ullrich, Philip M.; Bombardier, Charles H.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Spungen, Ann M.] James J Peters VA Med Ctr, VA Rehabil Res & Dev, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY USA. [Atkinson, Darryn] Inst Rehabil, Houston, TX USA. [Atkinson, Darryn] Res Mem Hermann, Houston, TX USA. [Chen, Yuying] Univ Alabama Birmingham, Dept Phys Med & Rehabil, Birmingham, AL USA. [Erosa, Norma A.] Texas A&M Univ, College Stn, TX USA. [Groer, Shirley; Ottomanelli, Lisa] James A Haley Vet Hosp, VA Hlth Serv Res & Dev, Ctr Excellence Maximizing Rehabil Outcomes, Tampa, FL 33612 USA. [Tulsky, David S.] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI 48109 USA. RP Ullrich, PM (reprint author), SCI D Serv, 128NAT,1660 S Columbian Way, Seattle, WA 98108 USA. EM philip.ullrich@va.gov NR 101 TC 11 Z9 12 U1 7 U2 16 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 1 BP 155 EP 173 DI 10.1682/JRRD.2010.06.0108 PG 19 WC Rehabilitation SC Rehabilitation GA 149ES UT WOS:000319302400014 PM 22492345 ER PT J AU Coates, AS Millar, EK O'Toole, SA Molloy, TJ Viale, G Goldhirsch, A Regan, MM Gelber, RD Sun, Z Castiglione-Gertsch, M Gusterson, B Musgrove, EA Sutherland, RL AF Coates, Alan S. Millar, Ewan Ka O'Toole, Sandra A. Molloy, Timothy J. Viale, Giuseppe Goldhirsch, Aron Regan, Meredith M. Gelber, Richard D. Sun, Zhuoxin Castiglione-Gertsch, Monica Gusterson, Barry Musgrove, Elizabeth A. Sutherland, Robert L. TI Prognostic interaction between expression of p53 and estrogen receptor in patients with node-negative breast cancer: results from IBCSG Trials VIII and IX SO BREAST CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; GENE-EXPRESSION; PREDICTIVE-VALUE; ADJUVANT CHEMOTHERAPY; MUTATION STATUS; TP53 MUTATIONS; THERAPY; ENDOCRINE; ALPHA; IMMUNOHISTOCHEMISTRY AB Introduction: The prognostic significance of p53 protein expression in early breast cancer remains uncertain, with some but not all studies finding an association with poorer outcomes. Estrogen receptor (ER) expression is both a positive prognostic marker and predictive of response to endocrine therapies. The relationship between these biomarkers is unknown. Methods: We constructed tissue microarrays (TMAs) from available pathological material from 1113 patients participating in two randomized clinical trials comparing endocrine therapy alone versus chemo-endocrine therapy in node-negative breast cancer. Expression of p53 defined as >10% positive nuclei was analyzed together with prior immunohistochemical assays of ER performed at central pathological review of whole tumor sections. Results: ER was present (i.e. >1% positive tumor cell nuclei) in 80.1% (880/1092). p53 expression was significantly more frequent when ER was absent, 125/212 (59%) than when ER was present, 171/880 (19%), p <0.0001. A significant qualitative interaction was observed such that p53 expression was associated with better disease-free survival (DFS) and overall survival (OS) among patients whose tumors did not express ER, but worse DFS and OS among patients whose tumors expressed ER. The interaction remained significant after allowance for pathologic variables, and treatment. Similar effects were seen when luminal and non-luminal intrinsic subtypes were compared. Conclusions: Interpretation of the prognostic significance of p53 expression requires knowledge of concurrent expression of ER. The reason for the interaction between p53 and ER is unknown but may reflect qualitatively different p53 mutations underlying the p53 expression in tumors with or without ER expression. C1 [Coates, Alan S.; Millar, Ewan Ka; O'Toole, Sandra A.; Molloy, Timothy J.; Musgrove, Elizabeth A.; Sutherland, Robert L.] Garvan Inst Med Res, Kinghorn Canc Ctr & Canc Res Program, Darlinghurst, NSW 2010, Australia. [Coates, Alan S.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Coates, Alan S.; Viale, Giuseppe; Goldhirsch, Aron; Regan, Meredith M.; Gelber, Richard D.; Sun, Zhuoxin; Castiglione-Gertsch, Monica; Gusterson, Barry; Sutherland, Robert L.] Int Breast Canc Study Grp, Bern, Switzerland. [Millar, Ewan Ka] St George Hosp, Dept Anat Pathol, South Eastern Area Lab Serv, Kogarah, NSW 2217, Australia. [Millar, Ewan Ka] Univ Western Sydney, Sch Med & Hlth Sci, Campbelltown, NSW 2560, Australia. [Millar, Ewan Ka] Univ New S Wales, Fac Med, Sch Med Sci, Kensington, NSW 2052, Australia. [O'Toole, Sandra A.; Musgrove, Elizabeth A.; Sutherland, Robert L.] Univ New S Wales, Fac Med, St Vincents Clin Sch, Kensington, NSW 2052, Australia. [O'Toole, Sandra A.] Royal Prince Alfred Hosp, Dept Tissue Pathol & Diagnost Oncol, Camperdown, NSW 2050, Australia. [O'Toole, Sandra A.] Univ Sydney, Cent Clin Sch, Sydney, NSW 2006, Australia. [Viale, Giuseppe] Div Pathol & Lab Med, Cent Pathol Off, Int Breast Canc Study Grp, I-20141 Milan, Italy. [Viale, Giuseppe] European Inst Oncol, I-20141 Milan, Italy. [Viale, Giuseppe] Univ Milan, I-20122 Milan, Italy. [Goldhirsch, Aron] European Inst Oncol, Dept Med, Div Med Oncol, I-20141 Milan, Italy. [Regan, Meredith M.; Gelber, Richard D.; Sun, Zhuoxin] Harvard Univ, Sch Med, Harvard Sch Publ Hlth Boston, IBCSG Stat Ctr,Dana Farber Canc Inst, Boston, MA 02215 USA. RP Coates, AS (reprint author), Garvan Inst Med Res, Kinghorn Canc Ctr & Canc Res Program, Darlinghurst, NSW 2010, Australia. EM alan.coates@ibcsg.org OI Millar, Ewan/0000-0002-9778-3253 FU National Health and Medical Research Council [535903, 427601]; Cancer Institute New South Wales [10/TPG/1-04, 10/CRF/1-07, 11/CDF/3-26, 11/CDF/3-25]; Cancer Institute New South Wales (Sydney Catalyst Translational Research Centre) [11/TRC/1-02]; Australia and New Zealand Breast Cancer Trials Group; Australian Cancer Research Foundation; Sydney Breast Cancer Foundation; RT Hall Trust; Petre Foundation; Swedish Society for Cancer Research; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); Swiss Cancer League; United States National Institutes of Health [CA-75362] FX The authors would like to thank Ms Joanne Scorer for assistance in preparing the manuscript. We thank the patients who participated in the clinical trials, and the contributions of the physicians, nurses, data managers, and pathologists of the International Breast Cancer Study Group. This work was supported by the National Health and Medical Research Council (Program Grant 535903 EA Musgrove, RL Sutherland; Fellowship 427601 RL Sutherland), the Cancer Institute New South Wales (Translational Program Grant 10/TPG/1-04 RL Sutherland, EA Musgrove, EKA Millar, SA O'Toole; Sydney Catalyst Translational Research Centre 11/TRC/1-02 RL Sutherland; Fellowships 10/CRF/1-07 SA O'Toole, 11/CDF/3-26 EA Musgrove, 11/CDF/3-25 TJ Molloy), the Australia and New Zealand Breast Cancer Trials Group (RL Sutherland, SA O'Toole), the Australian Cancer Research Foundation (RL Sutherland, EA Musgrove), the Sydney Breast Cancer Foundation (SA O'Toole), the RT Hall Trust (RL Sutherland) and the Petre Foundation (RL Sutherland). Additional support for IBCSG Trials VIII and IX was provided in part by the Swedish Society for Cancer Research; the Frontier Science and Technology Research Foundation; the Swiss Group for Clinical Cancer Research (SAKK); the Swiss Cancer League; and the United States National Institutes of Health (CA-75362). NR 53 TC 18 Z9 18 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 6 AR R143 DI 10.1186/bcr3348 PG 12 WC Oncology SC Oncology GA 160YO UT WOS:000320156600014 PM 23127292 ER PT J AU Holmes, MD Chen, WY AF Holmes, Michelle D. Chen, Wendy Y. TI Hiding in plain view: the potential for commonly used drugs to reduce breast cancer mortality SO BREAST CANCER RESEARCH LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIALS; RECEPTOR-NEGATIVE BREAST; PROSPECTIVE COHORT; DIABETIC-PATIENTS; POSTMENOPAUSAL WOMEN; ACE-INHIBITORS; BETA-BLOCKERS; CHINESE WOMEN; RISK AB Many medications have been developed for one purpose but then are found to have other clinical activities. There is tremendous interest in whether non-cancer medications may potentially have effects on breast cancer survival. In this review article, we have presented and evaluated the evidence for several commonly used over-the-counter and prescription medications - including aspirin (and other nonsteroidal anti-inflammatory drugs), beta-blockers, angiotensin-converting enzyme inhibitors, statins, digoxin, and metformin - that have been evaluated among breast cancer survivors in prospective studies. Substantial scientific evidence supports the hypothesis that some of these common and relatively safe drugs may reduce breast cancer mortality among those with the disease by an amount that rivals the mortality reduction gained by currently used therapies. In particular, the evidence is strongest for aspirin (approximately 50% reduction), statins (approximately 25% reduction), and metformin (approximately 50% reduction). As these drugs are generic and inexpensive, there is little incentive for the pharmaceutical industry to fund the randomized trials that would show their effectiveness definitively. We advocate that confirmation of these findings in randomized trials be considered a high research priority, as the potential impact on human lives saved could be immense. C1 [Holmes, Michelle D.; Chen, Wendy Y.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Holmes, Michelle D.; Chen, Wendy Y.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Holmes, Michelle D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Holmes, MD (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA. EM michelle.holmes@channing.harvard.edu NR 49 TC 15 Z9 15 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 6 AR 216 DI 10.1186/bcr3336 PG 9 WC Oncology SC Oncology GA 160YO UT WOS:000320156600006 PM 23227958 ER PT J AU Pogoda, TK Hendricks, AM Iverson, KM Stolzmann, KL Krengel, MH Baker, E Meterko, M Lew, HL AF Pogoda, Terri K. Hendricks, Ann M. Iverson, Katherine M. Stolzmann, Kelly L. Krengel, Maxine H. Baker, Errol Meterko, Mark Lew, Henry L. TI Multisensory impairment reported by veterans with and without mild traumatic brain injury history SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE Afghanistan; blast injuries; brain injuries; depression; hearing impairment; Iraq; multisensory impairment; nonblast injuries; posttraumatic stress disorder; vestibular impairment; veterans; vision impairment ID POSTTRAUMATIC-STRESS-DISORDER; DUAL SENSORY IMPAIRMENT; PERSISTENT POSTCONCUSSIVE SYMPTOMS; POLYTRAUMA CLINICAL TRIAD; IRAQ WAR VETERANS; ENDURING FREEDOM; EVERYDAY COMPETENCE; BLAST; PREVALENCE; HEALTH AB With the use of Veterans Health Administration and Department of Defense databases of veterans who completed a Department of Veterans Affairs comprehensive traumatic brain injury (TBI) evaluation, the objectives of this study were to (1) identify the co-occurrence of self-reported auditory, visual, and vestibular impairment, referred to as multisensory impairment (MSI), and (2) examine demographic, deployment-related, and mental health characteristics that were potentially predictive of MSI. Our sample included 13,746 veterans with either a history of deployment-related mild TBI (mTBI) (n = 9,998) or no history of TBI (n = 3,748). The percentage of MSI across the sample was 13.9%, but was 17.4% in a subsample with mTBI history that experienced both nonblast and blast injuries. The factors that were significantly predictive of reporting MSI were older age, being female, lower rank, and etiology of injury. Deployment-related mTBI history, posttraumatic stress disorder, and depression were also significantly predictive of reporting MSI, with mTBI history the most robust after adjusting for these conditions. A better comprehension of impairments incurred by deployed servicemembers is needed to fully understand the spectrum of blast and nonblast dysfunction and may allow for more targeted interventions to be developed to address these issues. C1 [Pogoda, Terri K.; Iverson, Katherine M.; Stolzmann, Kelly L.; Baker, Errol; Meterko, Mark] Dept Vet Affairs VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Pogoda, Terri K.; Hendricks, Ann M.; Meterko, Mark] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Hendricks, Ann M.] VA Boston Healthcare Syst, Hlth Care Financing & Econ, Boston, MA 02130 USA. [Iverson, Katherine M.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr Posttraumat Stress Disorder, Boston, MA 02130 USA. [Iverson, Katherine M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Krengel, Maxine H.] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Krengel, Maxine H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Lew, Henry L.] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. [Lew, Henry L.] Def & Vet Brain Injury Ctr, Richmond, VA USA. RP Pogoda, TK (reprint author), VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, 150 S Huntington Ave 152M, Boston, MA 02130 USA. EM terri.pogoda@va.gov RI Schueter, nicos/A-3625-2014; OI Krengel, Maxine/0000-0001-7632-590X FU VA Office of Research and Development, Health Services Research and Development Service [SDR 08-405] FX This article was based on work supported by the VA Office of Research and Development, Health Services Research and Development Service (grant SDR 08-405). NR 80 TC 20 Z9 20 U1 3 U2 5 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 7 BP 971 EP 983 DI 10.1682/JRRD.2011.06.0099 PG 13 WC Rehabilitation SC Rehabilitation GA 149EZ UT WOS:000319303100003 PM 23341273 ER PT J AU Saunders, GH Echt, KV AF Saunders, Gabrielle H. Echt, Katharina V. TI Blast exposure and dual sensory impairment: An evidence review and integrated rehabilitation approach SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Review DE auditory training; blast exposure; blast injury; central auditory processing disorder; dual sensory impairment; rehabilitation; traumatic brain injury; veteran; visual processing disorder; visual training ID TRAUMATIC BRAIN-INJURY; AUDITORY-VISUAL INTEGRATION; POLYTRAUMA NETWORK SITE; OLDER-ADULTS; MULTISENSORY INTEGRATION; CONSONANT RECOGNITION; PROCESSING DEFICITS; SPEECH RECOGNITION; ALZHEIMERS-DISEASE; HEARING IMPAIRMENT AB Combat exposures to blast can result in both peripheral damage to the ears and eyes and central damage to the auditory and visual processing areas in the brain. The functional effects of the latter include visual, auditory, and cognitive processing difficulties that manifest as deficits in attention, memory, and problem solving symptoms similar to those seen in individuals with visual and auditory processing disorders. Coexisting damage to the auditory and visual system is referred to as dual sensory impairment (DSI). The number of Operation Iraqi Freedom/Operation Enduring Freedom Veterans with DSI is vast; yet currently no established models or guidelines exist for assessment, rehabilitation, or service-delivery practice. In this article, we review the current state of knowledge regarding blast exposure and DSI and outline the many unknowns in this area. Further, we propose a model for clinical assessment and rehabilitation of blast-related DSI that includes development of a coordinated team-based approach to target activity limitations and participation restrictions in order to enhance reintegration, recovery, and quality of life. C1 [Saunders, Gabrielle H.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Dept Vet Affairs VA Rehabil Res & Dev Serv, Portland, OR USA. [Saunders, Gabrielle H.] Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Echt, Katharina V.] Atlanta VA Med Ctr, Rehabil Res & Dev Ctr Excellence & Geriatr Res, Educ & Clin Ctr, Decatur, GA USA. [Echt, Katharina V.] Emory Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Atlanta, GA USA. RP Saunders, GH (reprint author), Portland VA Med Ctr, VA RR&D Natl Ctr Rehabil Auditory Res NCRAR, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM gabrielle.saunders@va.gov FU VA Rehabilitation Research and Development Service [4844C, C4850C] FX This material is based on work supported by the VA Rehabilitation Research and Development Service (grants 4844C and C4850C). NR 104 TC 6 Z9 7 U1 1 U2 9 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 7 BP 1043 EP 1058 DI 10.1682/JRRD.2010.08.0157 PG 16 WC Rehabilitation SC Rehabilitation GA 149EZ UT WOS:000319303100008 PM 23341278 ER PT J AU Gallun, FJ Lewis, MS Folmer, RL Diedesch, AC Kubli, LR McDermott, DJ Walden, TC Fausti, SA Lew, HL Leek, MR AF Gallun, Frederick J. Lewis, M. Samantha Folmer, Robert L. Diedesch, Anna C. Kubli, Lina R. McDermott, Daniel J. Walden, Therese C. Fausti, Stephen A. Lew, Henry L. Leek, Marjorie R. TI Implications of blast exposure for central auditory function: A review SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE auditory dysfunction; auditory processing disorder; blast; central auditory dysfunction; central auditory processing; central auditory system; hearing loss; rehabilitation; traumatic brain injury; veteran ID TRAUMATIC BRAIN-INJURY; HEARING-LOSS; SPEECH IDENTIFICATION; PROCESSING DISORDER; SPATIAL SEPARATION; RECEPTIVE-FIELDS; GLOBAL WAR; CORTEX; REHABILITATION; DYSFUNCTION AB Auditory system functions, from peripheral sensitivity to central processing capacities, are all at risk from a blast event. Accurate encoding of auditory patterns in time, frequency, and space are required for a clear understanding of speech and accurate localization of sound sources in environments with background noise, multiple sound sources, and/or reverberation. Further work is needed to refine the battery of clinical tests sensitive to the sorts of central auditory dysfunction observed in individuals with blast exposure. Treatment options include low-gain hearing aids, remote-microphone technology, and auditory-training regimens, but clinical evidence does not yet exist for recommending one or more of these options. As this population ages, the natural aging process and other potential brain injuries (such as stroke and blunt trauma) may combine with blast-related brain changes to produce a population for which the current clinical diagnostic and treatment tools may prove inadequate. It is important to maintain an updated understanding of the scope of the issues present in this population and to continue to identify those solutions that can provide measurable improvements in the lives of Veterans who have been exposed to high-intensity blasts during the course of their military service. C1 [Gallun, Frederick J.; Lewis, M. Samantha; Folmer, Robert L.; Diedesch, Anna C.; McDermott, Daniel J.; Fausti, Stephen A.; Leek, Marjorie R.] Portland VA Med Ctr, Dept Vet Affairs VA Rehabil Res & Dev Natl Ctr Re, Portland, OR USA. [Gallun, Frederick J.; Lewis, M. Samantha; Folmer, Robert L.; Fausti, Stephen A.; Leek, Marjorie R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Kubli, Lina R.; Walden, Therese C.] WRNMMC, Audiol & Speech Ctr, Bethesda, MD USA. [Lew, Henry L.] DVBIC, Richmond, VA USA. RP Gallun, FJ (reprint author), VA RR&D Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Frederick.Gallun@va.gov RI Gallun, Frederick/G-3792-2012 OI Gallun, Frederick/0000-0002-4145-2199 FU VA RR&D Merit Review Award [01807]; VA RR&D Career Development II Awards [C4963-W, C7067-W]; VA RR&D Senior Research Career Scientist Award [C4042-L]; VA RR&D National Center for Rehabilitative Auditory Research FX This material was based on work supported by VA RR&D Merit Review Award (grant 01807: PIs Leek, Fausti), VA RR&D Career Development II Awards (grant C4963-W: PI Gallun; and grant C7067-W: PI Lewis), VA RR&D Senior Research Career Scientist Award (grant C4042-L: PI Leek), and the VA RR&D National Center for Rehabilitative Auditory Research. NR 76 TC 6 Z9 7 U1 0 U2 10 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 7 BP 1059 EP 1074 DI 10.1682/JRRD.2010.09.0166 PG 16 WC Rehabilitation SC Rehabilitation GA 149EZ UT WOS:000319303100009 PM 23341279 ER PT J AU Maguen, S Lau, KM Madden, E Seal, K AF Maguen, Shira Lau, Karen M. Madden, Erin Seal, Karen TI Relationship of screen-based symptoms for mild traumatic brain injury and mental health problems in Iraq and Afghanistan veterans: Distinct or overlapping symptoms? SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE depression; factor analysis; hypervigilance; insomnia; mental health; OIF/OEF; posttraumatic stress disorder; screen; traumatic brain injury; veteran ID POSTTRAUMATIC-STRESS-DISORDER; PERSISTENT POSTCONCUSSIVE SYMPTOMS; WAR VETERANS; CARE; CONFLICTS; VALIDITY AB This study used factor analytic techniques to differentiate distinct from overlapping screen-based symptoms of traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and depression in Iraq and Afghanistan veterans. These symptoms were derived from screen results of 1,549 veterans undergoing Department of Veterans Affairs postdeployment screening between April 2007 and January 2010. Veterans with positive TBI screens were approximately twice as likely to also screen positive for depression and PTSD (adjusted relative risks = 1.9 and 2.1, respectively). Irritability was a shared symptom between TBI and PTSD, and emotional numbing was a shared symptom between PTSD and depression. Symptoms unique to TBI included dizziness, headaches, memory problems, and light sensitivity. Four separate constructs emerged: TBI, PTSD, depression, and a fourth construct consisting of hypervigilance and sleep problems. These findings illuminate areas of overlap between TBI and common postdeployment mental health problems. Discriminating symptoms of TBI from mental health problems may facilitate diagnosis, triage to specialty care, and targeted symptom management. The emergence of a fourth factor consisting of sleep problems and hypervigilance highlights the need to attend to specific symptoms in the postdeployment screening process. C1 [Maguen, Shira; Lau, Karen M.; Madden, Erin; Seal, Karen] San Francisco Dept Vet Affairs VA Med Ctr, San Francisco, CA USA. [Maguen, Shira; Seal, Karen] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Maguen, Shira; Seal, Karen] San Francisco VA Med Ctr, Hlth Serv Res & Dev Res Enhancement Award Program, San Francisco, CA USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St 116-P, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov RI Schueter, nicos/A-3625-2014 FU Department of Defense Psychological Health and Traumatic Brain Injury Research Program; VA Health Sciences Research and Development Service Career Development Award FX This material was based on work supported by the Department of Defense Psychological Health and Traumatic Brain Injury Research Program and a VA Health Sciences Research and Development Service Career Development Award to Dr. Maguen. NR 27 TC 14 Z9 14 U1 2 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 7 BP 1115 EP 1125 DI 10.1682/JRRD.2011.02.0015 PG 11 WC Rehabilitation SC Rehabilitation GA 149EZ UT WOS:000319303100013 PM 23341283 ER PT J AU Littman, AJ Koepsell, TD Forsberg, CW Haselkorn, JK Boyko, EJ AF Littman, Alyson J. Koepsell, Thomas D. Forsberg, Christopher W. Haselkorn, Jodie K. Boyko, Edward J. TI Preventive services in veterans in relation to disability SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE cervical cancer screening; colon cancer screening; Department of Veterans Affairs; disability; prevention; preventive medicine; primary prevention; vaccination; Veterans; women's health ID PNEUMOCOCCAL VACCINATION STATUS; HEALTH INTERVIEW SURVEY; QUALITY-OF-CARE; AMBULATORY-CARE; MEDICAL-CENTERS; FEMALE VETERANS; MANAGED CARE; LOSE WEIGHT; HIGH-RISK; ADULTS AB Veterans with disabilities are at an increased risk of secondary impairments and may have difficulty accessing preventive services; accessibility may differ between Veterans who do and do not receive care at Department of Veterans Affairs (VA) facilities. We used data from the 2003 and 2004 Behavioral Risk Factor Surveillance System surveys to evaluate associations between disability and receipt of preventive services in Veterans. Veterans with a disability were more likely to have received influenza vaccinations (VA users and nonusers), pneumococcal vaccinations (VA nonusers: p < 0.001; VA users: p = 0.073), weight management counseling (VA nonusers: p < 0.001; male VA users: p < 0.001), lower gastrointestinal (GI) endoscopy (VA nonusers: 50-64 yr, p = 0.03; VA users: >= 65 yr, p = 0.085), mammography (VA users: p = 0.097), and serum cholesterol screening (VA nonusers: p < 0.001). Receipt was similar by disability status for fecal occult blood test (FOBT), lower GI endoscopy (VA users: 50-64 yr), human immunodeficiency virus testing, and cervical cancer screening. For no measure was there significantly lower receipt in those with versus without a disability, although there was marginal evidence in VA nonusers for overall colorectal cancer screening (i.e., lower GI endoscopy or FOBT: p = 0.063). Among Veterans, having a disability did not appear to be a barrier to receiving appropriate preventive care. C1 [Littman, Alyson J.; Koepsell, Thomas D.; Forsberg, Christopher W.; Boyko, Edward J.] Dept Vet Affairs VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. [Littman, Alyson J.; Koepsell, Thomas D.; Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Koepsell, Thomas D.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] VA Puget Sound Hlth Care Syst, Multiple Sclerosis Ctr Excellence West, Seattle, WA USA. RP Littman, AJ (reprint author), VA Puget Sound Med Ctr, Epidemiol Res & Informat Ctr, 1100 Olive Way,Metropolitan Pk West,Suite 1400, Seattle, WA 98101 USA. EM alyson@u.washington.edu FU VA Office of Research and Development Cooperative Studies; Rehabilitation Research and Development Programs; VA Rehabilitation Research and Development Service Career Development Award [6982] FX This material is based on work supported in part by the VA Office of Research and Development Cooperative Studies and Rehabilitation Research and Development Programs. Dr. Littman was supported by a VA Rehabilitation Research and Development Service Career Development Award (grant 6982). NR 55 TC 4 Z9 4 U1 3 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 3 BP 339 EP 350 DI 10.1682/JRRD.2010.12.0229 PG 12 WC Rehabilitation SC Rehabilitation GA 149EU UT WOS:000319302600003 PM 22773194 ER PT J AU Foecking, EM Fargo, KN Coughlin, LM Kim, JT Marzo, SJ Jones, KJ AF Foecking, Eileen M. Fargo, Keith N. Coughlin, Lisa M. Kim, James T. Marzo, Sam J. Jones, Kathryn J. TI Single session of brief electrical stimulation immediately following crush injury enhances functional recovery of rat facial nerve SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE electrical stimulation; facial nerve; facial paralysis; functional recovery; injury; motoneuron; peripheral nerve; regeneration; repair; therapy ID FEMORAL MOTONEURONS; GONADAL-STEROIDS; REGENERATION; ACCELERATION; TESTOSTERONE; EXPRESSION; FIELDS AB Peripheral nerve injuries lead to a variety of pathological conditions, including paresis or paralysis when the injury involves motor axons. We have been studying ways to enhance the regeneration of peripheral nerves using daily electrical stimulation (ES) following a facial nerve crush injury In our previous studies, ES was not initiated until 24 h after injury The current experiment tested whether ES administered immediately following the crush injury would further decrease the time for complete recovery from facial paralysis. Rats received a unilateral facial nerve crush injury and an electrode was positioned on the nerve proximal to the crush site. Animals received daily 30 min sessions of ES for 1 d (day of injury only), 2 d, 4 d, 7 d, or daily until complete functional recovery. Untreated animals received no ES. Animals were observed daily for the return of facial function. Our fmdings demonstrated that one session of ES was as effective as daily stimulation at enhancing the recovery of most functional parameters. Therefore, the use of a single 30 min session of ES as a possible treatment strategy should be studied in human patients with paralysis as a result of acute nerve injuries. C1 [Foecking, Eileen M.; Marzo, Sam J.; Jones, Kathryn J.] Loyola Univ Chicago, Stritch Sch Med, Dept Otolaryngol Head & Neck Surg, Maywood, IL USA. [Foecking, Eileen M.; Fargo, Keith N.; Coughlin, Lisa M.; Jones, Kathryn J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res & Dev Serv, Hines, IL 60141 USA. [Fargo, Keith N.] Loyola Univ Chicago, Dept Mol Pharmacol & Therapeut, Maywood, IL USA. [Kim, James T.] Loyola Univ Chicago, Neurosci Program, Maywood, IL USA. [Jones, Kathryn J.] Loyola Univ Chicago, Dept Microbiol & Immunol, Stritch Sch Med, Maywood, IL USA. RP Foecking, EM (reprint author), Edward Hines Jr VA Hosp, Res & Dev Serv, 5000 S 1st Ave,Bldg 1,Rm A241,Mail 151, Hines, IL 60141 USA. EM Eileen.Foecking@va.gov FU Research Funding Committee at Loyola University [200374]; Department of Veterans Affairs Rehabilitation Research and Development Service [CDA-2 RRD B6598W] FX This material was based on work supported by the Research Funding Committee at Loyola University (grant LU# 200374) and the Department of Veterans Affairs Rehabilitation Research and Development Service (grant CDA-2 RR&D B6598W). NR 16 TC 15 Z9 15 U1 0 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 3 BP 451 EP 458 DI 10.1682/JRRD.2011.03.0033 PG 8 WC Rehabilitation SC Rehabilitation GA 149EU UT WOS:000319302600012 PM 22773203 ER PT J AU Kang, JX AF Kang, Jing X. TI Identification of Metabolic Biomarkers for Personalized Nutrition SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Editorial Material C1 [Kang, Jing X.] Massachusetts Gen Hosp, LLMT, Boston, MA 02129 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, LLMT, 149,13th St,Room 4001, Boston, MA 02129 USA. EM kang.jing@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 3 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2012 VL 5 IS 2 BP I EP II DI 10.1159/000342702 PG 2 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 015FH UT WOS:000309431300001 ER PT J AU Zeiss, AM Batten, SV AF Zeiss, Antonette M. Batten, Sonja V. TI Treatment for PTSD: Clinical Practice Guidelines and steps toward further knowledge SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material C1 [Zeiss, Antonette M.; Batten, Sonja V.] US Dept Vet Affairs, Off Mental Hlth Serv, Cent Off, Washington, DC USA. RP Zeiss, AM (reprint author), US Dept Vet Affairs, Off Mental Hlth Serv, Cent Off, Washington, DC USA. EM Antonette.Zeiss@va.gov RI Schueter, nicos/A-3625-2014 NR 4 TC 0 Z9 0 U1 1 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 5 BP IX EP XII DI 10.1682/JRRD.2012.01.0015 PG 4 WC Rehabilitation SC Rehabilitation GA 149EW UT WOS:000319302800002 PM 23015587 ER PT J AU Bickel, CS Gregory, CM Azuero, A AF Bickel, C. Scott Gregory, Chris M. Azuero, Andres TI Matching initial torque with different stimulation parameters influences skeletal muscle fatigue SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE electrical stimulation; fatigue; frequency; NMES; pulse duration; rehabilitation; skeletal muscle; stimulation parameters; torque; voltage ID NEUROMUSCULAR ELECTRICAL-STIMULATION; FORCE-FREQUENCY-RELATIONSHIP; SPINAL-CORD-INJURY; QUADRICEPS FEMORIS; PULSE DURATION; CONTRACTIONS; DAMAGE; VOLUNTARY; MODULATION; TRAINS AB A fundamental barrier to using electrical stimulation in the clinical setting is an inability to maintain torque production secondary to muscle fatigue. Electrical stimulation parameters are manipulated to influence muscle torque production, and they may also influence fatigability during repetitive stimulation. Our purpose was to determine the response of the quadriceps femoris to three different fatigue protocols using the same initial torque obtained by altering stimulator parameter settings. Participants underwent fatigue protocols in which either pulse frequency (lowHz), pulse duration (lowPD), or voltage (lowV) was manipulated to obtain an initial torque that equaled 25% of maximum voluntary isometric contraction. Muscle soreness was reported on a visual analog scale 48 h after each fatigue test. The lowHz protocol resulted in the least fatigue (25% +/- 14%); the lowPD (50% +/- 13%) and lowV (48% +/- 14%) protocols had similar levels of fatigue. The lowHz protocol resulted in significantly less muscle soreness than the higher frequency protocols. Stimulation protocols that use a lower frequency coupled with long pulse durations and high voltages result in lesser amounts of muscle fatigue and perceived soreness. The identification of optimal stimulation patterns to maximize muscle performance will reduce the effect of muscle fatigue and potentially improve clinical efficacy. C1 [Bickel, C. Scott] Univ Alabama Birmingham, Dept Phys Therapy, Birmingham, AL 35294 USA. [Gregory, Chris M.] Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. [Gregory, Chris M.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Azuero, Andres] Univ Alabama Birmingham, Sch Nursing, Dept Community Hlth Outcomes & Syst, Birmingham, AL 35294 USA. RP Bickel, CS (reprint author), Univ Alabama Birmingham, Dept Phys Therapy, SHPB 387,1530 3rd Ave S, Birmingham, AL 35294 USA. EM bickel@uab.edu FU Rehabilitation Research and Development Service of the Department of Veterans Affairs (VA) [HD055929]; VA Career Development Award [B6341W]; Brain Rehabilitation Research Center of Excellence [F2182C]; VA Office of Research and Development; Malcom Randall VA Medical Center, Gainesville, Florida FX This material was based on work supported by the Rehabilitation Research and Development Service of the Department of Veterans Affairs (VA) (grant HD055929 to C. M. Gregory), a VA Career Development Award (grant B6341W to C. M. Gregory), and the Brain Rehabilitation Research Center of Excellence (grant F2182C). This work was partially supported by the VA Office of Research and Development and the Malcom Randall VA Medical Center, Gainesville, Florida. NR 29 TC 5 Z9 5 U1 0 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 2 BP 323 EP 331 DI 10.1682/JRRD.2011.02.0030 PG 9 WC Rehabilitation SC Rehabilitation GA 149ET UT WOS:000319302500012 PM 22773532 ER PT J AU Rodriguez, P Holowka, DW Marx, BP AF Rodriguez, Paola Holowka, Darren W. Marx, Brian P. TI Assessment of posttraumatic stress disorder-related functional impairment: A review SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Review DE clinical practice guideline; Department of Defense; Department of Veterans Affairs; education; family; functional impairment; intimate relationships; occupational functioning; posttraumatic stress disorder; social functioning ID QUALITY-OF-LIFE; COMPENSATION-SEEKING; MENTAL-HEALTH; VIETNAM VETERANS; COMBAT VETERANS; WAR VETERANS; INTIMATE-RELATIONSHIPS; SYMPTOM EXAGGERATION; PSYCHIATRIC STATUS; NATIONAL-GUARD AB In 2010, the Department of Veterans Affairs (VA) and Department of Defense (DOD) jointly published the revised VA/DOD Clinical Practice Guideline for Management of Posttraumatic Stress. The Clinical Practice Guideline (CPG) provides evidence-based recommendations for diagnosing and treating a spectrum of stress-related disorders. Included in the CPG were recommendations for assessing posttraumatic stress disorder (PTSD) and other stress disorder-related functional impairment. This article complements those CPG recommendations by providing information that may further guide clinicians in the assessment of functional impairment related to PTSD and other stress-related disorders. We briefly review some of the empirical literature on the association between PTSD and functional impairment and some of the more frequently used methods and measures for assessing functional impairment and introduce a new measure currently being developed by our group. We suggest that information obtained via patient self-report and/or clinician rating be supplemented whenever possible with collateral data from friends, family members, coworkers, or supervisors to provide a complete picture of current and premorbid functional status. Finally, we explore several important issues that we encourage clinicians to keep in mind when assessing functional impairment among Veterans and Active Duty servicemembers. C1 VA Boston Healthcare Syst, VA Natl Ctr Posttraumat Stress Disorder, Dept Vet Affairs, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Marx, BP (reprint author), VA Boston Healthcare Syst, VA Natl Ctr Posttraumat Stress Disorder, 150 S Huntington Ave,116B-4, Boston, MA 02130 USA. EM Brian.Marx@va.gov RI Schueter, nicos/A-3625-2014 FU DOD [W81XWH-08-2-0028] FX This material was based on work supported by award W81XWH-08-2-0028 from the DOD to Brian P. Marx. NR 99 TC 23 Z9 23 U1 3 U2 14 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 5 BP 649 EP 665 DI 10.1682/JRRD.2011.09.0162 PG 17 WC Rehabilitation SC Rehabilitation GA 149EW UT WOS:000319302800006 PM 23015577 ER PT J AU Chard, KM Ricksecker, EG Healy, ET Karlin, BE Resick, PA AF Chard, Kathleen M. Ricksecker, Elizabeth G. Healy, Ellen T. Karlin, Bradley E. Resick, Patricia A. TI Dissemination and experience with cognitive processing therapy SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE cognitive processing; cognitive processing therapy; dissemination; evidence-based psychotherapy; military; posttraumatic stress disorder; program evaluation; survey; trauma; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; VETERANS; VICTIMS AB Clinical practice guidelines suggest that cognitive behavioral therapies are recommended for the treatment of posttraumatic stress disorder (PTSD). One of these treatments, cognitive processing therapy (CPT), is an evidence-based treatment that has been shown to be effective at treating combat, assault, and interpersonal violence trauma in randomized controlled trials. The Department of Veterans Affairs (VA) Office of Mental Health Services has implemented an initiative to disseminate CPT as part of a broad effort to make evidence-based psychotherapies widely available throughout the VA healthcare system. This article provides an overview of CPT and reviews the efficacy and program evaluation data supporting its use in a variety of settings. In addition, we report on survey data from individuals who have participated in the VA initiative and on outcome data from patients treated by rollout-trained therapists. Our data suggest that many clinicians trained in the rollout show good adoption of the CPT model and demonstrate solid improvements in their patients' PTSD and depressive symptomotology. Finally, we offer recommendations for using CPT in clinical settings. C1 [Chard, Kathleen M.; Ricksecker, Elizabeth G.] Cincinnati Dept Vet Affairs VA Med Ctr, Cincinnati, OH USA. [Chard, Kathleen M.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Chard, Kathleen M.; Healy, Ellen T.; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Karlin, Bradley E.] VA Cent Off, Off Mental Hlth Serv, Washington, DC USA. [Resick, Patricia A.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Chard, KM (reprint author), Cincinnati VA Med Ctr, PTSD & Anxiety Disorders Clin, 1000 S Ft Thomas Ave, Ft Thomas, KY 41075 USA. EM Kathleen.Chard@va.gov RI Schueter, nicos/A-3625-2014 FU VA Office of Mental Health Services FX This material was based on work supported by the VA Office of Mental Health Services. NR 14 TC 31 Z9 31 U1 2 U2 8 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 5 BP 667 EP 678 DI 10.1682/JRRD.2011.10.0198 PG 12 WC Rehabilitation SC Rehabilitation GA 149EW UT WOS:000319302800007 PM 23015578 ER PT J AU Sloan, DM Bovin, MJ Schnurr, PP AF Sloan, Denise M. Bovin, Michelle J. Schnurr, Paula P. TI Review of group treatment for PTSD SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Review DE cognitive behavioral therapy; cognitive processing therapy; comparative effectiveness; Department of Veterans Affairs; effect size; group treatment; posttraumatic stress disorder; psychotherapy; review; trauma ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; OF-VETERANS-AFFAIRS; MULTICOMPONENT BEHAVIORAL TREATMENT; COGNITIVE-PROCESSING THERAPY; RANDOMIZED CONTROLLED-TRIAL; FOCUSED GROUP-THERAPY; MANAGEMENT THERAPY; EXPOSURE THERAPY; WOMEN AB The purpose of this article is to provide a brief review of group treatment for posttraumatic stress disorder (PTSD). This review includes a description of group-based treatments for PTSD and the available data on the efficacy of group treatment for PTSD. The literature review indicates that group treatment for PTSD is efficacious compared with no treatment. However, specific types of group treatment are not efficacious when compared with a nonspecific group treatment, such as psychoeducation or supportive counseling. Recommendations for practice and research are made in light of the available literature. C1 [Sloan, Denise M.; Bovin, Michelle J.] Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Sloan, Denise M.; Bovin, Michelle J.] Dept Vet Affairs Boston Healthcare Syst, Boston, MA USA. [Sloan, Denise M.; Bovin, Michelle J.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Schnurr, Paula P.] Natl Ctr PTSD, Execut Div, White River Jct, VT USA. [Schnurr, Paula P.] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 S Huntington Ave, Boston, MA 02130 USA. EM Denise.Sloan@va.gov RI Schueter, nicos/A-3625-2014; OI Sloan, Denise/0000-0002-0962-478X FU National Institute of Mental Health T32 grant [T32M11019836-14A2] FX This article was based on work supported in part by a National Institute of Mental Health T32 grant (grant T32M11019836-14A2). NR 49 TC 7 Z9 8 U1 6 U2 15 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 5 BP 689 EP 701 DI 10.1682/JRRD.2011.07.0123 PG 13 WC Rehabilitation SC Rehabilitation GA 149EW UT WOS:000319302800009 PM 23015580 ER PT J AU Jeffreys, M Capehart, B Friedman, MJ AF Jeffreys, Matthew Capehart, Bruce Friedman, Matthew J. TI Pharmacotherapy for posttraumatic stress disorder: Review with clinical applications SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Review DE best practices; guidelines; health services; medications; mental health; patient care; pharmacotherapy; PTSD; treatment; veterans ID OF-VETERANS-AFFAIRS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; TRAUMATIC BRAIN-INJURY; PRIMARY-CARE; DOUBLE-BLIND; ANXIETY DISORDERS; ADJUNCTIVE RISPERIDONE; DEPRESSIVE DISORDER; ALCOHOL DEPENDENCE AB Posttraumatic stress disorder (PTSD) is a prevalent psychiatric diagnosis among veterans and has high comorbidity with other medical and psychiatric conditions. This article reviews the pharmacotherapy recommendations from the 2010 revised Department of Veterans Affairs/Department of Defense Clinical Practice Guideline (CPG) for PTSD and provides practical PTSD treatment recommendations for clinicians. While evidence-based, trauma-focused psychotherapy is the preferred treatment for PTSD, pharmacotherapy is also an important treatment option. First-line pharmacotherapy agents include selective serotonin reuptake inhibitors and the selective serotonin-norepinephrine reuptake inhibitor venlafaxine. Second-line agents have less evidence for their usefulness in PTSD and carry a potentially greater side effect burden. They include nefazodone, mirtazapine, tricyclic antidepressants, and monoamine oxidase inhibitors. Prazosin is beneficial for nightmares. Benzodiazepines and antipsychotics, either as mono-therapy or used adjunctively, are not recommended in the treatment of PTSD. Treating co-occurring disorders, such as major depressive disorder, substance use disorders, and traumatic brain injury, is essential in maximizing treatment outcomes in PTSD. The CPG provides evidence-based treatment recommendations for treating PTSD with and without such co-occurring disorders. C1 [Jeffreys, Matthew] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Jeffreys, Matthew] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Capehart, Bruce] Durham Dept Vet Affairs Med Ctr VAMC, Durham, NC USA. [Capehart, Bruce] Duke Univ, Durham, NC USA. [Friedman, Matthew J.] Natl Ctr PTSD, White River Jct, VT USA. [Friedman, Matthew J.] White River Junction VAMC, White River Jct, VT USA. [Friedman, Matthew J.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. RP Jeffreys, M (reprint author), South Texas Vet Hlth Care Syst Psychiat, 5788 Eckhert Rd, San Antonio, TX 78240 USA. EM Matthew.Jeffreys@va.gov RI Schueter, nicos/A-3625-2014 NR 85 TC 23 Z9 25 U1 1 U2 17 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 5 BP 703 EP 715 DI 10.1682/JRRD.2011.09.0183 PG 13 WC Rehabilitation SC Rehabilitation GA 149EW UT WOS:000319302800010 PM 23015581 ER PT J AU Monson, CM Macdonald, A Brown-Bowers, A AF Monson, Candice M. Macdonald, Alexandra Brown-Bowers, Amy TI Couple/family therapy for posttraumatic stress disorder: Review to facilitate interpretation of VA/DOD Clinical Practice Guideline SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE caregiver burden; clinical practice guidelines; cognitive-behavioral therapy; couple/family therapy; emotionally focused couple therapy; mental health; PTSD; rehabilitation; strategic approach therapy; Veterans ID MENTAL-HEALTH PROBLEMS; COUPLES TREATMENT; PTSD TREATMENT; MALE VETERANS; FAMILY; COMBAT; SYMPTOMS; SOLDIERS; PROGRAM; LIFE AB A well-documented association exists among Veterans' posttraumatic stress disorder (PTSD) symptoms, family relationship problems, and mental health problems in partners and children of Veterans. This article reviews the recommendations regarding couple/family therapy offered in the newest version of the Department of Veterans Affairs (VA)/Department of Defense (DOD) VA/DOD Clinical Practice Guideline for Management of Post-Traumatic Stress. We then provide a heuristic for clinicians, researchers, and policy makers to consider when incorporating couple/family interventions into Veterans' mental health services. The range of research that has been conducted on couple/family therapy for Veterans with PTSD is reviewed using this heuristic, and suggestions for clinical practice are offered. C1 [Monson, Candice M.; Brown-Bowers, Amy] Ryerson Univ, Toronto, ON M5B 2K3, Canada. [Monson, Candice M.] Dept Vet Affairs VA Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Macdonald, Alexandra] VA Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. [Macdonald, Alexandra] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Monson, CM (reprint author), Ryerson Univ, Dept Psychol, 350 Victoria St, Toronto, ON M5B 2K3, Canada. EM candice.monson@psych.ryerson.ca RI Schueter, nicos/A-3625-2014 FU National Institute of Mental Health [R34 MH076813] FX This material was based on work supported in part by a grant from the National Institute of Mental Health (R34 MH076813). NR 40 TC 2 Z9 2 U1 0 U2 14 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 5 BP 717 EP 728 DI 10.1682/JRRD.2011.09.0166 PG 12 WC Rehabilitation SC Rehabilitation GA 149EW UT WOS:000319302800011 PM 23015582 ER PT J AU Taft, CT Creech, SK Kachadourian, L AF Taft, Casey T. Creech, Suzannah K. Kachadourian, Lorig TI Assessment and treatment of posttraumatic anger and aggression: A review SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Review DE aggression; agitation; anger; assessment; irritability; PTSD; trauma; treatment; veterans; violence ID STRESS-DISORDER SYMPTOMS; MALE VIETNAM VETERANS; COMBAT VETERANS; PTSD SYMPTOMATOLOGY; MARITALLY VIOLENT; DOMESTIC VIOLENCE; NONVIOLENT MEN; CRIME VICTIMS; HOSTILITY; THERAPY AB The Department of Veterans Affairs (VA) and Department of Defense's (DOD) recently published and updated Department of Veterans Affairs/Department of Defense VA/DOD Clinical Practice Guideline for Management of Post-Traumatic Stress includes irritability, severe agitation, and anger as specific symptoms that frequently co-occur with PTSD. For the first time, the guideline includes nine specific recommendations for the assessment and treatment of PTSD-related anger, irritability, and agitation. This article will review the literature on PTSD and its association with anger and aggression. We highlight explanatory models for these associations, factors that contribute to the occurrence of anger and aggression in PTSD, assessment of anger and aggression, and effective anger management interventions and strategies. C1 [Taft, Casey T.; Creech, Suzannah K.; Kachadourian, Lorig] Dept Vet Affairs VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Taft, Casey T.; Kachadourian, Lorig] Boston Univ, Sch Med, Boston, MA 02118 USA. [Creech, Suzannah K.] Providence VA Med Ctr, Providence, RI USA. [Creech, Suzannah K.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst 116B 4, 150 S Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov RI Schueter, nicos/A-3625-2014; OI Creech, Suzannah/0000-0002-6582-1673 FU National Institute of Mental Health [K08 MH7311701A2, T32MH019836] FX This material was based on work supported by the National Institute of Mental Health (grant K08 MH7311701A2 to the first author and grant T32MH019836). NR 69 TC 19 Z9 19 U1 0 U2 14 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 5 BP 777 EP 788 DI 10.1682/JRRD.2011.09.0156 PG 12 WC Rehabilitation SC Rehabilitation GA 149EW UT WOS:000319302800014 PM 23015585 ER PT J AU Raja, B Neptune, RR Kautz, SA AF Raja, Bhavana Neptune, Richard R. Kautz, Steven A. TI Quantifiable patterns of limb loading and unloading during hemiparetic gait: Relation to kinetic and kinematic parameters SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE gait; hemiparesis; knee angle; leg angle; loading magnitude; pattern; stroke; timing; unloading; vertical ground reaction forces ID WEIGHT-BEARING; STROKE PATIENTS; INDIVIDUALS; HEMIPLEGIA; ADULTS; BONE; CLASSIFICATION; STABILITY; INCREASE; FRACTURE AB Persons with poststroke hemiparesis are characterized by asymmetry in limb loading (LL) and limb unloading (LU), which has been reported in static and quasi-static tasks but has not been quantified during walking. The purpose of this study was to determine the asymmetry in magnitude and duration of LL and LU in individuals with hemiparesis and its relationship with functional walking status and specific kinematic and kinetic variables during walking. Forty-four participants with chronic hemiparesis walked at their self-selected speeds and eighteen nondisabled control subjects of similar ages walked at predetermined matched speeds while three-dimensional ground reaction forces and body-segment kinematics were recorded. Magnitude of paretic LL was reduced, while duration was increased compared with the nonparetic leg and nondisabled controls walking at matched speeds. The paretic LL and LU was significantly correlated with average leg angle, while the nonparetic leg significantly correlated with average knee angle. Three different patterns of LL and LU were identified (concave, convex, and linear). Individuals with hemiparesis make several biomechanical adjustments that minimize LL of the paretic leg. LL deviations were more pronounced with increased lateral placement of the paretic foot and with decreased functional gait speed. Characterization of these deviations may inspire new strategies for rehabilitation. C1 [Raja, Bhavana] Univ Florida, Rehabil Sci Doctoral Program, Gainesville, FL USA. [Neptune, Richard R.] Univ Texas Austin, Dept Mech Engn, Austin, TX 78712 USA. [Kautz, Steven A.] Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. [Kautz, Steven A.] Med Univ S Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Kautz, Steven A.] Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA. RP Kautz, SA (reprint author), 77 President St,MSC 700, Charleston, SC 29425 USA. EM kautz@musc.edu OI Kautz, Steven/0000-0003-3151-8235 FU National Institutes of Health [RO1 HD46820]; VA Rehabilitation Research and Development Service FX This material was based on work supported by the National Institutes of Health (grant RO1 HD46820) and the VA Rehabilitation Research and Development Service. NR 32 TC 6 Z9 6 U1 1 U2 5 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 9 BP 1293 EP 1304 DI 10.1682/JRRD.2011.02.0018 PG 12 WC Rehabilitation SC Rehabilitation GA 149FB UT WOS:000319303300002 PM 23408212 ER PT J AU Hind, J Divyak, E Zielinski, J Taylor, A Hartman, M Gangnon, R Robbins, J AF Hind, Jacqueline Divyak, Elizabeth Zielinski, Jill Taylor, Andrew Hartman, Michael Gangnon, Ronald Robbins, JoAnne TI Comparison of standardized bariums with varying rheological parameters on swallowing kinematics in males SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE aspiration; barium; deglutition; dysphagia; fluids; geriatrics; radiology; residue; swallowing; videofluoroscopy ID PENETRATION-ASPIRATION SCALE; INTERVENTIONS; MANAGEMENT; DYSPHAGIA; DEMENTIA; LIQUIDS AB This study measured dose-response of a range of commercially available liquid barium materials designed for use in videofluoroscopic oropharyngeal swallowing assessments, particularly as they relate to the necessity of adding a thickening agent for swallow safety. A group of 25 adult males representing various medical diagnoses consented to participate, with 16 qualifying to complete a videofluoroscopic swallowing assessment with liquid barium materials of three viscosities (nectar: 300 cP, thin honey: 1,500 cP, thick honey: 3,000 cP). Outcome measures included airway invasion (Penetration-Aspiration score), postswallow residue, and patient preference. Penetration-Aspiration and residue scores did not significantly differ between thin honey and thick honey bariums. Significantly more severe airway invasion was observed with nectar boluses than with two levels of honey boluses (p < 0.001). Significantly more residue was observed in the oral cavity (p < 0.002) and valleculae (p < 0.001) with thin and thick honey bariums than with nectar barium. Thin honey was rated as "easy" or "average" to drink by 67% of subjects, compared with 54% for thick honey. This study supports the use of thin honey barium over thick honey barium during videofluoroscopic swallowing assessments because the two honey bariurns were comparable in terms of airway protection and postswallow residue in the oropharynx and the thin honey was preferred by patients. C1 [Hind, Jacqueline; Divyak, Elizabeth; Zielinski, Jill; Hartman, Michael; Robbins, JoAnne] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Hind, Jacqueline; Taylor, Andrew; Hartman, Michael; Gangnon, Ronald; Robbins, JoAnne] Univ Wisconsin, Madison, WI USA. RP Hind, J (reprint author), VAMC GRECC 11G,2500 Overlook Terrace, Madison, WI 53705 USA. EM jahind@wisc.edu FU VA Veterans Health Administration; Office of Research and Development; Rehabilitation Research and Development Service [RRP 07-314]; Geriatric Research Education and Clinical Center Manuscript FX This material was based on work supported by the VA Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service (grant RRP 07-314). This is Geriatric Research Education and Clinical Center Manuscript 2011-02. NR 15 TC 8 Z9 8 U1 0 U2 5 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 9 BP 1399 EP 1404 DI 10.1682/JRRD.2011.09.0180 PG 6 WC Rehabilitation SC Rehabilitation GA 149FB UT WOS:000319303300010 PM 23408220 ER PT J AU Sawers, A Hahn, ME Kelly, VE Czerniecki, JM Kartin, D AF Sawers, Andrew Hahn, Michael E. Kelly, Valerie E. Czerniecki, Joseph M. Kartin, Deborah TI Beyond componentry: How principles of motor learning can enhance locomotor rehabilitation of individuals with lower limb loss-A review SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Review DE amputee; artificial limb; gait; learning; limb loss; locomotion; practice; prosthesis; rehabilitation; training ID TRAINING COMPLEX SKILLS; TRANS-FEMORAL AMPUTEES; EXTERNAL-FOCUS; MENTAL PRACTICE; CONTEXTUAL INTERFERENCE; DYADIC PROTOCOL; ACQUISITION; AMPUTATION; FEEDBACK; KNOWLEDGE AB Relatively little attention has been given to the use of well-established motor learning strategies to enable individuals with lower limb loss to effectively and safely learn to walk with their prostheses in the home and community. Traditionally, such outcomes have been pursued by focusing on the design and function of a patient's prosthesis, rather than on how he or she should learn to use it. The use of motor learning strategies may enhance physical rehabilitation outcomes among individuals with lower limb loss. This review explores these motor learning strategies and ways in which they can be applied to the physical rehabilitation of individuals with lower limb loss and highlights some of the challenges to their implementation, as well as unanswered research questions. C1 [Sawers, Andrew; Hahn, Michael E.; Czerniecki, Joseph M.] VA Puget Sound, Dept Vet Affairs VA, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Seattle, WA USA. [Sawers, Andrew; Kelly, Valerie E.; Czerniecki, Joseph M.; Kartin, Deborah] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Hahn, Michael E.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. RP Sawers, A (reprint author), Emory Univ, Wallace H Coulter Dept Biomed Engn, 313 Ferst Dr, Atlanta, GA 30332 USA. EM andrew.b.sawers@emory.edu OI Kelly, Valerie E./0000-0002-0099-9219 FU Center of Excellence grant from the Department of Veterans Affairs, Rehabilitation Research and Development [A4883C] FX This material was based on work supported by a Center of Excellence grant (A4883C) from the Department of Veterans Affairs, Rehabilitation Research and Development. NR 92 TC 6 Z9 7 U1 6 U2 25 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2012 VL 49 IS 10 BP 1431 EP 1441 DI 10.1682/JRRD.2011.12.0235 PG 11 WC Rehabilitation SC Rehabilitation GA 149FD UT WOS:000319303500002 PM 23516048 ER PT J AU Tecilazich, F Dinh, TL Veves, A AF Tecilazich, Francesco Dinh, Thanh L. Veves, Aristidis BE Bagchi, D Sreejayan, N TI Role of Peripheral Neuropathy in the Development of Foot Ulceration and Impaired Wound Healing in Diabetes Mellitus SO NUTRITIONAL AND THERAPEUTIC INTERVENTIONS FOR DIABETES AND METABOLIC SYNDROME LA English DT Editorial Material; Book Chapter ID PROTEIN-KINASE-C; GLYCATION END-PRODUCTS; SUBSTANCE-P; ENDOTHELIAL FUNCTION; ALDOSE REDUCTASE; POLYOL PATHWAY; COMPLICATIONS; BETA; SKIN; INHIBITION C1 [Tecilazich, Francesco; Veves, Aristidis] Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02115 USA. [Tecilazich, Francesco; Veves, Aristidis] Harvard Univ, Sch Med, Microcirculat Lab, Boston, MA USA. [Dinh, Thanh L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Podiatry, Boston, MA 02215 USA. RP Tecilazich, F (reprint author), Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02115 USA. NR 52 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-385084-3 PY 2012 BP 185 EP 194 DI 10.1016/B978-0-12-385083-6.00015-2 PG 10 WC Primary Health Care SC General & Internal Medicine GA BEX46 UT WOS:000318539200016 ER PT S AU Couig, MP AF Couig, Mary Pat BE Couig, MP Kelley, PW TI Willingness, Ability, and Intentions of Health Care Workers to Respond SO ANNUAL REVIEW OF NURSING RESEARCH: DISASTERS AND HUMANITARIAN ASSISTANCE, VOL 30, 2012 SE Annual Review of Nursing Research LA English DT Article; Book Chapter ID NURSES; EMERGENCY; PREPAREDNESS; PERCEPTIONS; INCIDENTS; STUDENTS; DUTY AB Health care workers (HCWs) are a critical component of the emergency management cycle (prevention, mitigation, preparation, response, and recovery). The potential for large numbers of injured from either a man-made or natural disaster has resulted in the development of surge capacity plans and attempts to predict how many HCWs will be available to respond. Since 1991 (with the majority of the research published in 2002 and later), researchers have been conducting studies to learn about the willingness, ability, and intentions of HCWs to respond to disasters. Potential and real barriers to disaster response are being explored as well. This chapter focuses on research authored or coauthored by nurses. Nurse-authored research is just a portion of the growing body of knowledge in this area; however, the findings are consistent with other published works. HCWs are more likely to be willing and able to respond to natural disasters and less likely to be willing and able during infectious outbreaks or incidents with potential exposure to harmful agents (biological, chemical, nuclear, or radiological). HCW concerns include safety of self and family, availability of protective equipment, medicines and vaccines, and caretaking responsibilities (children, elders, and pets). C1 US Dept Vet Affairs, Off Nursing Serv, Vet Hlth Adm, Washington, DC USA. RP Couig, MP (reprint author), US Dept Vet Affairs, Off Nursing Serv, Vet Hlth Adm, Washington, DC USA. NR 44 TC 1 Z9 1 U1 1 U2 6 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 0739-6686 BN 978-0-8261-1030-5 J9 ANNU REV NURS RES PY 2012 VL 30 BP 193 EP 208 DI 10.1891/0739-6686.30.193 PG 16 WC Nursing SC Nursing GA BEV16 UT WOS:000318254200010 PM 24894058 ER PT S AU Barth, RF Vicente, MGH Harling, OK Riley, KJ Binns, PJ Kiger, WS Kawabata, S AF Barth, Rolf F. Vicente, M. Graca H. Harling, Otto K. Riley, Kent J. Binns, Peter J. Kiger, W. S., III Kawabata, Shinji BE Chakravarti, A Fuss, M TI Boron Neutron Capture Therapy as a Treatment Modality for High-Grade Gliomas SO MALIGNANT GLIOMAS SE Radiation Medicine Rounds LA English DT Article; Book Chapter ID NEWLY-DIAGNOSED GLIOBLASTOMA; INTERNATIONAL DOSIMETRY EXCHANGE; EPIDERMAL-GROWTH-FACTOR; I CLINICAL-TRIAL; SOURCE C-BENS; BRAIN-TUMORS; NECK MALIGNANCIES; RECURRENT HEAD; AMINO-ACIDS; COMPUTATIONAL DOSIMETRY AB Boron neutron capture therapy (BNCT) is based on the nuclear capture and fission reactions that occur when nonradioactive boron-10 is irradiated with low-energy thermal neutrons to yield high linear energy transfer alpha particles vand recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas, head and neck cancer, and either primary or metastatic melanoma. Neutron sources for BNCT currently are limited to specially modified nuclear reactors and these are available in the United States, Japan, Argentina, several European countries, Taiwan, and China. Accelerators potentially also could be used to produce epithermal neutrons and these are being developed in a number of countries, including Japan, Russia, Belgium, and Argentina, but at this time none are being used for BNCT. The major challenge in the development of boron delivery agents has been the requirement for selective tumor targeting in order to achieve boron concentrations sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal tissue toxicity. Two boron drugs have been used clinically, sodium borocaptate or "BSH" (Na2B12H11SH) and a dihydroxyboryl derivative of phenylalanine referred to as boronophenylalanine or "BPA". In this chapter, we will provide an overview of other boron delivery agents that are under evaluation, neutron sources for BNCT, clinical dosimetry and treatment planning, and past and ongoing clinical studies. We will conclude with a summary of critical issues that must be addressed if BNCT is to move forward as a useful modality for the treatment of high-grade gliomas. C1 [Barth, Rolf F.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Vicente, M. Graca H.] Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA. [Harling, Otto K.] MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. [Riley, Kent J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Binns, Peter J.] Mt Auburn Hosp, Dept Radiat Oncol, Cambridge, MA USA. [Kiger, W. S., III] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA. [Kawabata, Shinji] Osaka Med Coll, Dept Neurosurg, Takatsuki, Osaka 569, Japan. RP Barth, RF (reprint author), Ohio State Univ, Dept Pathol, 165 Hamilton Hall,1645 Neil Ave, Columbus, OH 43210 USA. EM rolf.barth@osumc.edu NR 114 TC 0 Z9 0 U1 0 U2 2 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 2151-4208 BN 978-1-936287-76-5 J9 RADIAT MED ROUNDS PY 2012 VL 3 IS 2 BP 209 EP 226 DI 10.5003/2151-4208.3.2.209 PG 18 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BEV72 UT WOS:000318317300004 ER PT S AU Bhatt, AD Loeffler, JS Shih, HA AF Bhatt, Aashish D. Loeffler, Jay S. Shih, Helen A. BE Chakravarti, A Fuss, M TI The Role of Advanced Radiation Modalities in the Treatment of Gliomas SO MALIGNANT GLIOMAS SE Radiation Medicine Rounds LA English DT Article; Book Chapter DE brachytherapy; hypofractionated stereotactic radiotherapy; intensity modulated radiotherapy; malignant gliomas; particle therapy; proton therapy; radioimmunotherapy; stereotactic radiosurgery ID HIGH-GRADE GLIOMAS; RECURRENT GLIOBLASTOMA-MULTIFORME; INTENSITY-MODULATED RADIOTHERAPY; RECURSIVE PARTITIONING ANALYSIS; FRACTIONATED STEREOTACTIC RADIOTHERAPY; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; GAMMA-KNIFE RADIOSURGERY; PHASE-II TRIAL; ENDOTHELIAL GROWTH-FACTOR; MONOCLONAL-ANTIBODY 81C6 AB Malignant gliomas account for more than two-thirds of all adult primary malignant brain tumors diagnosed every year in the United States. Significant advancements have been achieved in treatment modalities of surgery, chemotherapy, and radiotherapy. However, the median survival times remain just over a year for glioblastoma and less than 5 years for anaplastic gliomas. Several different radiotherapeutic approaches have been investigated in the context of management of gliomas. In this chapter, we attempt to enumerate the role of advanced radiotherapy techniques and to summarize the pertinent clinical data. Despite the limited survival, enthusiasm to explore novel treatment strategies remains high with the ultimate goal of prolonging survival, improving the quality of patient lives, and minimizing toxicity. C1 [Bhatt, Aashish D.; Loeffler, Jay S.; Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Bhatt, Aashish D.; Loeffler, Jay S.; Shih, Helen A.] Harvard Univ, Sch Med, Boston, MA USA. RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hshih@partners.org NR 145 TC 0 Z9 0 U1 0 U2 2 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 2151-4208 BN 978-1-936287-76-5 J9 RADIAT MED ROUNDS PY 2012 VL 3 IS 2 BP 317 EP 337 DI 10.5003/2151-4208.3.2.317 PG 21 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BEV72 UT WOS:000318317300010 ER PT S AU Chan, AC Lam, EY Srinivasan, VJ AF Chan, Aaron C. Lam, Edmund Y. Srinivasan, Vivek J. GP IEEE TI Optimal Doppler Frequency Estimators for Ultrasound and Optical Coherence Tomography SO 2012 IEEE BIOMEDICAL CIRCUITS AND SYSTEMS CONFERENCE (BIOCAS): INTELLIGENT BIOMEDICAL ELECTRONICS AND SYSTEM FOR BETTER LIFE AND BETTER ENVIRONMENT SE Biomedical Circuits and Systems Conference LA English DT Proceedings Paper CT IEEE Biomedical Circuits and Systems Conference (BioCAS) CY NOV 28-30, 2012 CL Hsinchu, TAIWAN SP IEEE, CAS, EMB, Natl Chiao Tung Univ, Taiwan Engn Med Biol Assoc (TWEMBA) DE Cramer-Rao bounds; maximum likelihood estimation; frequency estimation; Doppler ultrasound; Doppler optical coherence tomography ID FLOW VELOCITY; BLOOD-FLOW AB The Kasai autocorrelation estimator is widely used in Doppler optical coherence tomography and ultrasound to determine blood velocities. However, as a non-parametric estimator, it may not be optimal. Assuming an additive white Gaussian noise (AWGN) model, we show that the Kasai estimator variance is far from the Cramer-Rao lower bound. Moreover, paradoxically, the Kasai estimator performance degrades as the acquisition rate is increased. By contrast, the additive white Gaussian noise maximum likelihood estimator (AWGN MLE) variance asymptotically approaches the Cramer-Rao lower bound, making it a better estimator at high acquisition rates. Nevertheless, the Kasai estimator outperforms the AWGN MLE under moderate levels of multiplicative decorrelation noise, and could therefore be considered more robust. These findings motivate further work in maximum likelihood estimators under conditions of both additive and multiplicative noise. C1 [Chan, Aaron C.; Lam, Edmund Y.] Univ Hong Kong, Dept Elect & Elect Engn, Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China. [Srinivasan, Vivek J.] Massachusetts Gen Hosp, Harvard Med Sch, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Chan, AC (reprint author), Univ Hong Kong, Dept Elect & Elect Engn, Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China. EM cwachan@eee.hku.hk; elam@eee.hku.hk; vjsriniv@nmr.mgh.harvard.edu FU Hong Kong Research Grants Council [10401797]; National Institutes of Health [R00NS067050, EB001954 R01]; American Heart Association [11IRG5440002]; Glaucoma Research Foundation Catalyst for a Cure FX We acknowledge support from the Hong Kong Research Grants Council (10401797), the National Institutes of Health (R00NS067050, EB001954 R01), the American Heart Association (11IRG5440002), and the Glaucoma Research Foundation Catalyst for a Cure. NR 12 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2163-4025 BN 978-1-4673-2293-5 J9 BIOMED CIRC SYST C PY 2012 BP 264 EP 267 PG 4 WC Computer Science, Information Systems; Engineering, Biomedical; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BEH21 UT WOS:000316563200081 ER PT B AU Liu, XH Laron, D Feeley, BT AF Liu, Xuhui Laron, Dominique Feeley, Brian T. BE Ma, CB Feeley, BT TI MUSCLE DEGENERATION IN ROTATOR CUFF TEARS SO BASIC PRINCIPLES AND OPERATIVE MANAGEMENT OF THE ROTATOR CUFF LA English DT Article; Book Chapter ID SKELETAL-MUSCLE; PPAR-GAMMA; KAPPA-B; SUPRASCAPULAR NERVE; ANTIFIBROSIS AGENT; SIGNALING PATHWAY; AKT/MTOR PATHWAY; TENDON RELEASE; STEM-CELLS; LONG-TERM C1 [Liu, Xuhui] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Orthoped Surg, San Francisco, CA 94143 USA. [Laron, Dominique] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Orthoped Surg, Ctr Sports Med, San Francisco, CA 94143 USA. [Feeley, Brian T.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Feeley, Brian T.] Hosp Special Surg, New York, NY 10021 USA. [Feeley, Brian T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Liu, XH (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Orthoped Surg, San Francisco, CA 94143 USA. NR 67 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-004-7 PY 2012 BP 49 EP 59 PG 11 WC Surgery SC Surgery GA BEI55 UT WOS:000316713000006 ER PT J AU Kollef, MH Chastre, J Clavel, M Restrepo, MI Michiels, B Kaniga, K Cirillo, I Kimko, H Redman, R AF Kollef, Marin H. Chastre, Jean Clavel, Marc Restrepo, Marcos I. Michiels, Bart Kaniga, Kone Cirillo, Iolanda Kimko, Holly Redman, Rebecca TI A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia SO CRITICAL CARE LA English DT Article ID CRITICALLY-ILL PATIENTS; HOSPITAL-ACQUIRED PNEUMONIA; INTENSIVE-CARE UNITS; ANTIBIOTIC-THERAPY; MULTICENTER; EXPOSURE; EFFICACY; SAFETY; PROCALCITONIN; PREVALENCE AB Introduction: The aim of this study was to compare a 7-day course of doripenem to a 10-day course of imipenem-cilastatin for ventilator-associated pneumonia (VAP) due to Gram-negative bacteria. Methods: This was a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem one gram as a four-hour infusion every eight hours with a fixed 10-day course of imipenem-cilastatin one gram as a one-hour infusion every eight hours (April 2008 through June 2011). Results: The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee that was blinded to treatment arm assignment and performed a scheduled review of data which showed signals that were close to the pre-specified stopping limits. The final analyses included 274 randomized patients. The clinical cure rate at the end of therapy (EOT) in the microbiological intent-to-treat (MITT) population was numerically lower for patients in the doripenem arm compared to the imipenem-cilastatin arm (45.6% versus 56.8%; 95% CI, -26.3% to 3.8%). Similarly, the clinical cure rate at EOT was numerically lower for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen, in the doripenem arm compared to the imipenem-cilastatin arm (41.2% versus 60.0%; 95% CI, -57.2 to 19.5). All cause 28-day mortality in the MITT group was numerically greater for patients in the doripenem arm compared to the imipenem-cilastatin arm (21.5% versus 14.8%; 95% CI, -5.0 to 18.5) and for patients with P. aeruginosa VAP (35.3% versus 0.0%; 95% CI, 12.6 to 58.0). Conclusions: Among patients with microbiologically confirmed late-onset VAP, a fixed 7-day course of doripenem was found to have non-significant higher rates of clinical failure and mortality compared to a fixed 10-day course of imipenem-cilastatin. Consideration should be given to treating patients with VAP for more than seven days to optimize clinical outcome. C1 [Kollef, Marin H.] Washington Univ, Sch Med, Div Pulm & Crit Care Med, St Louis, MO 63110 USA. [Chastre, Jean] Grp Hosp Pitie Salpetriere, Inst Cardiol, Serv Reanimat Med, F-75651 Paris 13, France. [Clavel, Marc] Ctr Hosp Limoges, F-87000 Limoges, France. [Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Crit Care Med, San Antonio, TX 78229 USA. [Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Div Pulm Crit Care Med, San Antonio, TX 78229 USA. [Michiels, Bart] Janssen Res & Dev, B-2340 Beerse, Belgium. [Kaniga, Kone; Cirillo, Iolanda; Kimko, Holly; Redman, Rebecca] Janssen Pharmaceut Res & Dev, Raritan, NJ 08869 USA. RP Kollef, MH (reprint author), Washington Univ, Sch Med, Div Pulm & Crit Care Med, 660 South Euclid Ave,Campus Box 8052, St Louis, MO 63110 USA. EM mkollef@dom.wustl.edu FU Janssen Pharmaceutical Research and Development; Barnes-Jewish Hospital Foundation; Janssen; National Heart, Lung, and Blood Institute [K23HL096054] FX This study was funded by Janssen Pharmaceutical Research and Development. Dr. Kollef's effort was supported by the Barnes-Jewish Hospital Foundation and Dr. Kollef has received consulting fees from Janssen. Dr. Restrepo's time is partially protected by Award Number K23HL096054 from the National Heart, Lung, and Blood Institute. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health." The funding agencies had no role in the preparation, review or approval of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs, nor the University of Texas Health Science Center at San Antonio. The remaining authors have no competing interests to declare. NR 33 TC 63 Z9 67 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2012 VL 16 IS 6 AR R218 DI 10.1186/cc11862 PG 17 WC Critical Care Medicine SC General & Internal Medicine GA 125UI UT WOS:000317566500004 PM 23148736 ER PT J AU Smith, CNC Quan, SD Morra, D Rossos, PG Khatibi, H Lo, V Wong, H Wu, RC AF Smith, C. N. C. Quan, S. D. Morra, D. Rossos, P. G. Khatibi, H. Lo, V. Wong, H. Wu, R. C. TI Understanding interprofessional communication: a content analysis of email communications between doctors and nurses SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Hospital communication system; email; content analysis; interprofessional communication ID E-MAIL COMMUNICATION; PROVIDERS; CARE; SMARTPHONES; HOSPITALS; PHYSICIAN; TEXT AB Background: Clinical communication is recognized as a major source of errors in hospitals. The lack of documentation of communication, especially among verbal interactions, often creates hindrances and impedes improvement efforts. By providing smartphones to residents and encouraging nurses to communicate with residents by email shifted much of the communication to emails which permitted analysis of content. Objective: Description on the interprofessional email communication between doctors and nurses occurring on the general internal medicine wards at two academic hospitals. Design: A prospective analysis of email communications between doctors and nurses. Setting: 34 out of the 67 residents who were on the general medicine clinical teaching units consented to allow analysis of their emails over a 6 month period. Main measures: Statistical tabulations were performed on the volume and frequency of communications as well the response time of messages. Two physicians coded the content of randomly selected emails for urgency, emotion, language, type of interaction, and subject content. Key results: A total of 13,717 emails were available for analysis. Among the emails from nurses, 39.1% were requests for a call back, 18.9% were requests for a response by email and the remaining 42.0% indicated no response was required from physicians. For the messages requesting a response by email, only 50% received an email response. Email responses had a median response time of 2.3 minutes. Content analysis revealed that messages were predominantly non-urgent. The two most frequent purposes for communications were to convey information (91%) and to request action by the physician (36%). Conclusions: A smartphone-based email system facilitated the description and content analysis of a large amount of email communication between physicians and nurses. Our findings provide a picture of the communication between physicians, nurses and other healthcare professionals. This work may help inform the further development of information and communications technology that can improve clinical communication. C1 [Smith, C. N. C.; Quan, S. D.; Morra, D.; Rossos, P. G.; Khatibi, H.; Lo, V.; Wong, H.; Wu, R. C.] Univ Hlth Network, Ctr Innovat Complex Care, Toronto, ON M5G 2C4, Canada. [Morra, D.; Wu, R. C.] Univ Hlth Network, Div Gen Internal Med, Toronto, ON M5G 2C4, Canada. [Morra, D.; Rossos, P. G.; Wu, R. C.] Univ Hlth Network, Dept Med, Toronto, ON M5G 2C4, Canada. [Wong, H.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Wong, H.] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. [Wong, H.] Harvard Univ, Sch Med, Boston, MA USA. RP Wu, RC (reprint author), Toronto Gen Hosp, 200 Elizabeth St,14EN222, Toronto, ON M5G 2C4, Canada. EM Robert.wu@uhn.ca OI Wong, Hannah/0000-0002-9740-0312 FU Ontario Ministry of Health Alternate Funding Proposal Innovation Grant FX Funding from this research was provided by the Ontario Ministry of Health Alternate Funding Proposal Innovation Grant. NR 24 TC 9 Z9 9 U1 3 U2 18 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2012 VL 3 IS 1 BP 38 EP 51 DI 10.4338/ACI-2011-11-RA-0067 PG 14 WC Medical Informatics SC Medical Informatics GA 120PG UT WOS:000317182500004 PM 23616899 ER PT J AU Laxmisan, A McCoy, AB Wright, A Sittig, DF AF Laxmisan, A. McCoy, A. B. Wright, A. Sittig, D. F. TI Clinical Summarization Capabilities of Commercially-available and Internally-developed Electronic Health Records SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Electronic health records; clinical summarization; user interface ID CARE; INFORMATION; TIME; CONSEQUENCES; PHYSICIANS; HANDOFFS; ADOPTION; SUPPORT AB Objective: Clinical summarization, the process by which relevant patient information is electronically summarized and presented at the point of care, is of increasing importance given the increasing volume of clinical data in electronic health record systems (EHRs). There is a paucity of research on electronic clinical summarization, including the capabilities of currently available EHR systems. Methods: We compared different aspects of general clinical summary screens used in twelve different EHR systems using a previously described conceptual model: AORTIS (Aggregation, Organization, Reduction, Interpretation and Synthesis). Results: We found a wide variation in the EHRs' summarization capabilities: all systems were capable of simple aggregation and organization of limited clinical content, but only one demonstrated an ability to synthesize information from the data. Conclusion: Improvement of the clinical summary screen functionality for currently available EHRs is necessary. Further research should identify strategies and methods for creating easy to use, well-designed clinical summary screens that aggregate, organize and reduce all pertinent patient information as well as provide clinical interpretations and synthesis as required. C1 [Laxmisan, A.] Baylor Coll Med, Houston VA Hlth Serv Res & Dev Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Laxmisan, A.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [McCoy, A. B.; Sittig, D. F.] Univ Texas Hlth Sci Ctr Houston UTHlth, Sch Biomed Informat, Houston, TX USA. [Wright, A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Laxmisan, A (reprint author), Baylor Coll Med Med, 2002 Holcombe Blvd, Houston, TX 77005 USA. EM archana.laxmisan@gmail.com RI McCoy, Allison/I-1951-2013 OI McCoy, Allison/0000-0003-2292-9147 FU Office of the National Coordinator for Health Information Technology [10510592] FX We thank Toby Samo, Chief Medical Officer at Allscripts for permission to use a screenshot of their summary screen. The authors would like to acknowledge Adolph Trudeau, Laura Fochtmann, Dario Giuse, Jacob McCoy, David Beck and others who provided information about the studied EHR systems and screens. This project was supported in part by Grant No. 10510592 for Patient-Centered Cognitive Support under the Strategic Health IT Advanced Research Projects Program (SHARP) from the Office of the National Coordinator for Health Information Technology. NR 39 TC 9 Z9 9 U1 1 U2 4 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2012 VL 3 IS 1 BP 80 EP 93 DI 10.4338/ACI-2011-11-RA-0066 PG 14 WC Medical Informatics SC Medical Informatics GA 120PG UT WOS:000317182500007 PM 22468161 ER PT J AU Atassi, N Schoenfeld, D Cudkowicz, M AF Atassi, Nazem Schoenfeld, David Cudkowicz, Merit BE Ravina, B Cummings, J McDermott, MP Poole, RM TI Amyotrophic lateral sclerosis SO CLINICAL TRIALS IN NEUROLOGY: DESIGN, CONDUCT, ANALYSIS LA English DT Article; Book Chapter ID HAND-HELD DYNAMOMETRY; ALS CLINICAL-TRIALS; NATURAL-HISTORY; RANDOMIZED-TRIAL; RATING-SCALE; EL-ESCORIAL; SURVIVAL; THERAPY; DISEASE; DESIGN C1 [Atassi, Nazem; Schoenfeld, David; Cudkowicz, Merit] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Atassi, Nazem; Schoenfeld, David; Cudkowicz, Merit] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Atassi, N (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. NR 50 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-76259-5 PY 2012 BP 273 EP 283 D2 10.1017/CBO9781139032445 PG 11 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA BDY84 UT WOS:000315680000025 ER PT S AU Tomblyn, MB Winkfield, KM Dabaja, BS AF Tomblyn, Michael B. Winkfield, Karen M. Dabaja, Bouthaina S. BE Tomblyn, MB Winkfield, KM Dabaja, BS TI Radiation Medicine Rounds VOLUME 3, ISSUE 3 Hematologic Malignancies Preface SO HEMATOLOGIC MALIGNANCIES SE Radiation Medicine Rounds LA English DT Editorial Material; Book Chapter C1 [Winkfield, Karen M.] Massachusetts Gen Hosp, Ctr Canc, Hematol Malignancy Serv, Dept Radiat Oncol, Boston, MA USA. [Dabaja, Bouthaina S.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 2151-4208 BN 978-1-936287-77-2 J9 RADIAT MED ROUNDS PY 2012 VL 3 IS 3 BP IX EP IX PG 1 WC Oncology; Hematology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Hematology; Radiology, Nuclear Medicine & Medical Imaging GA BEA10 UT WOS:000315828400001 ER PT S AU Barnes, J Winkfield, KM AF Barnes, Jeffrey Winkfield, Karen M. BE Tomblyn, MB Winkfield, KM Dabaja, BS TI Follicular Lymphoma SO HEMATOLOGIC MALIGNANCIES SE Radiation Medicine Rounds LA English DT Article; Book Chapter DE follicular lymphoma; radioimmunotherapy; rituximab; bendamustine; RCHOP ID NON-HODGKINS-LYMPHOMA; TERM-FOLLOW-UP; RANDOMIZED CONTROLLED-TRIAL; B-CELL LYMPHOMA; HIGH PROLIFERATION INDEX; LOW-GRADE; RITUXIMAB MAINTENANCE; STAGE-I; TREATMENT POLICY; NATURAL-HISTORY AB Follicular lymphoma is the most common type of indolent non-Hodgkin lymphoma seen in the United States. It frequently presents as asymptomatic adenopathy. Lymph node biopsy shows effacement of the lymph node architecture by closely packed follicles harboring the translocation t(14:18), bringing the immunoglobulin heavy chain regulatory region on chromosome 14 in proximity to the antiapoptotic gene BCL2 on chromosome 18. Patients with limited-stage disease, defined as involvement of nodes limited to one side of the diaphragm, are candidates for curative radiation therapy. Patients with advanced stage disease may be observed until symptomatic progression, at which time a variety of treatment options are available including monoclonal antibodies, chemoimmunotherapy, radioimmunotherapy, and stem cell transplantation. C1 [Barnes, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA. [Winkfield, Karen M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Hematol Malignancy Serv, Boston, MA 02114 USA. RP Barnes, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM jabarnes@partners.org NR 48 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 2151-4208 BN 978-1-936287-77-2 J9 RADIAT MED ROUNDS PY 2012 VL 3 IS 3 BP 393 EP 405 DI 10.5003/2151-4208.3.3.393 PG 13 WC Oncology; Hematology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Hematology; Radiology, Nuclear Medicine & Medical Imaging GA BEA10 UT WOS:000315828400004 ER PT S AU Mitin, T Winkfield, KM AF Mitin, Timur Winkfield, Karen M. BE Tomblyn, MB Winkfield, KM Dabaja, BS TI Natural Killer Cell Lymphomas SO HEMATOLOGIC MALIGNANCIES SE Radiation Medicine Rounds LA English DT Article; Book Chapter DE natural killer cell lymphoma; Epstein-Barr virus; radiation therapy; chemotherapy; salvage ID EPSTEIN-BARR-VIRUS; NON-HODGKINS-LYMPHOMA; INTERNATIONAL PROGNOSTIC INDEX; UPPER AERODIGESTIVE TRACT; NASAL-TYPE; T-CELL; ANGIOCENTRIC LYMPHOMA; (NK)/T-CELL LYMPHOMA; AGGRESSIVE NEOPLASM; RADIATION TREATMENT AB Natural killer (NK) cell lymphomas are rare malignancies. They are almost exclusively Epstein-Barr virus (EBV) driven and disproportionally affect Asian and South American populations. The World Health Organization classification divides NK cell lymphomas into two subtypes: the extranodal NK/T-cell lymphoma, nasal type, and the aggressive NK cell leukemia. From the standpoint of prognosis and treatment algorithm, NK cell lymphomas can be divided into three categories: nasal, non-nasal, and aggressive NK leukemia. This review focuses on pathobiology, diagnosis, and staging and prognosis of NK cell lymphomas and then analyzes the evidence behind current treatment modalities for nasal NK cell lymphoma. Radiation therapy techniques, doses, and concurrent systemic agents are discussed in depth. Finally, salvage strategies are also reviewed for patients who fail the initial course of aggressive multi-modality therapy. C1 [Mitin, Timur] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Boston, MA 02114 USA. [Winkfield, Karen M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Hematol Malignancy Serv, Boston, MA 02114 USA. RP Winkfield, KM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM kwinkfield@partners.org NR 78 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 2151-4208 BN 978-1-936287-77-2 J9 RADIAT MED ROUNDS PY 2012 VL 3 IS 3 BP 437 EP 450 DI 10.5003/2151-4208.3.3.437 PG 14 WC Oncology; Hematology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Hematology; Radiology, Nuclear Medicine & Medical Imaging GA BEA10 UT WOS:000315828400007 ER PT S AU Yee, AJ Winkfield, KM Raje, NS AF Yee, Andrew J. Winkfield, Karen M. Raje, Noopur S. BE Tomblyn, MB Winkfield, KM Dabaja, BS TI Plasma Cell Dyscrasias SO HEMATOLOGIC MALIGNANCIES SE Radiation Medicine Rounds LA English DT Article; Book Chapter DE multiple myeloma; monoclonal gammopathy of unknown significance; plasma cell dyscrasia ID DIAGNOSED MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE MGUS; BONE-MARROW-TRANSPLANTATION; RANDOMIZED CONTROLLED-TRIAL; PHASE-III APEX; MONOCLONAL GAMMOPATHY; SOLITARY PLASMACYTOMA; ZOLEDRONIC ACID; WORKING GROUP; LONG-TERM AB Plasma cell dyscrasias are characterized by a neoplastic proliferation of plasma cells. Multiple myeloma is the archetypal plasma cell disorder; monoclonal gammopathy of unknown significance is a precursor condition to multiple myeloma. Multiple myeloma is the second most common hematologic malignancy with a median age at diagnosis of 66. The last 2 decades have witnessed dramatic advances in the treatment of myeloma with the introduction of autologous stem cell transplant, proteasome inhibition, and immunomodulatory agents. The incorporation of novel agents in myeloma treatment has led to significant improvements in overall survival. C1 [Yee, Andrew J.; Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Multiple Myeloma, Dept Hematol Oncol, Boston, MA USA. [Winkfield, Karen M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Ctr Canc, Hematol Malignancy Serv, Boston, MA 02114 USA. RP Yee, AJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, 275 Cambridge St, Boston, MA 02114 USA. EM ayee1@partners.org NR 128 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 2151-4208 BN 978-1-936287-77-2 J9 RADIAT MED ROUNDS PY 2012 VL 3 IS 3 BP 473 EP 488 DI 10.5003/2151-4208.3.3.473 PG 16 WC Oncology; Hematology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Hematology; Radiology, Nuclear Medicine & Medical Imaging GA BEA10 UT WOS:000315828400010 ER PT S AU Abramson, JS Muse, VV AF Abramson, Jeremy S. Muse, Victorine V. BE Tomblyn, MB Winkfield, KM Dabaja, BS TI Role of FDG-PET Scans in Management of Lymphoma SO HEMATOLOGIC MALIGNANCIES SE Radiation Medicine Rounds LA English DT Article; Book Chapter DE PET; FDG; Hodgkin lymphoma; diffuse large B-cell lymphoma; non-Hodgkin lymphoma; response; staging ID POSITRON-EMISSION-TOMOGRAPHY; B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; INVOLVED-FIELD RADIOTHERAPY; COOPERATIVE-ONCOLOGY-GROUP; BONE-MARROW INVOLVEMENT; CONTRAST-ENHANCED CT; MALIGNANT-LYMPHOMA; F-18 FLUORODEOXYGLUCOSE; COMPUTED-TOMOGRAPHY AB FDG-PET scanning has emerged as a vital tool in the initial staging, interim restaging, and end of treatment response assessment in lymphoma. Compared to CT scans alone, PET evaluation at diagnosis of diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL) increases the sensitivity for disease detection, particularly in extranodal sites of disease, and will upstage patients in approximately 15% of cases. At interim restaging during chemotherapy, PET scans have proven an important prognostic tool in the setting of HL, where a negative interim PET scan predicts for a high cure rate compared to patients with persistent increased FDG activity. Interim PET scans in DLBCL, however, appear less reproducibly predictive of prognosis due to increased false positives when the scan is performed shortly after chemoimmunotherapy. At the end of treatment, PET scans enhance the ability to determine complete remission, especially in the setting of residual masses, which often represents benign sclerosis, and have thus been incorporated into standard response criteria for DLBCL and HL. Beyond achievement of complete remission, PET scans have no role currently in the long-term follow up of patients where CT scans alone appear sufficient. While having a critical role in staging and restaging of high-grade B-cell lymphomas and HL, there is presently no clearly defined role in the evaluation of low-grade histologies such as follicular lymphoma, small lymphocytic lymphoma, or marginal zone lymphoma. Active areas of investigation include using interim PET scans to guide intensification or deintensification of therapy, as well as incorporation of PET imaging into the design of radiation treatment fields. C1 [Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA. [Muse, Victorine V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Abramson, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St, Boston, MA 02114 USA. EM jabramson@partners.org NR 89 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA SN 2151-4208 BN 978-1-936287-77-2 J9 RADIAT MED ROUNDS PY 2012 VL 3 IS 3 BP 489 EP 502 DI 10.5003/2151-4208.3.3.489 PG 14 WC Oncology; Hematology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Hematology; Radiology, Nuclear Medicine & Medical Imaging GA BEA10 UT WOS:000315828400011 ER PT J AU Alam, HB AF Alam, Hasan B. TI Looking for a win-win solution Editorial on "Acute care surgery in the USA - The orthopaedic conflict" SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Alam, HB (reprint author), Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Massachusetts Gen Hosp, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 J9 INT J SURG JI Int. J. Surg. PY 2012 VL 10 IS 9 BP 409 EP 409 DI 10.1016/j.ijsu.2012.07.001 PG 1 WC Surgery SC Surgery GA 117EL UT WOS:000316935700002 PM 22796665 ER PT J AU Liu, Q Yu, FY Tang, W Su, SC Song, EW AF Liu, Qiang Yu, Feng-Yan Tang, Wei Su, Shi-Cheng Song, Er-Wei BE Liu, XY Pestka, S Shi, YF TI Cancer Stem Cell SO RECENT ADVANCES IN CANCER RESEARCH AND THERAPY SE Elsevier Insights LA English DT Article; Book Chapter ID ACUTE MYELOID-LEUKEMIA; CIRCULATING TUMOR-CELLS; BONE MORPHOGENETIC PROTEINS; ACUTE MYELOGENOUS LEUKEMIA; METASTATIC BREAST-CANCER; EPITHELIAL-MESENCHYMAL TRANSITIONS; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; SELF-RENEWAL; INITIATING CELLS C1 [Liu, Qiang; Yu, Feng-Yan; Tang, Wei; Su, Shi-Cheng; Song, Er-Wei] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Breast Surg, Guangzhou 510120, Peoples R China. [Liu, Qiang] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Song, EW (reprint author), Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Breast Surg, 107 Yanjiang West Rd, Guangzhou 510120, Peoples R China. EM songerwei02@yahoo.com.cn NR 154 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-397836-3 J9 ELSEV INSIGHT PY 2012 BP 173 EP 196 DI 10.1016/B978-0-12-397833-2.00008-X PG 24 WC Oncology SC Oncology GA BEG20 UT WOS:000316457900009 ER PT J AU Nierenberg, AA AF Nierenberg, Andrew A. BE Parker, G TI Bipolar II Disorder Modelling, Measuring and Managing Second Edition Management commentary SO BIPOLAR II DISORDER: MODELLING, MEASURING AND MANAGING, 2ND EDITION LA English DT Editorial Material; Book Chapter C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-107-60089-8 PY 2012 BP 245 EP 246 D2 10.1017/CBO9781139003315 PG 2 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BDZ04 UT WOS:000315688800028 ER PT J AU Zukotynski, KA Kim, CK AF Zukotynski, Katherine A. Kim, Chun K. BE Gerbaudo, VH TI Sarcoma SO CASE-BASED APPROACH TO PET/CT IN ONCOLOGY LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; SOFT-TISSUE SARCOMAS; GASTROINTESTINAL STROMAL TUMORS; NERVE SHEATH TUMORS; PRIMARY BONE-TUMORS; PLEUROPULMONARY SYNOVIAL SARCOMA; NEOADJUVANT THERAPY RESPONSE; FDG-PET; F-18 FLUORODEOXYGLUCOSE; OSTEOGENIC-SARCOMA C1 [Zukotynski, Katherine A.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Zukotynski, Katherine A.; Kim, Chun K.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Chun K.] Brigham & Womens Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. RP Zukotynski, KA (reprint author), Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. NR 80 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-11683-1 PY 2012 BP 466 EP 486 D2 10.1017/CBO9781139026543 PG 21 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA BDY68 UT WOS:000315670400019 ER PT S AU Thibert, R Hyland, K Chiles, J Steinberg, S Eichler, F AF Thibert, Ronald Hyland, Keith Chiles, Joe Steinberg, Steven Eichler, Florian GP SSIEM TI Levodopa Response Reveals Sepiapterin Reductase Deficiency in a Female Heterozygote with Adrenoleukodystrophy SO JIMD REPORTS - CASE AND RESEARCH REPORTS, 2011/3 SE JIMD Reports LA English DT Article; Book Chapter ID INACTIVATION; DISORDER AB We report a 4-year-old girl heterozygous for X-linked adrenoleukodystrophy (ALD) who displayed dopa-responsive motor symptoms and was subsequently diagnosed with sepiapterin reductase deficiency (SPR; OMIM 182125). Her father and paternal uncle had known ALD, and she was found to have elevated plasma very long chain fatty acids and a mutation in the ABCD1 gene. She had language delay, severe hypotonia and abnormal eye movements and responded dramatically to a trial of levodopa (4 mg/kg per day). Two mutations within the gene for sepiapterin reductase were found and cultured skin fibroblasts demonstrated near zero activity of the enzyme. This case illustrates the importance of treatment trials that may give rise to biochemical clues to the underlying diagnosis, and the need to continue to search for diagnoses despite a misleading family history. C1 [Thibert, Ronald; Eichler, Florian] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hyland, Keith; Chiles, Joe] Med Neurogenet, Atlanta, GA USA. [Steinberg, Steven] Kennedy Krieger Inst Johns Hopkins, Baltimore, MD USA. RP Eichler, F (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,ACC 708, Boston, MA 02114 USA. EM rthibert@partners.org; khyland@mnglab.com; jchiles@mnglab.com; steinbergs@kennedykrieger.org; feichler@partners.org FU NINDS NIH HHS [K08 NS052550] NR 10 TC 2 Z9 3 U1 1 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2192-8304 BN 978-3-642-24936-5 J9 JIMD REP PY 2012 VL 3 BP 79 EP 82 DI 10.1007/8904_2011_65 D2 10.1007/978-3-642-24936-5 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA BEB08 UT WOS:000315963200012 PM 23430877 ER PT J AU Demers, M Wagner, DD AF Demers, Melanie Wagner, Denisa D. TI Targeting platelet function to improve drug delivery SO ONCOIMMUNOLOGY LA English DT Editorial Material DE platelets; vascular permeability; bleeding; inflammation; tumor; thrombocytopenia ID CANCER-IMMUNOTHERAPY; INFLAMMATION; HEMORRHAGE AB Thrombocytopenia-induced tumor hemorrhage improves drug delivery to tumors. This phenomenon presents a new way to increase drug efficacy with minimal side effects. Combining anti-platelet treatment with therapeutic drugs may help us in the search for more effective ways to fight cancer. C1 [Demers, Melanie; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pediat,Childrens Hosp Boston, Immune Dis Inst,Program Cellular & Mol Med, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Dept Pediat,Childrens Hosp Boston, Immune Dis Inst,Program Cellular & Mol Med, Boston, MA 02115 USA. EM wagner@idi.harvard.edu FU National Heart, Lung and Blood Institute of the National Institutes of Health [P01 HL056949, R01 HL041002]; Terry Fox Foundation through the Canadian Cancer Society FX This work was supported by National Heart, Lung and Blood Institute of the National Institutes of Health grants P01 HL056949 and R01 HL041002 (to D.D.W.), and the Terry Fox Foundation through the Canadian Cancer Society (to M.D.). NR 9 TC 5 Z9 5 U1 2 U2 10 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 J9 ONCOIMMUNOLOGY JI OncoImmunology PD JAN-FEB PY 2012 VL 1 IS 1 BP 100 EP 102 DI 10.4161/onci.1.1.17962 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 107YR UT WOS:000316257500021 PM 22720224 ER PT J AU Ahlfors, SP Hamalainen, MS AF Ahlfors, Seppo P. Haemaelaeinen, Matti S. BE Brette, R Destexhe, A TI MEG and EEG: source estimation SO HANDBOOK OF NEURAL ACTIVITY MEASUREMENT LA English DT Article; Book Chapter ID SYNTHETIC-APERTURE MAGNETOMETRY; DIPOLE LOCALIZATION ACCURACY; BIOMAGNETIC INVERSE PROBLEM; EVOKED MAGNETIC-FIELDS; TO-NOISE-RATIOS; HUMAN-BRAIN; ELECTRICAL-ACTIVITY; CORTICAL ACTIVITY; SIMULTANEOUS MAGNETOENCEPHALOGRAPHY; ELECTROMAGNETIC TOMOGRAPHY C1 [Ahlfors, Seppo P.; Haemaelaeinen, Matti S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Ahlfors, Seppo P.; Haemaelaeinen, Matti S.] Harvard Mit Div Hlth Sci & Technol, Charlestown, MA USA. RP Ahlfors, SP (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. RI Ahlfors, Seppo/P-3644-2016 NR 143 TC 1 Z9 1 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-51622-8 PY 2012 BP 257 EP 286 D2 10.1017/CBO9780511979958 PG 30 WC Neurosciences SC Neurosciences & Neurology GA BDX02 UT WOS:000315515400007 ER PT J AU Petersen, KH Linden, H Dale, AM Einevoll, GT Stieglitz, T Brette, R Destexhe, A Bedard, C De Munck, JC Wolters, CH Clerc, M Ahlfors, SP Hamalainen, MS Frostig, RD Chen-Bee, CH Chemla, S Chavane, F Helmchen, F Bartels, A Goense, J Logothetis, N AF Petersen, K. H. Linden, H. Dale, A. M. Einevoll, G. T. Stieglitz, T. Brette, R. Destexhe, A. Bedard, C. De Munck, J. C. Wolters, C. H. Clerc, M. Ahlfors, S. P. Haemaelaeinen, M. S. Frostig, R. D. Chen-Bee, C. H. Chemla, S. Chavane, F. Helmchen, F. Bartels, A. Goense, J. Logothetis, N. BE Brette, R Destexhe, A TI HANDBOOK OF NEURAL ACTIVITY MEASUREMENT Perspectives SO HANDBOOK OF NEURAL ACTIVITY MEASUREMENT LA English DT Editorial Material; Book Chapter ID IN-VIVO; BRAIN; RECORDINGS C1 [Petersen, K. H.; Linden, H.; Einevoll, G. T.] Norwegian Univ Life Sci, Dept Math Sci & Technol, As, Norway. [Dale, A. M.] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Dale, A. M.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Einevoll, G. T.] Norwegian Univ Life Sci, Ctr Integrat Genet CIGENE, As, Norway. [Stieglitz, T.] Univ Freiburg, Lab Biomed Microtechnol, Dept Microsyst Engn IMTEK, Fac Engn, D-79106 Freiburg, Germany. [Stieglitz, T.] Univ Freiburg, Bernstein Ctr Freiburg, D-79106 Freiburg, Germany. [Brette, R.] Ecole Normale Super, Dept Cognit Sci, F-75231 Paris, France. [Destexhe, A.; Bedard, C.] CNRS, UNIC, Gif Sur Yvette, France. [De Munck, J. C.] Vrije Univ Amsterdam Med Ctr, Dept Phys & Med Technol, Amsterdam, Netherlands. [Wolters, C. H.] Univ Munster, Inst Biomagnetism & Biosignal Anal, D-48149 Munster, Germany. [Clerc, M.] INRIA Sophia Antipolis Mediterranee, Sophia Antipolis, France. [Ahlfors, S. P.; Haemaelaeinen, M. S.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA. [Ahlfors, S. P.; Haemaelaeinen, M. S.] Harvard Mit Div Hlth Sci & Technol, Charlestown, MA USA. [Frostig, R. D.; Chen-Bee, C. H.] Univ Calif Irvine, Dept Neurobiol & Behav, Dept Biomed Engn, Irvine, CA USA. [Frostig, R. D.; Chen-Bee, C. H.] Univ Calif Irvine, Ctr Neurobiol Learning & Memory, Irvine, CA 92717 USA. [Chemla, S.] Univ Lethbridge, Canadian Ctr Behav Neurosci, Lethbridge, AB T1K 3M4, Canada. [Chavane, F.] Aix Marseille Univ, CNRS, Inst Neurosci Cognit Mediterranee, Marseille, France. [Helmchen, F.] Univ Zurich, Brain Res Inst, Zurich, Switzerland. [Bartels, A.; Goense, J.; Logothetis, N.] Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72076 Tubingen, Germany. RP Petersen, KH (reprint author), Norwegian Univ Life Sci, Dept Math Sci & Technol, As, Norway. RI Stieglitz, Thomas/C-7916-2013 OI Stieglitz, Thomas/0000-0002-7349-4254 NR 26 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-51622-8 PY 2012 BP 470 EP 479 D2 10.1017/CBO9780511979958 PG 10 WC Neurosciences SC Neurosciences & Neurology GA BDX02 UT WOS:000315515400012 ER PT J AU Williams, BR Bailey, FA Woodby, LL Wittich, AR Burgio, KL AF Williams, Beverly Rosa Bailey, F. Amos Woodby, Lesa L. Wittich, Angelina R. Burgio, Kathryn L. TI "A ROOM FULL OF CHAIRS AROUND HIS BED": BEING PRESENT AT THE DEATH OF A LOVED ONE IN VETERANS AFFAIRS MEDICAL CENTERS SO OMEGA-JOURNAL OF DEATH AND DYING LA English DT Article ID INTENSIVE-CARE-UNIT; OF-LIFE CARE; FAMILY-MEMBERS; HOSPITALIZED-PATIENTS; DYING PATIENTS; END; QUALITY; PATIENT; PERSPECTIVES; PERCEPTIONS AB Historically, death took place at home where family held vigil around the dying patient. Today, family presence is an important feature of death and dying in hospital settings. We used hermeneutic phenomenology to explore experiences of being present at the hospital death of a loved one. We conducted in-depth, face-to-face interviews with 78 recently bereaved next-of-kin of veterans who died in 6 Veterans Affairs (VA) Medical Centers in the Southeast United States. Two major themes emerged: 1) "settling in," characteristic of the experiences of wives and daughters in the initial phase of the patient's hospitalization; and 2) "gathering around," characteristic of the experiences of a wider array of family members as the patient neared death. An in-depth understanding of experiences of next-of-kin present at the hospital death of a loved one can increase staff awareness of family's needs and empower staff to develop policies and procedures for supporting family members. C1 [Williams, Beverly Rosa; Bailey, F. Amos; Woodby, Lesa L.; Wittich, Angelina R.; Burgio, Kathryn L.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Williams, Beverly Rosa; Bailey, F. Amos; Woodby, Lesa L.; Burgio, Kathryn L.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. RP Williams, BR (reprint author), Univ Alabama Birmingham, CH19 218K,1720 2nd Ave South, Birmingham, AL 35294 USA. EM BWilliams@aging.uab.edu NR 98 TC 2 Z9 2 U1 1 U2 2 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0030-2228 J9 OMEGA-J DEATH DYING JI Omega-J. Death Dying PY 2012 VL 66 IS 3 BP 231 EP 263 DI 10.2190/OM.66.3.c PG 33 WC Psychology, Multidisciplinary; Social Sciences, Biomedical SC Psychology; Biomedical Social Sciences GA 099WM UT WOS:000315654500003 PM 23617101 ER PT S AU Gather, MC Yun, SH AF Gather, Malte C. Yun, Seok Hyun GP IEEE TI Lasing From Living Biological Cells Expressing Green Fluorescent Protein SO 2012 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 06-11, 2012 CL San Jose, CA ID PHOTONIC CRYSTAL LASER AB We show that GFP, a biologically produced material, is a viable optical gain medium and construct true bio-lasers, in which the optical gain is provided by living mammalian or bacterial cells synthesizing GFP. C1 [Gather, Malte C.] Tech Univ Dresden, Inst Angew Photophys, Dresden, Germany. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Med Sch, Dept Dermatol, Boston, MA 02114 USA. RP Gather, MC (reprint author), Tech Univ Dresden, Inst Angew Photophys, Dresden, Germany. EM malte.gather@iapp.de NR 10 TC 0 Z9 0 U1 2 U2 9 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-933-6 J9 CONF LASER ELECTR PY 2012 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BCK05 UT WOS:000310362401165 ER PT S AU Nizamoglu, S Gather, MC Yun, SH AF Nizamoglu, Sedat Gather, Malte C. Yun, Seok Hyun GP IEEE TI Vitamin microdroplet laser SO 2012 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 06-11, 2012 CL San Jose, CA ID SINGLE AB Stimulated emission from biomolecules enables a new class of biolasers for unconventional approaches in biomedical applications. We demonstrate vitamin microdroplet laser using riboflavin 5'-monophosphate sodium salt hydrate (a form of vitamin B2). C1 [Nizamoglu, Sedat] Harvard Sch Med, 65 Landsdowne St,UP-5, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. RP Nizamoglu, S (reprint author), Harvard Sch Med, 65 Landsdowne St,UP-5, Cambridge, MA 02139 USA. EM Nizamoglu.Sedat@mgh.harvard.edu NR 6 TC 0 Z9 0 U1 1 U2 7 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-933-6 J9 CONF LASER ELECTR PY 2012 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BCK05 UT WOS:000310362401166 ER PT J AU Billue, KL Safford, MM Salanitro, AH Houston, TK Curry, W Kim, Y Allison, JJ Estrada, CA AF Billue, Katherine L. Safford, Monika M. Salanitro, Amanda H. Houston, Thomas K. Curry, William Kim, Yongin Allison, Jeroan J. Estrada, Carlos A. TI Medication intensification in diabetes in rural primary care: a cluster-randomised effectiveness trial SO BMJ OPEN LA English DT Article ID RE-AIM FRAMEWORK; ACHIEVABLE BENCHMARKS; QUALITY IMPROVEMENT; PHYSICIAN FEEDBACK; CLINICAL INERTIA; INTERVENTION; PATIENT; MANAGEMENT; BENEFICIARIES; HYPERTENSION AB Objective: To determine the effectiveness of a provider-based intervention to improve medication intensification among patients with diabetes. Design: Effectiveness cluster-randomised trial. Baseline and follow-up cross-sections of diabetes physicians' patients. Setting: Eleven U.S. Southeastern states, 2006-2008. Participants: 205 Rural primary care physicians, 95 completed the study. Intervention: Multicomponent interactive intervention including web-based continuing medical education (CME), performance feedback and quality improvement tools. Primary outcome measures: Medication intensification, a dose increase of an existing medication or the addition of a new class of medication for glucose, blood pressure and lipids control on any of the three most recent office visits. Results: Of 364 physicians attempting to register, 102 were randomised to the intervention and 103 to the control arms; 95 physicians (intervention, n=48; control, n=47) provided data on their 1182 of their patients at baseline (intervention, n=715; control, n=467) and 945 patients at follow-up (intervention, n=479; control, n=466). For A1c control, medication intensification increased in both groups (intervention, pre 26.4% vs post 32.6%, p=0.022; control, pre 24.8% vs post 31.1%, p=0.033) (intervention, adjusted OR (AOR) 1.37; 95% CI 1.06 to 1.76; control, AOR 1.41 (95% CI 1.06 to 1.89)); however, we observed no incremental benefit solely due to the intervention (group-by-time interaction, p=0.948). Among patients with the worst glucose control (A1c >9%), intensification increased in both groups (intervention, pre 34.8% vs post 62.5%, p=0.002; control, pre 35.7% vs post 61.4%, p=0.008). Conclusions: A wide-reach, low-intensity, web-based interactive multicomponent intervention had no significant incremental effect on medication intensification for control of glucose, blood pressure or lipids for patients with diabetes of physicians practising in the rural Southeastern USA. Trial registration: NCT00403091. C1 [Billue, Katherine L.; Safford, Monika M.; Curry, William; Kim, Yongin; Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham, AL USA. [Salanitro, Amanda H.] VA Tennessee Valley Healthcare Geriatr Res Educ C, Nashville, TN USA. [Salanitro, Amanda H.] Vanderbilt Univ, Nashville, TN USA. [Houston, Thomas K.] Bedford Vet Affairs Med Ctr, Beford, MA USA. [Houston, Thomas K.; Allison, Jeroan J.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Curry, William; Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Birmingham, MA USA. [Estrada, Carlos A.] Birmingham VAMC, Vet Affairs Natl Qual Scholars Program, Birmingham, MA USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, Birmingham, AL USA. EM cestrada@uab.edu RI Houston, Thomas/F-2469-2013; OI Allison, Jeroan/0000-0003-4472-2112 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [5R18DK065001]; Veterans Affairs National Quality Scholars Program FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 5R18DK065001 to JJA. AHS and CAE were supported by the Veterans Affairs National Quality Scholars Program. The sponsors had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. NR 36 TC 2 Z9 2 U1 2 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2012 VL 2 IS 5 AR e000959 DI 10.1136/bmjopen-2012-000959 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 091MN UT WOS:000315053900014 ER PT J AU Castro, VM Gallagher, PJ Clements, CC Murphy, SN Gainer, VS Fava, M Weilburg, JB Churchil, SE Kohane, IS Iosifescu, DV Smoller, JW Perlis, RH AF Castro, Victor M. Gallagher, Patience J. Clements, Caitlin C. Murphy, Shawn N. Gainer, Vivian S. Fava, Maurizio Weilburg, Jeffrey B. Churchil, Susanne E. Kohane, Isaac S. Iosifescu, Dan V. Smoller, Jordan W. Perlis, Roy H. TI Incident user cohort study of risk for gastrointestinal bleed and stroke in individuals with major depressive disorder treated with antidepressants SO BMJ OPEN LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; POPULATION-BASED COHORT; SELECTIVE SEROTONIN; HEMORRHAGIC STROKE; TRANSPORTER; HEALTH; ESCITALOPRAM; BINDING; ENTERPRISE; CITALOPRAM AB Objective: To examine the association between exposure to newer antidepressants and risk of gastrointestinal (GI) and other bleeding complications among individuals with major depressive disorder (MDD). Design: This study uses an incident user cohort design to compare associations between incidence of vascular/bleeding events and the relative affinity (low, moderate or high) of the antidepressant for the serotonin transporter during an exposure risk period for each patient. Setting: New England healthcare system electronic medical record database. Participants: 36 389 individuals with a diagnosis of MDD and monotherapy with a selective serotonin reuptake inhibitor, serotonin-norepinephrine reuptake inhibitor or other new-generation antidepressant were identified from among 3.1 million patients in a New England healthcare system. Primary and secondary outcome measures: Rates of bleeding or other vascular complications, including acute liver failure, acute renal failure, asthma, breast cancer and hip fractures. Results: 601 GI bleeds were observed in the 21 462 subjects in the high-affinity group versus 333 among the 14 927 subjects in the lower affinity group (adjusted RR: 1.17, 95% CI 1.02 to 1.34). Similarly, 776 strokes were observed in the high-affinity group versus 434 in the lower affinity treatment group (adjusted RR: 1.18, 95% CI 1.06 to 1.32). No significant association with risk for a priori negative control outcomes, including acute liver failure, acute renal failure, asthma, breast cancer and hip fractures, was identified. Conclusions: Use of antidepressants with high affinity for the serotonin transporter may confer modestly elevated risk for GI and other bleeding complications. While multiple methodologic limitations must be considered, these results suggest that antidepressants with lower serotonin receptor affinity may be preferred in patients at greater risk for such complications. C1 [Castro, Victor M.; Gainer, Vivian S.] Partners HealthCare Syst, Partners Res Comp, Boston, MA USA. [Gallagher, Patience J.; Clements, Caitlin C.; Smoller, Jordan W.; Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Clements, Caitlin C.; Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fava, Maurizio; Weilburg, Jeffrey B.; Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin, Boston, MA 02114 USA. [Fava, Maurizio; Weilburg, Jeffrey B.; Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Res Program, Boston, MA 02114 USA. [Churchil, Susanne E.] Partners HealthCare Syst, Informat Syst, Boston, MA USA. [Kohane, Isaac S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Iosifescu, Dan V.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. i2b2 Natl Ctr Biomed Comp, Boston, MA USA. Mt Sinai Sch Med, Mood & Anxiety Disorders Program, New York, NY USA. MGH Psychiat Ctr Expt Drugs & Diagnost, Boston, MA USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. EM rperlis@partners.org FU NIH/National Library of Medicine [2U54LM008748]; National Institute of Mental Health [R01MH086026] FX The project described was supported by Award # 2U54LM008748 from the NIH/National Library of Medicine (to IK) and R01MH086026 from the National Institute of Mental Health (to RP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Library of Medicine or the National Institutes of Health. NR 53 TC 21 Z9 21 U1 1 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2012 VL 2 IS 2 AR e000544 DI 10.1136/bmjopen-2011-000544 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 091IF UT WOS:000315042100026 PM 22466034 ER PT J AU Myint, PK Kwok, CS Majumdar, SR Eurich, DT Clark, AB Espana, PP Man, SY Huang, DT Yealy, DM Angus, DC Capelastegui, A Rainer, TH Marrie, TJ Fine, MJ Loke, YK AF Myint, Phyo Kyaw Kwok, Chun Shing Majumdar, Sumit R. Eurich, Dean T. Clark, Allan B. Espana, Pedro P. Man, Shin Yan Huang, David T. Yealy, Donald M. Angus, Derek C. Capelastegui, Alberto Rainer, Timothy H. Marrie, Thomas J. Fine, Michael J. Loke, Yoon K. TI The International Community-Acquired Pneumonia (CAP) Collaboration Cohort (ICCC) study: rationale, design and description of study cohorts and patients SO BMJ OPEN LA English DT Article ID SEVERITY ASSESSMENT; PREDICTION RULE; VALIDATION; CURB-65; TOOL; METAANALYSIS; POPULATION; INFECTIONS; GUIDELINES; MANAGEMENT AB Objective: To improve the understanding of the determinants of prognosis and accurate risk stratification in community-acquired pneumonia (CAP). Design: Multicentre collaboration of prospective cohorts. Setting: 6 cohorts from the USA, Canada, Hong Kong and Spain. Participants: From a published meta-analysis of risk stratification studies in CAP, the authors identified and pooled individual patient-level data from six prospective cohort studies of CAP (three from the USA, one each from Canada, Hong Kong and Spain) to create the International CAP Collaboration Cohort. Initial essential inclusion criteria of meta-analysis were (1) prospective design, (2) in English language, (3) reported 30-day mortality and transfer to an intensive or high dependency care and (4) minimum 1000 participants. Common baseline patient characteristics included demographics, history and physical examination findings, comorbidities and laboratory and radiographic findings. Primary and secondary outcome measures: This paper reports the rationale, hypotheses and analytical framework and also describes study cohorts and patients. The authors aim to (1) compare the prognostic accuracy of existing CAP risk stratification tools, (2) assess patient-level determinants of prognosis, (3) improve risk stratification by combined use of scoring systems and (4) understand prognostic factors for specific patient groups. Results: The six cohorts assembled from 1991 to 2007 included 13 784 patients (median age 71 years, 54% men). Aside from one randomised controlled study, the remaining five were cohort studies, but all had similar inclusion criteria. Overall, there was 0%-6% missing data. A total of 6159 (44%) had severe pneumonia by Pneumonia Severity Index class IV/V. Mortality at 30 days was 8% (1036). Admission to intensive care or high dependency unit was also 8% (1059). Conclusions: International CAP Collaboration Cohort provides a pooled multicentre data set of patients with CAP, which will help us to better understand the prognosis of CAP. C1 [Myint, Phyo Kyaw; Kwok, Chun Shing; Clark, Allan B.; Loke, Yoon K.] Univ E Anglia, Norwich Med Sch, Dept Med, Norwich NR4 7TJ, Norfolk, England. [Majumdar, Sumit R.] Univ Alberta, Dept Med, Fac Med & Dent, Edmonton, AB, Canada. [Eurich, Dean T.] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada. [Espana, Pedro P.; Capelastegui, Alberto] Hosp Galdakao, Serv Neumol, Galdakao, Bizkaia, Spain. [Man, Shin Yan; Rainer, Timothy H.] Chinese Univ Hong Kong, Prince Wales Hosp, Accid & Emergency Med Acad Unit, Shatin, Hong Kong, Peoples R China. [Huang, David T.; Angus, Derek C.] Univ Pittsburgh, Sch Med, Dept Emergency Med, Pittsburgh, PA USA. [Huang, David T.; Angus, Derek C.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Ctr, Pittsburgh, PA USA. [Yealy, Donald M.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Yealy, Donald M.] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Marrie, Thomas J.] Dalhouse Univ, Halifax, NS, Canada. RP Myint, PK (reprint author), Univ E Anglia, Norwich Med Sch, Dept Med, Norwich NR4 7TJ, Norfolk, England. EM phyo.k.myint@uea.ac.uk RI Angus, Derek/E-9671-2012; Rainer, Timothy/I-2591-2013; OI Rainer, Timothy/0000-0003-3355-3237; Kwok, Chun Shing/0000-0001-7047-1586 FU Alberta Heritage Foundation; Alberta Innovates-Health Solutions; Canadian Institutes of Health Research FX None of the authors declare any conflict of interest except two authors, SRM: receives salary support awards from the Alberta Heritage Foundation and Alberta Innovates-Health Solutions (Health Scholar) and DTH: receives salary support awards from the Alberta Heritage Foundation and Canadian Institutes of Health Research. NR 40 TC 2 Z9 3 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2012 VL 2 IS 3 AR e001030 DI 10.1136/bmjopen-2012-001030 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 091JF UT WOS:000315044800069 ER PT J AU Roetker, NS Yonker, JA Lee, C Chang, V Basson, JJ Roan, CL Hauser, TS Hauser, RM Atwood, CS AF Roetker, Nicholas S. Yonker, James A. Lee, Chee Chang, Vicky Basson, Jacob J. Roan, Carol L. Hauser, Taissa S. Hauser, Robert M. Atwood, Craig S. TI Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study SO BMJ OPEN LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; DOPAMINE-RECEPTOR GENE; GENOME-WIDE ASSOCIATION; MAJOR DEPRESSION; ENVIRONMENT INTERACTION; ALZHEIMERS-DISEASE; HEALTHY-VOLUNTEERS; RISK-FACTORS; A1 ALLELE; BINDING AB Objectives: Single genetic loci offer little predictive power for the identification of depression. This study examined whether an analysis of gene-gene (G x G) interactions of 78 single nucleotide polymorphisms (SNPs) in genes associated with depression and age-related diseases would identify significant interactions with increased predictive power for depression. Design: A retrospective cohort study. Setting: A survey of participants in the Wisconsin Longitudinal Study. Participants: A total of 4811 persons (2464 women and 2347 men) who provided saliva for genotyping; the group comes from a randomly selected sample of Wisconsin high school graduates from the class of 1957 as well as a randomly selected sibling, almost all of whom are non-Hispanic white. Primary outcome measure: Depression as determine by the Composite International Diagnostic Interview-Short-Form. Results: Using a classification tree approach (recursive partitioning (RP)), the authors identified a number of candidate G x G interactions associated with depression. The primary SNP splits revealed by RP (ANKK1 rs1800497 (also known as DRD2 Taq1A) in men and DRD2 rs224592 in women) were found to be significant as single factors by logistic regression (LR) after controlling for multiple testing (p=0.001 for both). Without considering interaction effects, only one of the five subsequent RP splits reached nominal significance in LR (FTO rs1421085 in women, p=0.008). However, after controlling for G x G interactions by running LR on RP-specific subsets, every split became significant and grew larger in magnitude (OR (before)/(after): men: GNRH1 novel SNP: (1.43 -> 1.57); women: APOC3 rs2854116: (1.28 -> 1.55), ACVR2B rs3749386: (1.11 -> 2.17), FTO rs1421085: (1.32 -> 1.65), IL6 rs1800795: (1.12 -> 1.85)). Conclusions: The results suggest that examining G x G interactions improves the identification of genetic associations predictive of depression. 4 of the SNPs identified in these interactions were located in two pathways well known to impact depression: neurotransmitter (ANKK1 and DRD2) and neuroendocrine (GNRH1 and ACVR2B) signalling. This study demonstrates the utility of RP analysis as an efficient and powerful exploratory analysis technique for uncovering genetic and molecular pathway interactions associated with disease aetiology. C1 [Roetker, Nicholas S.; Yonker, James A.; Lee, Chee; Chang, Vicky; Roan, Carol L.; Hauser, Taissa S.; Hauser, Robert M.] Univ Wisconsin, Dept Sociol, Madison, WI 53706 USA. [Atwood, Craig S.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [Basson, Jacob J.; Atwood, Craig S.] Univ Wisconsin, Dept Med, Madison Sch Med & Publ Hlth, Madison, WI USA. [Atwood, Craig S.] Edith Cowan Univ, Sch Exercise Biomed & Hlth Sci, Joondalup, Australia. RP Atwood, CS (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. EM csa@medicine.wisc.edu RI Yonker, James/J-6561-2014 OI Yonker, James/0000-0002-9483-8511 FU National Institute on Aging [AG09775, AG21079, AG33285]; Vilas Estate Trust; National Science Foundation; Spencer Foundation; Graduate School of the University of Wisconsin-Madison FX This research uses data from the Wisconsin Longitudinal Study (WLS) of the University of Wisconsin-Madison. Since 1991, the WLS has been supported principally by the National Institute on Aging (AG09775, AG21079 and AG33285), with additional support from the Vilas Estate Trust, the National Science Foundation, the Spencer Foundation and the Graduate School of the University of Wisconsin-Madison. A public use file of data from the WLS is available from the Wisconsin Longitudinal Study, University of Wisconsin-Madison, 1180 Observatory Drive, Madison, Wisconsin 53706 and at http://www.ssc.wisc.edu/wlsresearch/data/. This material is the result of work supported with resources at the William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. The opinions expressed herein are those of the authors. The contents do not represent the views of the Department of Veterans Affairs or the US Government. This is Geriatrics Research, Education and Clinical Center VA paper # 2012-03. NR 40 TC 9 Z9 10 U1 1 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2012 VL 2 IS 4 AR e000944 DI 10.1136/bmjopen-2012-000944 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 091KW UT WOS:000315049300033 ER PT J AU Sanguansak, T Morley, MG Yospaiboon, Y Lorch, A Hedt, B Morley, K AF Sanguansak, Thuss Morley, Michael G. Yospaiboon, Yosanan Lorch, Alice Hedt, Bethany Morley, Katharine TI The impact of preprinted prescription forms on medication prescribing errors in an ophthalmology clinic in northeast Thailand: a non-randomised interventional study SO BMJ OPEN LA English DT Article ID PATTERNS AB Objectives: To understand the incidence and types of medication prescribing errors in a low resource setting ophthalmology clinic and to determine the impact of a preprinted prescription based on the hospital formulary (FormularyScript) on medication prescribing errors. Design: Non-randomised interventional study. Setting: Ophthalmology clinic in a teaching hospital in northeast Thailand. Participants: 4349 handwritten prescriptions collected from October 2009 to December 2009, and 4146 FormularyScripts collected from February 2010 to May 2010. Primary and secondary outcome measures: All prescriptions from the handwritten and FormularyScript groups were analysed for medication error rates by types (legibility, ambiguous, incomplete, abbreviation and accuracy) and subtypes (drug name, strength, which eye, route and dispensed amount). Results: Comparison of error rates in the two groups showed a 10-fold reduction in the overall error rate using FormularyScript (32.9%-3.5%, p<0.001). FormularyScripts were associated with statistically significant (p<0.001) decreases in the following error types: legibility (16.1%-0.1%), incomplete (16.1%-0.1%) and abbreviation (3.1%-0.3%). There was no statistically significant change in accuracy errors (0.8%-0.6%, p = 0.21). Ambiguous errors increased with FormularyScripts (0.6%-2.5%, p<0.001), likely due to the introduction of new ways to make errors. Decreases were seen in all legibility, abbreviation and accuracy error subtypes, and four out of six incomplete error subtypes. There were statistically significant increases in both ambiguous error subtypes: which eye (0.3%-2.5%, p<0.001) and drug name (0.3%-0.6%, p=0.03). Conclusions: In our study population, outpatient medication prescribing errors were common and primarily due to legibility and incomplete error types. A preprinted prescription form has the potential to decrease medication prescribing errors related to legibility, incomplete prescribing information and use of unacceptable abbreviations without changing the overall rate of accuracy errors. However, new error types can occur. C1 [Sanguansak, Thuss; Yospaiboon, Yosanan] Khon Kaen Univ, Srinagarind Hosp, Dept Ophthalmol, Khon Kaen, Thailand. [Morley, Michael G.] Harvard Univ, Sch Med, Ctr Eye Res & Educ, Ophthalm Consultants Boston, Boston, MA USA. [Lorch, Alice] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Hedt, Bethany] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Morley, Katharine] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Morley, K (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. EM kemorley@partners.org OI Yospaiboon, Yosanan/0000-0003-0081-0102 FU WHO [PS08169]; Center for Eye Research and Education FX This work was supported by the WHO Patient Safety Research Small Grants (PS08169 to TS) and the Center for Eye Research and Education. NR 11 TC 3 Z9 3 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2012 VL 2 IS 1 AR e000539 DI 10.1136/bmjopen-2011-000539 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 091GK UT WOS:000315037200048 PM 22365953 ER PT J AU Szentkiralyi, A Winter, AC Schurks, M Volzke, H Hoffmann, W Buring, JE Gaziano, JM Kurth, T Berger, K AF Szentkiralyi, Andras Winter, Anke C. Schuerks, Markus Voelzke, Henry Hoffmann, Wolfgang Buring, Julie E. Gaziano, J. Michael Kurth, Tobias Berger, Klaus TI Restless legs syndrome and all-cause mortality in four prospective cohort studies SO BMJ OPEN LA English DT Article ID CARDIOVASCULAR-DISEASE; GENERAL-POPULATION; PHYSICIANS HEALTH; RANDOMIZED-TRIAL; RLS EPIDEMIOLOGY; SLEEP DURATION; RISK-FACTORS; SYMPTOMS; ASSOCIATION; PREVALENCE AB Objectives: To evaluate the association between restless legs syndrome (RLS) and all-cause mortality. Design: Four prospective cohort studies. Setting: The Dortmund Health Study (DHS) and the Study of Health in Pomerania (SHIP) from Germany. The Women's Health Study (WHS) and the Physicians' Health Study (PHS) from the USA. Participants: In DHS: a random sample (n=1 299) from the population of Dortmund; in SHIP: a sample (n=4 291) from residents living in West Pomerania were drawn by multistage random sampling design; in WHS: female healthcare professionals (n=31 370); in PHS: male physicians (n=22 926) Main outcome measures: All-cause mortality. Results: The prevalence of RLS ranged between 7.4% and 11.9% at baseline. During follow-up (ranging between 6 and 11 years) RLS was not associated with increased risk of all-cause mortality in any of the four cohorts. The multivariable-adjusted HRs (95% CI) for all-cause mortality ranged from 0.21 (0.03 to 1.53) to 1.07 (0.93 to 1.23) across the four studies. The HRs for all-cause mortality did not differ according to gender. Conclusions: In these four independently conducted large prospective cohort studies from Germany and the USA, RLS did not increase the risk of all-cause mortality. These findings do not support the hypothesis that RLS is a risk factor for mortality of any cause. C1 [Szentkiralyi, Andras; Berger, Klaus] Univ Munster, Inst Epidemiol & Social Med, D-48149 Munster, Germany. [Szentkiralyi, Andras] Semmelweis Univ, Inst Behav Sci, Budapest, Hungary. [Winter, Anke C.; Buring, Julie E.; Gaziano, J. Michael; Kurth, Tobias] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med,Dept Med, Boston, MA 02115 USA. [Schuerks, Markus] Univ Hosp Essen, Dept Neurol, Essen, Germany. [Voelzke, Henry; Hoffmann, Wolfgang] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Hoffmann, Wolfgang] German Ctr Neurodegenerat Dis DZNE, Ctr Integrated Dementia Care Res CIDC, Greifswald, Germany. [Gaziano, J. Michael] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging,Dept Med, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Dept Med, Boston, MA USA. [Kurth, Tobias] INSERM, Neuroepidemiol U708, Bordeaux, France. [Kurth, Tobias] Univ Bordeaux, Bordeaux, France. RP Szentkiralyi, A (reprint author), Univ Munster, Inst Epidemiol & Social Med, D-48149 Munster, Germany. EM szentkir@uni-muenster.de RI Kurth, Tobias/A-9243-2012; OI Kurth, Tobias/0000-0001-7169-2620; Winter, Anke/0000-0001-8430-1334; Szentkiralyi, Andras/0000-0002-7892-2422 FU Almirall; Astra Zeneca; Berlin Chemie; Boehringer; Boots Health Care; Glaxo-Smith-Kline; Janssen Cilag; McNeil Pharma; MSD Sharp Dohme; Pfizer; Federal Ministry of Education and Research, Berlin [ZZ9603]; Ministers of Cultural and Social Affairs of the Federal State of Mecklenburg-West Pomerania, Schwerin; National Heart, Lung, and Blood Institute [HL-091880, HL-043851, HL-080467, HL-099355, HL-26490, HL-34595]; National Cancer Institute [CA-47988, CA-34944, CA-40360, CA-097193] FX Data collection in the Dortmund Health Study was supported by the German Migraine & Headache Society and by unrestricted grants of equal share from Almirall, Astra Zeneca, Berlin Chemie, Boehringer, Boots Health Care, Glaxo-Smith-Kline, Janssen Cilag, McNeil Pharma, MSD Sharp & Dohme and Pfizer to the University of Muenster.; SHIP is part of the Community Medicine Research Net of the University of Greifswald (available at http://medizin.uni-greifswfald.de/cm) and was funded by grant ZZ9603 from the Federal Ministry of Education and Research, Berlin, and the Ministers of Cultural and Social Affairs of the Federal State of Mecklenburg-West Pomerania, Schwerin.; The RLS research in the WHS and PHS is supported by a grant from the National Heart, Lung, and Blood Institute (HL-091880). The Women's Health Study is supported by grants from the National Heart, Lung, and Blood Institute (HL-043851, HL-080467, HL-099355), and the National Cancer Institute (CA-47988). The Physicians' Health Study is supported by grants from the National Cancer Institute (CA-34944, CA-40360 and CA-097193) and from the National Heart, Lung, and Blood Institute (HL-26490 and HL-34595). NR 31 TC 9 Z9 9 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2012 VL 2 IS 6 AR e001652 DI 10.1136/bmjopen-2012-001652 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 091WV UT WOS:000315081400076 ER PT J AU Bartels, CM Saucier, JM Thorpe, CT Kind, AJH Pandhi, N Hansen, KE Smith, MA AF Bartels, Christie M. Saucier, Jessica M. Thorpe, Carolyn T. Kind, Amy J. H. Pandhi, Nancy Hansen, Karen E. Smith, Maureen A. TI Monitoring diabetes in patients with and without rheumatoid arthritis: a Medicare study SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID POSITIVE PREDICTIVE-VALUE; TRADITIONAL RISK-FACTORS; QUALITY-OF-CARE; MYOCARDIAL-INFARCTION; ADMINISTRATIVE DATA; ORTHOPEDIC-SURGERY; COMORBIDITIES; CLAIMS; COMPLICATIONS; SENSITIVITY AB Introduction: Diabetes mellitus is a key predictor of mortality in rheumatoid arthritis (RA) patients. Both RA and diabetes increase the risk of cardiovascular disease (CVD), yet understanding of how comorbid RA impacts the receipt of guideline-based diabetes care is limited. The purpose of this study was to examine how the presence of RA affected hemoglobin A1C (A1c) and lipid measurement in older adults with diabetes. Methods: Using a retrospective cohort approach, we identified beneficiaries >= 65 years old with diabetes from a 5% random national sample of 2004 to 2005 Medicare patients (N = 256,331), then examined whether these patients had comorbid RA and whether they received guideline recommended A1c and lipid testing in 2006. Multivariate logistic regression was used to examine the effect of RA on receiving guideline recommended testing, adjusting for baseline sociodemographics, comorbidities and health care utilization. Results: Two percent of diabetes patients had comorbid RA (N = 5,572). Diabetes patients with comorbid RA were more likely than those without RA to have baseline cardiovascular disease (such as 17% more congestive heart failure), diabetes-related complications including kidney disease (19% higher), lower extremity ulcers (77% higher) and peripheral vascular disease (32% higher). In adjusted models, diabetes patients with RA were less likely to receive recommended A1c testing (odds ratio (OR) 0.84, CI 0.80 to 0.89) than those without RA, but were slightly more likely to receive lipid testing (OR 1.08, CI 1.01 to 1.16). Conclusions: In older adults with diabetes, the presence of comorbid RA predicted lower rates of A1c testing but slightly improved lipid testing. Future research should examine strategies to improve A1c testing in patients with diabetes and RA, in light of increased CVD and microvascular risks in patients with both conditions. C1 [Bartels, Christie M.; Hansen, Karen E.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Rheumatol Sect, Madison, WI 53792 USA. [Saucier, Jessica M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. [Saucier, Jessica M.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Dermatol, Madison, WI 53792 USA. [Thorpe, Carolyn T.] Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA 15240 USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Kind, Amy J. H.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Geriatr, Madison, WI 53792 USA. [Kind, Amy J. H.] William S Middleton Hosp, Geriatr Res Educ & Clin Ctr, US Dept Vet Affairs, Madison, WI 53705 USA. [Pandhi, Nancy] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI 53715 USA. [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI 53792 USA. [Smith, Maureen A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI 53792 USA. RP Bartels, CM (reprint author), Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Rheumatol Sect, 600 N Highland Ave, Madison, WI 53792 USA. EM cb4@medicine.wisc.edu FU NIH-NIAMS [K23AR062381]; Health Innovation Program and Community-Academic Partnerships core of UW Clinical and Translational Science Award; NIH- NCATS [9U54TR000021] FX The authors would like to thank Robert Purvis for meticulous data preparation and Rebecca Schwei, Kristin Slovenkay and Colleen Brown for manuscript preparation. This project was supported by a training grant NIH-NIAMS K23AR062381 and the Health Innovation Program and Community-Academic Partnerships core of UW Clinical and Translational Science Award, previously NIH-NCRR1UL1RR025011, now NIH-NCATS grant 9U54TR000021. The Health Innovation Program provided support for data collection, analysis and manuscript formatting. No other funding source had a role in the design; collection, analysis and interpretation of data; writing of the manuscript; or the decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 35 TC 9 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2012 VL 14 IS 4 AR R166 DI 10.1186/ar3915 PG 9 WC Rheumatology SC Rheumatology GA 090JF UT WOS:000314974600010 PM 22809064 ER PT J AU Gorth, DJ Mauck, RL Chiaro, JA Mohanraj, B Hebela, NM Dodge, GR Elliott, DM Smith, LJ AF Gorth, Deborah J. Mauck, Robert L. Chiaro, Joseph A. Mohanraj, Bhavana Hebela, Nader M. Dodge, George R. Elliott, Dawn M. Smith, Lachlan J. TI IL-1ra delivered from poly(lactic-co-glycolic acid) microspheres attenuates IL-1 beta-mediated degradation of nucleus pulposus in vitro SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; HUMAN INTERVERTEBRAL DISC; RHEUMATOID-ARTHRITIS; BACK-PAIN; INTRAARTICULAR INJECTION; THERAPEUTIC INTERVENTION; MATRIX DEGRADATION; PLGA MICROSPHERES; DEGENERATION; EXPRESSION AB Introduction: Inflammation plays a key role in the progression of intervertebral disc degeneration, a condition strongly implicated as a cause of lower back pain. The objective of this study was to investigate the therapeutic potential of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with interleukin-1 receptor antagonist (IL-1ra) for sustained attenuation of interleukin-1 beta (IL-1 beta) mediated degradative changes in the nucleus pulposus (NP), using an in vitro model. Methods: IL-1ra was encapsulated in PLGA microspheres and release kinetics were determined over 35 days. NP agarose constructs were cultured to functional maturity and treated with combinations of IL-1 beta and media conditioned with IL-1ra released from microspheres at intervals for up to 20 days. Construct mechanical properties, glycosaminoglycan content, nitrite production and mRNA expression of catabolic mediators were compared to properties for untreated constructs using unpaired Student's t-tests. Results: IL-1ra release kinetics were characterized by an initial burst release reducing to a linear release over the first 10 days. IL-1ra released from microspheres attenuated the degradative effects of IL-1 beta as defined by mechanical properties, glycosaminoglycans (GAG) content, nitric oxide production and mRNA expression of inflammatory mediators for 7 days, and continued to limit functional degradation for up to 20 days. Conclusions: In this study, we successfully demonstrated that IL-1ra microspheres can attenuate the degradative effects of IL-1 beta on the NP for extended periods. This therapeutic strategy may be appropriate for treating early-stage, cytokine-mediated disc degeneration. Ongoing studies are focusing on testing IL-1ra microspheres in an in vivo model of disc degeneration, as a prelude to clinical translation. C1 [Gorth, Deborah J.; Mauck, Robert L.; Chiaro, Joseph A.; Mohanraj, Bhavana; Dodge, George R.; Smith, Lachlan J.] Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. [Gorth, Deborah J.; Mauck, Robert L.; Chiaro, Joseph A.; Hebela, Nader M.; Dodge, George R.; Smith, Lachlan J.] Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Elliott, Dawn M.] Univ Delaware, Coll Engn, Dept Biomed Engn, Newark, DE 19716 USA. RP Smith, LJ (reprint author), Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, 424 Stemmler Hall,3450 Hamilton Walk, Philadelphia, PA 19104 USA. EM lachlans@mail.med.upenn.edu FU Department of Veterans Affairs Merit Grant [01RX000211]; Penn Center for Musculoskeletal Disorders FX This study was funded by a Department of Veterans Affairs Merit Grant (01RX000211) and the Penn Center for Musculoskeletal Disorders. 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 US government. NR 53 TC 24 Z9 26 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2012 VL 14 IS 4 AR R179 DI 10.1186/ar3932 PG 12 WC Rheumatology SC Rheumatology GA 090JF UT WOS:000314974600023 PM 22863285 ER PT J AU Singh, JA Lewallen, DG AF Singh, Jasvinder A. Lewallen, David G. TI Predictors of use of pain medications for persistent knee pain after primary Total Knee Arthroplasty: a cohort study using an institutional joint registry SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID SEVERE FUNCTIONAL LIMITATION; TOTAL HIP; AGE; REPLACEMENT; OUTCOMES; IMPACT; HOSPITALIZATIONS; DEPRESSION; MORBIDITY; PATTERNS AB Introduction: To study the use of pain medications for persistent index knee pain and their predictors after primary Total Knee Arthroplasty (TKA). Methods: The Mayo Total Joint Registry collects patient-reported data including pain medication use on all patients who undergo TKA. We used data from patients who underwent primary TKA from 1993-2005. We examined whether gender, age (reference, <= 60 yrs), body mass index (BMI; reference, <25 kg/m(2)), comorbidities measured by Deyo-Charlson index (5-point increase), anxiety and depression predicted use of pain medications (non-steroidal anti-inflammatory drugs (NSAIDs) and opioids) 2- and 5-years after primary TKA. Multivariable logistic regression additionally adjusted for operative diagnosis, American Society of Anesthesiologists (ASA) score, implant fixation and distance from the medical center. Results: 7,139 of the 10,957 eligible (65%) at 2-years and 4,234 of 7,404 eligible (57%) completed questionnaires. Significant predictors of NSAIDs use were (Odds ratio (95% confidence interval)): male gender at 2- and 5-years, 0.5 (0.4, 0.6) and 0.6 (0.5, 0.8); age >70-80 years, 0.7 (0.5, 0.9), 0.6 (0.4, 0.8); and depression, 1.4 (1.0, 1.8) and 1.7 (1.1, 2.5). BMI >= 40 was associated with NSAIDs use only at 2-years, 1.6 (1.1, 2.5). Significant predictors of opioid pain medication use at 2-and 5-years were: male gender, 0.5 (0.3, 0.9) and 0.4 (0.2, 0.8); age >70-80 years, 0.3 (0.1, 0.6), 0.3 (0.1, 0.8); and anxiety, 3.0 (1.6, 5.7) and 4.0 (1.7, 9.4). Conclusions: Female gender and younger age were associated with higher risk of use of NSAIDs and opioids after primary TKA. Depression was associated with higher NSAID use and anxiety with higher opioid pain medication use after primary TKA. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN 55905 USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU Mayo Clinic Orthopedic Surgery research funds; National Institutes of Health (NIH) [1 KL2 RR024151-01]; Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs); National Institute of Aging, National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Cancer Institute FX This material is the result of work supported with research grants from the Mayo Clinic Orthopedic Surgery research funds, National Institutes of Health (NIH) Clinical Translational Science Award 1 KL2 RR024151-01 (Mayo Clinic Center for Clinical and Translational Research) and the resources and use of facilities at the Birmingham VA Medical Center, Alabama, USA. JAS. is also supported by grants from the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), National Institute of Aging, National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS) and National Cancer Institute. NR 35 TC 13 Z9 13 U1 3 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2012 VL 14 IS 6 AR R248 DI 10.1186/ar4091 PG 9 WC Rheumatology SC Rheumatology GA 093LB UT WOS:000315192300024 PM 23157942 ER PT J AU Lin, YG Li, QZ Haldar, JP Leahy, RM AF Lin, Yanguang Li, Quanzheng Haldar, Justin P. Leahy, Richard M. GP IEEE TI CONSTRAINED MIXTURE MODELING FOR THE ESTIMATION OF KINETIC PARAMETERS IN DYNAMIC PET SO 2012 9TH IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) LA English DT Proceedings Paper CT 9th IEEE International Symposium on Biomedical Imaging (ISBI) - From Nano to Macro CY MAY 02-05, 2012 CL Barcelona, SPAIN SP IEEE, IEEE Engn Med & Biol Soc (EMBS), IEEE Signal Proc Soc DE Dynamic PET; Mixture Modeling; Sparsity; Kinetic Parameter Estimation ID RECONSTRUCTION AB The estimation and analysis of kinetic parameters in dynamic PET is frequently confounded by noise and partial volume effects. We propose a new constrained model of dynamic PET to address these limitations. The proposed formulation incorporates an explicit partial volume model in which each image voxel is represented as a mixture of different pure tissue types with distinct temporal dynamics. A two stage algorithm is proposed to solve the resulting problem. In the first stage, a sparse signal processing method is applied to estimate the rate parameters for the different tissue compartments from the noisy PET time series. In the second stage, tissue fractions and the linear parameters of different time activity curves (TACs) are estimated using a combination of sparsity, spatial-regularity, and fractional mixture constraints. A block coordinate descent (BCD) algorithm is combined with a manifold search to robustly estimate these parameters. The method is evaluated with both simulated and experimental dynamic PET data. C1 [Lin, Yanguang; Haldar, Justin P.; Leahy, Richard M.] Univ So Calif, Inst Signal & Image Proc, Los Angeles, CA 90089 USA. [Li, Quanzheng] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lin, YG (reprint author), Univ So Calif, Inst Signal & Image Proc, Los Angeles, CA 90089 USA. RI Haldar, Justin/B-4983-2008 OI Haldar, Justin/0000-0002-1838-0211 FU NIH [R21CA149587, R01EB010197] FX This work is supported by NIH grants R21CA149587 and R01EB010197. NR 12 TC 1 Z9 1 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4577-1858-8 PY 2012 BP 1004 EP 1007 PG 4 WC Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BDA85 UT WOS:000312384100259 ER PT J AU Stojanovic, I Pien, H Do, S Karl, WC AF Stojanovic, Ivana Pien, Homer Do, Synho Karl, W. Clem GP IEEE TI LOW-DOSE X-RAY CT RECONSTRUCTION BASED ON JOINT SINOGRAM SMOOTHING AND LEARNED DICTIONARY-BASED REPRESENTATION SO 2012 9TH IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) LA English DT Proceedings Paper CT 9th IEEE International Symposium on Biomedical Imaging (ISBI) - From Nano to Macro CY MAY 02-05, 2012 CL Barcelona, SPAIN SP IEEE, IEEE Engn Med & Biol Soc (EMBS), IEEE Signal Proc Soc DE Low-dose CT; sparse representation; sinogram smoothing; learning; overcomplete dictionary representations ID COMPUTED-TOMOGRAPHY; IMAGE-RECONSTRUCTION; REDUCTION; NOISE AB In this paper we propose two novel image reconstruction methods for low-dose X-ray CT data. Both approaches are based on anisotropic sinogram smoothing coupled with sparse local image representation with respect to a learned overcomplete dictionary. The redundant dictionary is learned from normal-dose CT training images and encodes artifact-free image behavior. The methods differ in the details of how the redundant dictionary information is included. Efficient solution approaches to the new formulations are provided. Comparative results on simulated low-dose imagery are given. Our approach is new in how it applies learning-based dictionary techniques to low-dose CT reconstruction, in its use of high quality training data in dictionary generation, and in its incorporation of anisotropic sinogram constraints together with the dictionary-based representation. C1 [Stojanovic, Ivana; Karl, W. Clem] Boston Univ, Boston, MA 02215 USA. [Pien, Homer; Do, Synho] Massachusetts Gen Hosp, Boston, MA USA. RP Stojanovic, I (reprint author), Boston Univ, Boston, MA 02215 USA. NR 12 TC 4 Z9 4 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4577-1858-8 PY 2012 BP 1012 EP 1015 PG 4 WC Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BDA85 UT WOS:000312384100261 ER PT J AU Zhang, YQ Karl, WC Van der Wilden, G Fagenholz, P Romero, J Noble, V Pien, H AF Zhang, Yaoqi Karl, W. Clem Van der Wilden, Gwendolyn Fagenholz, Peter Romero, Javier Noble, Vicki Pien, Homer GP IEEE TI AUTOMATED 3-D INTRAOCULAR ULTRASOUND DETECTION OF ELEVATED INTRACRANIAL PRESSURE SO 2012 9TH IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) LA English DT Proceedings Paper CT 9th IEEE International Symposium on Biomedical Imaging (ISBI) - From Nano to Macro CY MAY 02-05, 2012 CL Barcelona, SPAIN SP IEEE, IEEE Engn Med & Biol Soc (EMBS), IEEE Signal Proc Soc DE ultrasound; anisotropic diffusion; traumatic brain injury (TBI); optic nerve sheath diameter (ONSD); intracranial pressure (ICP) ID OPTIC-NERVE SHEATH AB Elevated intracranial pressure (ICP) is often associated with traumatic brain injury and can cause substantial complications. Elevated ICP also causes dilation of the optic nerve sheath, which can be observed and quantitated using intraocular ultrasound. We report on the use of 3-D ultrasound and automated processing algorithms to reduce operator variability in the assessment of sheath diameter. Using data from three subjects, we show that our approach appears to reduce operator variability by approximately 25%. These encouraging preliminary results support the development of an intraocular ultrasound system for non-invasive detection of elevated ICP. C1 [Zhang, Yaoqi; Karl, W. Clem] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. [Van der Wilden, Gwendolyn; Fagenholz, Peter; Noble, Vicki] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02215 USA. [Romero, Javier; Noble, Vicki; Pien, Homer] Harvard Med Sch, Boston, MA 02215 USA. [Romero, Javier; Pien, Homer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02215 USA. RP Zhang, YQ (reprint author), Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. NR 14 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4577-1858-8 PY 2012 BP 1571 EP 1574 PG 4 WC Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BDA85 UT WOS:000312384100406 ER PT J AU Bas, E Ataer-Cansizoglu, E Erdogmus, D Kalpathy-Cramer, J AF Bas, Erhan Ataer-Cansizoglu, Esra Erdogmus, Deniz Kalpathy-Cramer, Jayashree GP IEEE TI RETINAL VASCULATURE SEGMENTATION USING PRINCIPAL SPANNING FORESTS SO 2012 9TH IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) LA English DT Proceedings Paper CT 9th IEEE International Symposium on Biomedical Imaging (ISBI) - From Nano to Macro CY MAY 02-05, 2012 CL Barcelona, SPAIN SP IEEE, IEEE Engn Med & Biol Soc (EMBS), IEEE Signal Proc Soc DE Principal graphs; resampling on manifolds ID CURVES; IMAGES AB We propose an automated morphology reconstruction method for curvilinear network analysis. The proposed approach first projects samples to the ridge of the intensity image of the curvilinear system. Then, a manifold deviation measure is utilized to approximate the ridge with piecewise linear segments between the projected samples. A nonparametric system workflow based on the kernel interpolation and density estimation is provided for the derivations without any user defined meta-parameter, i.e. hard threshold for segmentation. Lastly, a rigorous sampling strategy using the manifold deviation measure that can be used for robust sparse tree reconstruction is provided. The proposed approaches have been tested on a small set of representative retinal scans. Preliminary qualitative results indicate the effectiveness of the method. C1 [Bas, Erhan] Howard Hughes Med Inst, Janelia Farm Res Ctr, Ashburn, VA 20147 USA. [Ataer-Cansizoglu, Esra; Erdogmus, Deniz] Northeastern Univ, Cognit Syst Lab, Boston, MA 02115 USA. [Kalpathy-Cramer, Jayashree] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Boston, MA 02115 USA. RP Bas, E (reprint author), Howard Hughes Med Inst, Janelia Farm Res Ctr, Ashburn, VA 20147 USA. OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618 FU NSF FX This work is partially supported by NSF. NR 15 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4577-1858-8 PY 2012 BP 1792 EP 1795 PG 4 WC Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BDA85 UT WOS:000312384100462 ER PT S AU Boboila, C Alt, FW Schwer, B AF Boboila, Cristian Alt, Frederick W. Schwer, Bjoern BE Alt, FW TI Classical and Alternative End-Joining Pathways for Repair of Lymphocyte-Specific and General DNA Double-Strand Breaks SO ADVANCES IN IMMUNOLOGY, VOL 116 SE Advances in Immunology LA English DT Review; Book Chapter ID CLASS-SWITCH RECOMBINATION; DEPENDENT PROTEIN-KINASE; SEVERE COMBINED IMMUNODEFICIENCY; XRCC4-DNA LIGASE-IV; CHROMOSOMAL TRANSLOCATION FORMATION; ANTIBODY DIVERSIFICATION ENZYME; INCREASED GENOMIC INSTABILITY; COMBINED IMMUNE-DEFICIENCY; LEAKY SCID PHENOTYPE; B-CELL LYMPHOMAS AB Classical nonhomologous end joining (C-NHEJ) is one of the two major known pathways for the repair of DNA double-strand breaks (DSBs) in mammalian cells. Our understanding of C-NHEJ has been derived, in significant part, through studies of programmed physiologic. DNA DSBs formed during V(D)J recombination in the developing immune system. Studies of immunoglobulin heavy-chain (IgH) class-switch recombination (CSR) also have revealed that there is an "alternative" end-joining process (A-EJ) that can function, relatively robustly, in the repair of DSBs in activated mature B lymphocytes. This A-EJ process has also been implicated in the formation of oncogenic translocations found in lymphoid tumors. In this review, we discuss our current understanding of C-NHEJ and A-EJ in the context of V(D)J recombination, CSR, and the formation of chromosomal translocations. C1 [Boboila, Cristian; Alt, Frederick W.; Schwer, Bjoern] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Boboila, Cristian; Alt, Frederick W.; Schwer, Bjoern] Harvard Univ, Sch Med, Dept Genet & Pediat, Boston, MA USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu; schwer@idi.harvard.edu FU Howard Hughes Medical Institute; NCI NIH HHS [5P01-CA109901-08, 5T32CA009382, P01 CA109901]; NIAID NIH HHS [2R01-AI0200047-30, 5P01-AI076210-4, 5R01-AI077595-4, P01 AI076210, R01 AI020047] NR 236 TC 107 Z9 110 U1 0 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 978-0-12-394300-2 J9 ADV IMMUNOL JI Adv.Immunol. PY 2012 VL 116 BP 1 EP 49 DI 10.1016/B978-0-12-394300-2.00001-6 PG 49 WC Immunology SC Immunology GA BDT11 UT WOS:000314729600001 PM 23063072 ER PT J AU Sharma, V Simpson, R LoPresti, E Schmeler, M AF Sharma, Vinod Simpson, Richard LoPresti, Edmund Schmeler, Mark TI Driving backwards using a semi-autonomous smart wheelchair system (DSS): A clinical evaluation SO APPLIED BIONICS AND BIOMECHANICS LA English DT Article DE Intelligent mobility aids (IMAs); collision avoidance; smart wheelchair; robotics; embedded distributed system; semi-autonomous system ID MOBILITY; RELIABILITY; VALIDATION; INSTRUMENT; COMMUNITY; FALLS; USERS; CARE AB Some wheelchair users have difficulty looking backward when backing up in confined spaces due to limited neck range of motion or low vision, which can lead to collisions which may result in personal injury or property damage. The Drive Safe System (DSS) was evaluated in a controlled laboratory setting with blindfolded able-bodied individuals on various backward driving tasks. Performance with the DSS was compared with a standard white cane used for navigation assistance by people with visual impairment. Results indicate that the DSS significantly reduced the number of collisions compared to using a cane (p = 0.0001) alone. There was no difference in task completion time when participants were using the cane or the DSS (p = 0.915). Users rated the DSS favourably as they experience less total workload (p = 0.026), less physical demand (p = 0.006), felt less frustrated (p = 0.002) and put less effort (p = 0.007) to achieve better performance when using the DSS, compared to using a cane. These findings suggest that the DSS can be a viable powered mobility solution for wheelchair users with visual impairments. C1 [Sharma, Vinod; Simpson, Richard] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15206 USA. [Sharma, Vinod; Simpson, Richard; Schmeler, Mark] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15206 USA. [Simpson, Richard] VA Pittsburgh Healthcare Syst, Human Engn Res Lab, Pittsburgh, PA USA. [LoPresti, Edmund] AT Sci, Pittsburgh, PA USA. RP Sharma, V (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Bakery Sq 853,6465 Penn Ave,Suite 401, Pittsburgh, PA 15206 USA. EM vks3@pitt.edu; ris20@pitt.edu; edlopresti@at-sciences.com; schmeler@pitt.edu RI Simpson, Richard/G-5683-2015 OI Simpson, Richard/0000-0002-6306-9393 FU NIH [5R44HD040023-03]; NSF [0540865] FX Tara Minkus assisted Dr. Sharma with data collection. This research was funded by the NIH (grant #5R44HD040023-03) and the NSF (grant #0540865). NR 43 TC 0 Z9 0 U1 5 U2 17 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1176-2322 J9 APPL BIONICS BIOMECH JI Appl. Bionics Biomech. PY 2012 VL 9 IS 4 BP 347 EP 365 DI 10.3233/ABB-2011-0012 PG 19 WC Engineering, Biomedical; Robotics SC Engineering; Robotics GA 084DC UT WOS:000314515800001 ER PT J AU Modak, A Durso, R Josephs, E Rosen, D AF Modak, Anil Durso, Raymon Josephs, Ephraim Rosen, David TI A Rapid Non Invasive L-DOPA-C-13 Breath Test for Optimally Suppressing Extracerebral AADC Enzyme Activity - Toward Individualizing Carbidopa Therapy in Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Parkinson's disease; personalized therapy; dopa decarboxylase; L-DOPA-C-13 breath test ID DIHYDROPYRIMIDINE DEHYDROGENASE-DEFICIENCY; AMINO-ACID DECARBOXYLASE; L-DOPA; MOTOR FLUCTUATIONS; HOMOVANILLIC-ACID; CENTRAL LEVODOPA; CLINICAL-TRIAL; METABOLISM; PHARMACOKINETICS; IDENTIFICATION AB Background: Peripheral carbidopa (CD) levels directly impact on central dopamine (DA) production in Parkinson disease (PD) through extracerebral inhibition of dopa decarboxylase (AADC) resulting in an increase in levodopa (LD) bioavailability. Objective: Recent data suggests that higher CD doses than those presently used in PD treatment may result in improved clinical response. Optimizing CD doses in individual patients may, therefore, result in ideal individualized treatment. Methods: A single center, randomized, double-blind study was carried out recruiting 5 Parkinson's disease (PD) patients already on LD/CD and 1 treatment naive PD patient using stable isotope labeled LD-1-C-13 as a substrate for a noninvasive breath test to evaluate individual AADC enzyme activity. Each patient was studied five times, receiving 200 mg LD-C-13 at each visit along with one of five randomized CD doses (0, 25, 50, 100 and 200 mg). The metabolite (CO2)-C-13 in breath was measured for evaluating AADC enzyme activity and plasma metabolite levels for LD-C-13 and homovanillic acid (HVA) were measured for 4 hours. Results: HVA in plasma and (CO2)-C-13 in breath are metabolic products of LD. We found a significant positive correlation of (CO2)-C-13 DOB AUC(0-240) with serum HVA AUC(0-240) following the oral dose of LD-1-C-13 for all 5 doses of CD (r(2) = 0.9378). With increasing inhibition of AADC enzyme activity with CD, we observed an increase in the plasma concentration of LD. We found an inverse correlation of the (CO2)-C-13 DOB AUC with serum LD-C-13 AUC. Our studies indicate the optimal dose of CD for maximal suppression of AADC enzyme activity can be determined for each individual from (CO2)-C-13 generation in breath. Conclusions: The LD-breath test can be a useful noninvasive diagnostic tool for evaluation of AADC enzyme activity using the biomarker (CO2)-C-13 in breath, a first step in personalizing CD doses for PD patients. C1 [Modak, Anil] Cambridge Isotope Labs Inc, Andover, MA 01830 USA. [Durso, Raymon; Josephs, Ephraim] VA Boston Healthcare Syst, Boston, MA USA. [Durso, Raymon] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Rosen, David] Phys Sci Inc, Andover, MA USA. RP Modak, A (reprint author), Cambridge Isotope Labs Inc, Andover, MA 01830 USA. EM anilm@isotope.com FU STTR from the National Institute of Neurological Disorders and Stroke [1R41NS063487] FX Supported by an STTR grant (1R41NS063487) from the National Institute of Neurological Disorders and Stroke. NR 32 TC 2 Z9 2 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2012 VL 2 IS 4 BP 349 EP 356 DI 10.3233/JPD-012132 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 084HR UT WOS:000314529900010 PM 23646099 ER PT J AU Collins, CE AF Collins, Corey E. BE Urman, RD Kaye, AD TI Pediatric sedation SO MODERATE AND DEEP SEDATION IN CLINICAL PRACTICE LA English DT Article; Book Chapter ID MECHANICAL VENTILATION; THERAPEUTIC PROCEDURES; CHILDREN; GUIDELINES; MANAGEMENT; UPDATE C1 Massachusetts Eye & Ear Infirm, Dept Anesthesiol, Boston, MA 02114 USA. RP Collins, CE (reprint author), Massachusetts Eye & Ear Infirm, Dept Anesthesiol, Boston, MA 02114 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-1-10740-045-0 PY 2012 BP 230 EP 244 D2 10.1017/CBO9781139084000 PG 15 WC Anesthesiology SC Anesthesiology GA BDI06 UT WOS:000313348800021 ER PT J AU Taylor, E AF Taylor, Eugene BE Charles, EP TI William James's Radical Empiricism: Did E. B. Holt Get It Right? SO NEW LOOK AT NEW REALISM: THE PSYCHOLOGY AND PHILOSOPHY OF E. B. HOLT LA English DT Article; Book Chapter C1 [Taylor, Eugene] Saybrook Univ, San Francisco, CA 94111 USA. [Taylor, Eugene] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Taylor, Eugene] Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. RP Taylor, E (reprint author), Saybrook Univ, San Francisco, CA 94111 USA. NR 31 TC 0 Z9 0 U1 1 U2 3 PU TRANSACTION PUBLISHERS PI PISCATAWAY PA RUTGERS UNIVERSITY, DEPT 8010, 35 BERRUE CIRCLE, PISCATAWAY, NJ 08854-8042 USA BN 978-1-4128-4561-8 PY 2012 BP 105 EP 126 PG 22 WC Psychology, Clinical; Philosophy SC Psychology; Philosophy GA BDI95 UT WOS:000313515900009 ER PT J AU McDonald, CC Tanenbaum, JB Lee, YC Fisher, DL Mayhew, DR Winston, FK AF McDonald, Catherine C. Tanenbaum, Jason B. Lee, Yi-Ching Fisher, Donald L. Mayhew, Daniel R. Winston, Flaura K. TI Using Crash Data to Develop Simulator Scenarios for Assessing Novice Driver Performance SO TRANSPORTATION RESEARCH RECORD LA English DT Article ID DRIVING SIMULATOR; EMPIRICAL-EVALUATION; HAZARD ANTICIPATION; RISK PERCEPTION; ON-ROAD; EXPERIENCE; DURATION; EVALUATE; SAFETY AB Teenage drivers are at their highest crash risk in their first 6 months or first 1,000 nil of driving. Driver training, adult-supervised practice driving, and other interventions are aimed at improving driving performance in novice drivers. Previous driver training programs have enumerated thousands of scenarios, with each scenario requiring one or more skills. Although there is general agreement about the broad set of skills needed to become a competent driver, there is no consensus set of scenarios and skills to assess whether novice drivers are likely to crash or to assess the effects of novice driver training programs on the likelihood of a crash. The authors propose that a much narrower, common set of scenarios can be used to focus on the high-risk crashes of young drivers. Until recently, it was not possible to identify the detailed set of scenarios that were specific to high-risk crashes. However, an integration of police crash reports from previous research, a number of critical simulator studies, and a nationally representative database of serious teen crashes (the National Motor Vehicle Crash Causation Survey) now make identification of these scenarios possible. In this paper, the authors propose this novel approach and discuss how to create a common set of simulated scenarios and skills to assess novice driver performance and the effects of training and interventions as they relate to high-risk crashes. C1 [McDonald, Catherine C.] Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Ctr Global Womens Hlth, Philadelphia, PA 19104 USA. [Tanenbaum, Jason B.; Lee, Yi-Ching; Winston, Flaura K.] Childrens Hosp Philadelphia, Div Gen Pediat, Ctr Injury Res & Prevent, Philadelphia, PA 19104 USA. [Fisher, Donald L.] Univ Massachusetts, Engn Lab 220A, Amherst, MA 01003 USA. [Mayhew, Daniel R.] Traff Injury Res Fdn, Ottawa, ON K2P 0B4, Canada. [Winston, Flaura K.] Univ Penn, Sch Med, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Winston, Flaura K.] Univ Penn, Sch Med, Perelman Sch Med, Leonard David Inst Hlth Econ, Philadelphia, PA 19104 USA. RP McDonald, CC (reprint author), Univ Penn, Sch Nursing, Ctr Hlth Equ Res, Ctr Global Womens Hlth, Claire Fagin Hall,418 Curie Blvd,233 2L, Philadelphia, PA 19104 USA. EM mcdonalc@nursing.upenn.edu FU Pennsylvania Department of Health; National Institute of Nursing Research through the T32 Award Program; T32 Award Program; Center for Injury Research and Prevention FX This project was funded, in part, by a grant from the Pennsylvania Department of Health. This research was also supported by a grant from the National Institute of Nursing Research through the T32 Award Program. Catherine C. McDonald, a postdoctoral fellow, was supported by the T32 Award Program. The authors thank Marilyn S. Sommers, Nancy Kassam-Adams, and the Center for Injury Research and Prevention for their support. The authors acknowledge Allison E. Curry and Michael J. Kallan for their assistance with the National Motor Vehicle Crash Causation Survey data The authors are also indebted to the National Highway Traffic Safety Administration for the efforts to provide the data available in the National Motor Vehicle Crash Causation Survey. NR 41 TC 5 Z9 5 U1 1 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0361-1981 J9 TRANSPORT RES REC JI Transp. Res. Record PY 2012 IS 2321 BP 73 EP 78 DI 10.3141/2321-10 PG 6 WC Engineering, Civil; Transportation; Transportation Science & Technology SC Engineering; Transportation GA 088TL UT WOS:000314859900011 PM 23543947 ER PT J AU Edmonds, ML Milan, SJ Camargo, CA Pollack, CV Rowe, BH AF Edmonds, Marcia L. Milan, Stephen J. Camargo, Carlos A., Jr. Pollack, Charles V. Rowe, Brian H. TI Early use of inhaled corticosteroids in the emergency department treatment of acute asthma SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE *Emergency Service, Hospital; Acute Disease; Administration, Inhalation; Adrenal Cortex Hormones [*administration & dosage]; Anti-Asthmatic Agents [*administration & dosage]; Asthma [*drug therapy]; Randomized Controlled Trials as Topic; Adult; Child; Humans ID NEBULIZED FLUTICASONE PROPIONATE; CONTROLLED CLINICAL-TRIAL; MODERATE ACUTE ASTHMA; DOUBLE-BLIND TRIAL; ORAL PREDNISONE; BECLOMETHASONE DIPROPIONATE; BRONCHIAL-ASTHMA; INTRAVENOUS HYDROCORTISONE; BUDESONIDE THERAPY; ROOM TREATMENT AB Background Systemic corticosteroid therapy is central to the management of acute asthma. The use of inhaled corticosteroids (ICS) may also be beneficial in this setting. Objectives To determine the benefit of ICS for the treatment of patients with acute asthma managed in the emergency department (ED). Search methods We identified controlled clinical trials from the Cochrane Airways Group specialised register of controlled trials. Bibliographies from included studies, known reviews, and texts also were searched. The latest search was September 2012. Selection criteria We included randomised controlled trials (RCTs) and quasi-RCTs. Studies were included if patients presented to the ED or its equivalent with acute asthma, and were treated with ICS or placebo, in addition to standard therapy. Two review authors independently selected potentially relevant articles, and then independently selected articles for inclusion. Methodological quality was independently assessed by two review authors. There were three different types of studies that were included in this review: 1) studies comparing ICS vs. placebo, with no systemic corticosteroids given to either treatment group, 2) studies comparing ICS vs. placebo, with systemic corticosteroids given to both treatment groups, and 3) studies comparing ICS alone versus systemic corticosteroids. For the analysis, the first two types of studies were included as separate subgroups in the primary analysis (ICS vs. placebo), while the third type of study was included in the secondary analysis (ICS vs. systemic corticosteroid). Data collection and analysis Data were extracted independently by two review authors if the authors were unable to verify the validity of extracted information. Missing data were obtained from the authors or calculated from other data presented in the paper. Where appropriate, individual and pooled dichotomous outcomes were reported as odds ratios (OR) with 95% confidence intervals (CIs). Where appropriate, individual and pooled continuous outcomes were reported as mean differences (MD) or standardized mean differences (SMD) with 95% CIs. The primary analysis employed a fixed-effect model and a random-effects model was used for sensitivity analysis. Heterogeneity is reported using I-squared (I-2) statistics. Main results Twenty trials were selected for inclusion in the primary analysis (13 paediatric, seven adult), with a total number of 1403 patients. Patients treated with ICS were less likely to be admitted to hospital (OR 0.44; 95% CI 0.31 to 0.62; 12 studies; 960 patients) and heterogeneity (I-2 = 27%) was modest. This represents a reduction from 32 to 17 hospital admissions per 100 patients treated with ICS in comparison with placebo. Subgroup analysis of hospital admissions based on concomitant systemic corticosteroid use revealed that both subgroups indicated benefit from ICS in reducing hospital admissions (ICS and systemic corticosteroid versus systemic corticosteroid: OR 0.54; 95% CI 0.36 to 0.81; 5 studies; N = 433; ICS versus placebo: OR 0.27; 95% CI 0.14 to 0.52; 7 studies; N = 527). However, there was moderate heterogeneity in the subgroup using ICS in addition to systemic steroids (I-2 = 52%). Patients receiving ICS demonstrated small, significant improvements in peak expiratory flow (PEF: MD 7%; 95% CI 3% to 11%) and forced expiratory volume in one second (FEV1: MD 6%; 95% CI 2% to 10%) at three to four hours post treatment). Only a small number of studies reported these outcomes such that they could be included in the meta-analysis and most of the studies in this comparison did not administer systemic corticosteroids to either treatment group. There was no evidence of significant adverse effects from ICS treatment with regard to tremor or nausea and vomiting. In the secondary analysis of studies comparing ICS alone versus systemic corticosteroid alone, heterogeneity among the studies complicated pooling of data or drawing reliable conclusions. Authors' conclusions ICS therapy reduces hospital admissions in patients with acute asthma who are not treated with oral or intravenous corticosteroids. They may also reduce admissions when they are used in addition to systemic corticosteroids; however, the most recent evidence is conflicting. There is insufficient evidence that ICS therapy results in clinically important changes in pulmonary function or clinical scores when used in acute asthma in addition to systemic corticosteroids. Also, there is insufficient evidence that ICS therapy can be used in place of systemic corticosteroid therapy when treating acute asthma. Further research is needed to clarify the most appropriate drug dosage and delivery device, and to define which patients are most likely to benefit from ICS therapy. Use of similar measures and reporting methods of lung function, and a common, validated, clinical score would be helpful in future versions of this meta-analysis. C1 [Edmonds, Marcia L.] Schulich Sch Med & Dent, London, ON N6A 5W9, Canada. [Milan, Stephen J.] Univ London, London, England. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Pollack, Charles V.] Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. [Rowe, Brian H.] Univ Alberta, Sch Publ Heath, Edmonton, AB, Canada. RP Edmonds, ML (reprint author), Schulich Sch Med & Dent, 800 Commissioners Rd E1-102, London, ON N6A 5W9, Canada. EM medmonds@ualberta.ca FU AstraZeneca; Boehringer-Ingelheim; Forest; GlaxoSmithKline; Merck; Sepracor; GSK; MedImmune Inc.; Department of Emergency Medicine, University of Alberta, Edmonton, AB, Canada; National Institute for Health Research, UK; National Institutes of Health, Bethesda, MD, USA [HL-03533]; Canadian Institutes of Health Research (CIHR), Ottawa, ON, Canada FX The review authors who have been involved in this review have done so without any known conflicts of interest. They are not involved with the primary studies. Drs. Camargo, Pollack have received unrestricted educational grants for research from AstraZeneca, Boehringer-Ingelheim, Forest, GlaxoSmithKline, Merck and Sepracor. In the past three years, Dr. Rowe has participated in trials sponsored by GSK and MedImmune Inc. None of the authors, however, are considered paid consultants by any pharmaceutical company that produces ICS agents.; Internal sources; Department of Emergency Medicine, University of Alberta, Edmonton, AB, Canada.; National Institute for Health Research (SJM), UK.; External sources; National Institutes of Health (HL-03533) Bethesda, MD (Dr. CA Camargo, Jr), USA.; Canadian Institutes of Health Research (CIHR), Ottawa, ON (BH Rowe), Canada. NR 141 TC 3 Z9 3 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2012 IS 12 AR CD002308 DI 10.1002/14651858.CD002308.pub2 PG 113 WC Medicine, General & Internal SC General & Internal Medicine GA 053FH UT WOS:000312255900023 ER PT J AU Travers, AH Milan, SJ Jones, AP Camargo, CA Rowe, BH AF Travers, Andrew H. Milan, Stephen J. Jones, Arthur P. Camargo, Carlos A., Jr. Rowe, Brian H. TI Addition of intravenous beta(2)-agonists to inhaled beta(2)-agonists for acute asthma SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID CHILDHOOD STATUS-ASTHMATICUS; SUBCUTANEOUS EPINEPHRINE; DOUBLE-BLIND; INITIAL TREATMENT; CONTROLLED-TRIAL; PROSPECTIVE MULTICENTER; NEBULIZED TERBUTALINE; SALBUTAMOL ALBUTEROL; RESPIRATORY-FAILURE; IV AMINOPHYLLINE AB Background Inhaled beta-agonist therapy is central to the management of acute asthma. This review evaluates the benefit of an additional use of intravenous beta(2)-agonist agents. Objectives To determine the benefit of adding intravenous (IV) beta(2)-agonists to inhaled beta(2)-agonist therapy for acute asthma treated in the emergency department. Search methods Randomised controlled trials (RCTs) were identified using the Cochrane Airways Group Register which is a compilation of systematic searches of MEDLINE, EMBASE, CINAHL, and CENTRAL as well as handsearching of 20 respiratory journals. Bibliographies from included studies and known reviews were also searched. Primary authors and content experts were contacted to identify eligible studies. The search was performed in September 2012. Selection criteria Only RCTs were considered for inclusion. Studies were included if patients presented to the emergency department with acute asthma and were treated with IV beta(2)-agonists with inhaled beta(2)-agonist therapy and existing standard treatments versus inhaled beta(2)-agonists and existing standard treatments. Data collection and analysis Two review authors independently extracted data and confirmed their findings with corresponding authors of trials. We obtained missing data from authors or calculated from data present in the papers. We used fixed-effect model for odds ratios (OR) and for mean differences (MD) we used both fixed-effect and random-effects models and reported 95% confidence intervals (CI). Main results From 109 potentially relevant studies only three (104 patients) met our inclusion criteria: Bogie 2007 (46 children), Browne 1997 (29 children) and Nowak 2010 (29 adults). Bogie 2007 investigated the addition of intravenous terbutaline to high dose nebulised albuterol in children with acute severe asthma, requiring intensive care unit (ICU) admission. Browne 1997 investigated the benefit of adding intravenous salbutamol to inhaled salbutamol in children with acute severe asthma in the emergency department. Nowak 2010 investigated addition of IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids) among adults, and was reported as a conference abstract only. There was no significant advantage (OR 0.29; 95% CI 0.06 to 1.38, one trial, 29 adults) for adding IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids) with regard to hospitalisation rates. Various outcome indicators for the length of stay were reported among the trials. Browne 1997 reported a significantly shorter recovery time (in terms of cessation of 30 minute salbutamol) for children in the IV salbutamol with inhaled salbutamol group (four hours) versus the 11.1 hours for the inhaled salbutamol group (P = 0.03). Time to cessation of hourly nebuliser was also significantly shorter (P = 0.02) for the IV plus inhaled salbutamol group (11.5 hours versus 21.2 hours), and they were ready for emergency patient discharge on average 9.7 hours earlier than the inhaled salbutamol group (P < 0.05). In a paediatric ICU study Bogie 2007 reported no significant advantage in length of paediatric ICU admission (hours) for adding IV terbutaline to nebulised albuterol (MD -12.95, 95% CI: -38.74, 12.84). Browne 1997 reported there were only six out of 14 children with a pulmonary index score above six in the IV plus inhaled salbutamol group at two hours compared with 14 of the 15 in the inhaled salbutamol group (P = 0.02) In Browne 1997 there was a higher proportion of tremor in the IV plus inhaled salbutamol group than in the inhaled salbutamol group (P < 0.02). Nowak 2010 did not report any statistically significant adverse effects associated with adding IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids). Troponin levels were elevated in three children in the IV terbutaline + nebulised albuterol group at 12 and 24 hours in Bogie 2007 Authors' conclusions There is very limited evidence from one study (Browne 1997) to support the use of IV beta(2)-agonists in children with severe acute asthma with respect to shorter recovery time, and similarly there is limited evidence (again from one study Browne 1997) suggesting benefit with regard to pulmonary index scores; however this advantage needs to be considered carefully in relation to the increased side effects associated with IV beta(2)-agonists. We identified no significant benefits for adults with severe acute asthma. Until more, adequately powered, high quality clinical trials in this area are conducted it is not possible to form a robust evaluation of the addition of IV beta(2)-agonists in children or adults with severe acute asthma. C1 [Travers, Andrew H.] Emergency Hlth Serv, Dept Emergency Med & Community Hlth & Epidemiol, Halifax, NS, Canada. [Milan, Stephen J.] Univ London, London, England. [Jones, Arthur P.] Cochrane Airways Grp, London, England. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. [Rowe, Brian H.] Univ Alberta, Sch Publ Heath, Edmonton, AB, Canada. RP Travers, AH (reprint author), Emergency Hlth Serv, Dept Emergency Med & Community Hlth & Epidemiol, Halifax, NS, Canada. EM Andrew.Travers@gov.ns.ca FU University of Alberta, Faculty of Medicine & Dentistry, Canada; Alberta Heritage Foundation for Medical Research (AHFMR), Canada; NHS Research and Development, UK; National Institute for Health Research, UK; Canadian Association of Emergency Physicians (CAEP), Canada; National Heart, Lung and Blood Institute (NIH; CA Camargo, Jr), USA [HL-03533]; Canadian Institutes of Health Research (CIHR), Ottawa, ON (BH Rowe), Canada FX Internal sources; University of Alberta, Faculty of Medicine & Dentistry, Canada.; Alberta Heritage Foundation for Medical Research (AHFMR), Canada.; NHS Research and Development, UK.; National Institute for Health Research (SJM), UK.; External sources; Canadian Association of Emergency Physicians (CAEP), Canada.; National Heart, Lung and Blood Institute (HL-03533 NIH; CA Camargo, Jr), USA.; Canadian Institutes of Health Research (CIHR), Ottawa, ON (BH Rowe), Canada. NR 123 TC 7 Z9 7 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2012 IS 12 AR CD010179 DI 10.1002/14651858.CD010179 PG 38 WC Medicine, General & Internal SC General & Internal Medicine GA 053FH UT WOS:000312255900017 ER PT J AU Travers, AH Jones, AP Camargo, CA Milan, SJ Rowe, BH AF Travers, Andrew H. Jones, Arthur P. Camargo, Carlos A., Jr. Milan, Stephen J. Rowe, Brian H. TI Intravenous beta(2)-agonists versus intravenous aminophylline for acute asthma SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID CHILDHOOD STATUS-ASTHMATICUS; SUBCUTANEOUS EPINEPHRINE; EMERGENCY-DEPARTMENT; INITIAL TREATMENT; CONTROLLED-TRIAL; DOUBLE-BLIND; NEBULIZED TERBUTALINE; SALBUTAMOL ALBUTEROL; RESPIRATORY-FAILURE; INHALED TERBUTALINE AB Background Inhaled beta(2)-agonist therapy is central to the management of acute asthma. For rapid bronchodilation in severe cases, penetration of inhaled drug to the affected small conducting airway may be impeded, and the intravenous (IV) rather than inhaled administration of bronchodilators may provide an earlier response. IV beta(2)-agonist agents and IV aminophylline may also be considered as additional interventions in this setting and this review compares IV beta-agonist agents and IV aminophylline in the treatment of people with acute asthma. Objectives To compare the benefit of IV beta(2)-agonists versus IV aminophylline for acute asthma treated in the emergency department and in patients admitted to hospital with acute severe asthma. Search methods Randomised controlled trials (RCTs) were identified using the Cochrane Airways Group Register, which is compiled from systematic searches of bibliographic databases as well as handsearching of respiratory journals and conference abstracts. The latest search was run in September 2012. We searched bibliographies from included studies and known reviews were also searched. Primary authors and content experts were contacted to identify eligible studies. Selection criteria We included RCTs of patients who presented to the emergency department with acute asthma, and patients admitted to hospital with acute severe asthma, and were treated with IV beta(2)-agonists versus IV aminophylline. Two review authors independently selected potentially relevant articles and selected articles for inclusion. Methodological quality was independently assessed using two scoring systems and two review authors. Data collection and analysis Data were extracted independently by two review authors. Missing data were obtained from authors or calculated from data present in the papers. Trials were combined using a random-effects model for odds ratios (OR) or mean differences (MD) and reported with 95% confidence intervals (95% CI). Main results Eleven studies met our inclusion criteria and in total they included 350 patients. However, opportunities to combine these studies in meta-analyses were limited by the variations in the range of outcomes reported in the trials. Length of stay Two studies reported length of stay. They were both paediatric trials (with one in paediatric intensive care unit), and there was no significant difference between the two groups (MD 23.19 hours; 95% CI -2.40 to 48.77 hours; 2 studies; N = 73). Individual separate MD analyses for the two studies also indicated no significant difference between the aminophylline and beta(2)-agonist on this outcome. However, this finding should be interpreted with caution owing to the small number of trials and participants the analysis. Pulmonary function There were no significant differences in the sequential or summative pulmonary function demonstrated across the studies. Heart rate Data for serial heart rates were reported in three studies at various points from 15 to 60 minutes and in each case there were no significant differences between people in the IV aminophylline or beta(2)-agonist groups. The difference between the two groups with respect to final heart rate was statistically significant (MD 10.00; 95% CI 0.99 to 19.01), although these data are from a single, small study and should be interpreted with caution. Adverse effects The analyses for giddiness (OR 59.22; 95% CI 2.80 to 1253.05; 1 study; N = 30), nausea/vomiting (where reported as a combined outcome) (OR 14.18; 95% CI 1.62 to 124.52; 2 studies; N = 96) and nausea (OR 6.53; 95% CI 1.60 to 26.72; 2 studies; N = 49) all significantly favoured beta(2)-agonists. In view of the very small number of studies and number of patients contributing to these analyses these results should be interpreted with caution. A closely related review considering the possible benefits of adding IV aminophylline to beta-agonists in adults with acute asthma also indicates a higher incidence of adverse effects associated with IV aminophylline. Authors' conclusions In the included RCTs there was no consistent evidence favouring either IV beta(2)-agonists or IV aminophylline for patients with acute asthma. The opportunity to draw clear conclusions is limited by the heterogeneity of outcomes evaluated and the small sample sizes in the included studies. It is recommended that these data should be viewed carefully alongside the conclusions from separate Cochrane reviews comparing IV beta(2)-agonists plus inhaled beta(2)-agonists versus inhaled beta(2)-agonists alone and IV aminophylline plus inhaled beta(2)-agonists versus inhaled beta(2)-agonists alone. C1 [Milan, Stephen J.] Univ London, London, England. [Travers, Andrew H.] Emergency Hlth Serv, Dept Emergency Med & Community Hlth & Epidemiol, Halifax, NS, Canada. [Jones, Arthur P.] Cochrane Airways Grp, London, England. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. [Rowe, Brian H.] Univ Alberta, Sch Publ Heath, Edmonton, AB, Canada. RP Milan, SJ (reprint author), Univ London, London, England. EM smilan@sgul.ac.uk FU University of Alberta, Faculty of Medicine & Dentistry, Canada; Alberta Heritage Foundation for Medical Research (AHFMR), Canada; NHS Research and Development, UK; National Institute of Health Research, UK; Canadian Association of Emergency Physicians (CAEP), Canada; National Heart, Lung and Blood Institute (NIH; CA Camargo, Jr), USA [HL-03533]; Canadian Institutes of Health Research (CIHR), Ottawa, ON (BH Rowe), Canada FX Internal sources; University of Alberta, Faculty of Medicine & Dentistry, Canada.; Alberta Heritage Foundation for Medical Research (AHFMR), Canada.; NHS Research and Development, UK.; National Institute of Health Research (SJM), UK.; External sources; Canadian Association of Emergency Physicians (CAEP), Canada.; National Heart, Lung and Blood Institute (HL-03533 NIH; CA Camargo, Jr), USA.; Canadian Institutes of Health Research (CIHR), Ottawa, ON (BH Rowe), Canada. NR 124 TC 3 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2012 IS 12 AR CD010256 DI 10.1002/14651858.CD010256 PG 60 WC Medicine, General & Internal SC General & Internal Medicine GA 053FH UT WOS:000312255900018 ER PT J AU Orini, M Bailon, R Laguna, P Mainardi, LT Barbieri, R AF Orini, Michele Bailon, Raquel Laguna, Pablo Mainardi, Luca T. Barbieri, Riccardo TI A multivariate time-frequency method to characterize the influence of respiration over heart period and arterial pressure SO EURASIP JOURNAL ON ADVANCES IN SIGNAL PROCESSING LA English DT Article DE Cross time-frequency analysis; Cardiovascular interactions; Baroreflex; Partial coherence; Phase difference ID SINUS ARRHYTHMIA; BAROREFLEX MECHANISM; CARDIOVASCULAR REGULATION; RATE-VARIABILITY; BLOOD-PRESSURE; HUMANS; REPRESENTATIONS; COHERENCE; SIGNALS; CAUSALITY AB Respiratory activity introduces oscillations both in arterial pressure and heart period, through mechanical and autonomic mechanisms. Respiration, arterial pressure, and heart period are, generally, non-stationary processes and the interactions between them are dynamic. In this study we present a methodology to robustly estimate the time course of cross spectral indices to characterize dynamic interactions between respiratory oscillations of heart period and blood pressure, as well as their interactions with respiratory activity. Time-frequency distributions belonging to Cohen's class are used to estimate time-frequency (TF) representations of coherence, partial coherence and phase difference. The characterization is based on the estimation of the time course of cross spectral indices estimated in specific TF regions around the respiratory frequency. We used this methodology to describe the interactions between respiration, heart period variability (HPV) and systolic arterial pressure variability (SAPV) during tilt table test with both spontaneous and controlled respiratory patterns. The effect of selective autonomic blockade was also studied. Results suggest the presence of common underling mechanisms of regulation between cardiovascular signals, whose interactions are time-varying. SAPV changes followed respiratory flow both in supine and standing positions and even after selective autonomic blockade. During head-up tilt, phase differences between respiration and SAPV increased. Phase differences between respiration and HPV were comparable to those between respiration and SAPV during supine position, and significantly increased during standing. As a result, respiratory oscillations in SAPV preceded respiratory oscillations in HPV during standing. Partial coherence was the most sensitive index to orthostatic stress. Phase difference estimates were consistent among spontaneous and controlled breathing patterns, whereas coherence was higher in spontaneous breathing. Parasympathetic blockade did not affect interactions between respiration and SAPV, reduced the coherence between SAPV and HPV and between respiration and HPV. Our results support the hypothesis that non-autonomic, possibly mechanically mediated, mechanisms also contributes to the respiratory oscillations in HPV. A small contribution of sympathetic activity on HPV-SAPV interactions around the respiratory frequency was also observed. C1 [Orini, Michele; Bailon, Raquel; Laguna, Pablo] Univ Zaragoza, Commun Technol Grp GTC, Aragon Inst Engn Res I3A, Zaragoza 50018, Spain. [Orini, Michele; Bailon, Raquel; Laguna, Pablo] Aragon Hlth Sci Inst, CIBER Bioingn Biomat & Nanomed CIBER BBN, Zaragoza, Spain. [Orini, Michele; Mainardi, Luca T.] Politecn Milan, Dept Bioengn, I-20131 Milan, Italy. [Orini, Michele; Barbieri, Riccardo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Orini, M (reprint author), Univ Zaragoza, Commun Technol Grp GTC, Aragon Inst Engn Res I3A, M Luna 1, Zaragoza 50018, Spain. EM michele@unizar.es RI Orini, Michele/K-9234-2014; Orini, Michele/H-3937-2015; OI Orini, Michele/0000-0001-5773-0344; Orini, Michele/0000-0001-5773-0344; Bailon, Raquel/0000-0003-1272-0550 FU NIH [R01-HL084502]; Ministerio de Ciencia e Innovacion, Spain [TEC2010-21703-C03-02, TRA2009-0127]; Diputacion General de Aragon, Spain, through Grupos Consolidados GTC [T30]; Instituto de Salud Carlos III, Spain, through CIBER [CB06/01/0062]; Instituto de Salud Carlos III, Spain, through ARAID; Ibercaja under project "Programa de apoyo a la I+D+i" FX Thanks to Dr. JP Saul and Dr. A Minchole for providing the authors with TTSR, TTCB, and ABCR data sets. This study was supported in part by NIH Grants R01-HL084502, Ministerio de Ciencia e Innovacion, Spain, under Projects TEC2010-21703-C03-02 and TRA2009-0127, Diputacion General de Aragon, Spain, through Grupos Consolidados GTC ref:T30, Instituto de Salud Carlos III, Spain, through CIBER CB06/01/0062, and ARAID and Ibercaja under project "Programa de apoyo a la I+D+i". NR 54 TC 6 Z9 6 U1 0 U2 6 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1687-6180 J9 EURASIP J ADV SIG PR JI EURASIP J. Adv. Signal Process. PY 2012 AR 214 DI 10.1186/1687-6180-2012-214 PG 17 WC Engineering, Electrical & Electronic SC Engineering GA 082UX UT WOS:000314419000001 ER PT S AU Citi, L Valenza, G Barbieri, R AF Citi, Luca Valenza, Gaetano Barbieri, Riccardo GP IEEE TI Instantaneous Estimation of High-Order Nonlinear Heartbeat Dynamics by Lyapunov Exponents SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE ID RATE-VARIABILITY; TIME-SERIES; IDENTIFICATION; ALGORITHM; SYSTEMS; CHAOS AB This paper introduces a novel methodology able to provide time varying estimates of the Lyapunov Spectrum within a point process framework. The algorithm is applied to ECG-derived data to characterize heartbeat nonlinear dynamics by using a cubic autoregressive point process model. Estimation of the model parameters is ensured by the Laguerre expansion of the Wiener-Volterra kernels along with a maximum local log-likelihood procedure. In addition to the instantaneous Lyapunov exponents, as well as indices related to higher order dynamic polyspectra, our method is also able to provide all the instantaneous time domain and frequency domain measures of instantaneous heart rate (HR) and heart rate variability (HRV) previously considered. Experimental results show that our method is able to track complex cardiovascular control dynamics during fast transitional gravitational changes. C1 [Citi, Luca; Valenza, Gaetano; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Citi, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM lciti@neurostat.mit.edu; g.valenza@ieee.org; barbieri@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833; Valenza, Gaetano/0000-0001-6574-1879 NR 24 TC 12 Z9 12 U1 0 U2 5 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 13 EP 16 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296500004 ER PT S AU Valenza, G Citi, L Scilingo, EP Barbieri, R AF Valenza, Gaetano Citi, Luca Scilingo, Enzo Pasquale Barbieri, Riccardo GP IEEE TI Using Laguerre Expansion within Point-Process Models of Heartbeat Dynamics: A Comparative Study SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE ID GAUSSIAN INPUTS; IDENTIFICATION AB Point-process models have been recognized as a distinguished tool for the instantaneous assessment of heartbeat dynamics. Although not thoroughly linked to the physiology, nonlinear models also yield a more accurate quantification of cardiovascular control dynamics. Here, we propose a Laguerre expansion of the linear and nonlinear Wiener-Volterra kernels in order to account for the nonlinear and non-gaussian information contained in the ECG-derived heartbeat series while using a reduced number of parameters. Within an Inverse-Gaussian probability model, up to quadratic nonlinearities were considered to continuously estimate the dynamic spectrum and bispectrum. Results performed on 10 subjects undergoing a stand-up protocol show that this novel methodology improves on the algorithmic performances and, at the same time, more accurately characterizes sympatho-vagal changes to posture. C1 [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Scilingo, Enzo Pasquale] Univ Pisa, Dept Informat Engn, I-56100 Pisa, Italy. RP Citi, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM g.valenza@ieee.org; lciti@neurostat.mit.edu; e.scilingo@centropiaggio.unipi.it; barbieri@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833; Scilingo, Enzo Pasquale/0000-0003-2588-4917; Valenza, Gaetano/0000-0001-6574-1879 FU NIH [R01-HL084502]; EU Commission [ICT-247777] FX We are grateful to Roger G. Mark and Thomas Heldt ( Harvard- MIT Division of Health Sciences and Technology) for kindly providing the experimental data. The study was supported in part by NIH Grant R01-HL084502 and by the EU Commission under contract ICT-247777 Psyche. NR 14 TC 5 Z9 5 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 29 EP 32 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296500008 ER PT S AU Bonmassar, G Iacono, MI Lev, MH AF Bonmassar, Giorgio Iacono, Maria Ida Lev, Michael H. GP IEEE TI Dual Energy Pulses for Electrical Impedance Spectroscopy with the Stochastic Gabor Function SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE AB This paper introduces the stochastic Gabor function (SGF), an excitation waveform that can be used to design optimal excitation pulses for Electrical Impedance Spectroscopy (EIS) of the brain. The SGF is a Gaussian function modulated by uniformly distributed noise; it has wide frequency spectrum representation regardless of the stimuli pulse length. The SGF was studied in the time-frequency domain. As shown by frequency concentration measurements, the SGF is least compact in the sample frequency phase plane. Numerical results obtained by using a realistic human head model indicate that the SGF may allow for both shallow and deeper tissue penetration than is currently obtainable with conventional stimulus paradigms, potentially facilitating tissue subtraction assessment of parenchymal dielectric changes in frequency. This could be of value in advancing EIS of stroke and hemorrhage. C1 [Bonmassar, Giorgio; Iacono, Maria Ida] Harvard Univ, Sch Med, AA Martinos Ctr, Charlestown, MA 02129 USA. [Lev, Michael H.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. RP Bonmassar, G (reprint author), Harvard Univ, Sch Med, AA Martinos Ctr, Charlestown, MA 02129 USA. EM giorgio@nmr.mgh.harvard.edu; iacono@nmr.mgh.harvard.edu; mlev@partners.org FU NBIB, NIH Subcontract through U of Cincinnati [5U54EB007954-04, 005213]; Massachusetts General Hos-pital Clinical Research Center [1 UL1 RR025758-01] FX Research supported by the NBIB, NIH Subcontract through U of Cincinnati (5U54EB007954-04 sub award 005213) "Point-of-care" Center (POC- CENT) and the Massachusetts General Hos-pital Clinical Research Center (No. 1 UL1 RR025758-01) Harvard Clinical and Translational Science Center, from the National Center for Research Resources. NR 6 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 138 EP 141 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296500035 ER PT S AU Shire, DB Ellersick, W Kelly, SK Doyle, P Priplata, A Drohan, W Mendoza, O Gingerich, M McKee, B Wyatt, JL Rizzo, JF AF Shire, Douglas B. Ellersick, William Kelly, Shawn K. Doyle, Patrick Priplata, Attila Drohan, William Mendoza, Oscar Gingerich, Marcus McKee, Bruce Wyatt, John L. Rizzo, Joseph F., III GP IEEE TI ASIC Design and Data Communications for the Boston Retinal Prosthesis SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE AB We report on the design and testing of a custom application-specific integrated circuit (ASIC) that has been developed as a key component of the Boston retinal prosthesis. This device has been designed for patients who are blind due to age-related macular degeneration or retinitis pigmentosa. Key safety and communication features of the low-power ASIC are described, as are the highly configurable neural stimulation current waveforms that are delivered to its greater than 256 output electrodes. The ASIC was created using an 0.18 micron Si fabrication process utilizing standard 1.8 volt CMOS transistors as well as 20 volt lightly doped drain FETs. The communication system receives frequency-shift keyed inputs at 6.78 MHz from an implanted secondary coil, and transmits data back to the control unit through a lower-bandwidth channel that employs load-shift keying. The design's safety is ensured by on-board electrode voltage monitoring, stimulus charge limits, error checking of data transmitted to the implant, and comprehensive self-test and performance monitoring features. Each stimulus cycle is initiated by a transmitted word with a full 32-bit error check code. Taken together, these features allow researchers to safely and wirelessly tailor retinal stimulation and vision recovery for each patient. C1 [Shire, Douglas B.; Kelly, Shawn K.; Drohan, William; Gingerich, Marcus; McKee, Bruce] Boston VA Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. [Mendoza, Oscar; Wyatt, John L.] MIT, Cambridge, MA 02139 USA. [Priplata, Attila; Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Doyle, Patrick] Harvest Automat, Billerica 01862, MA USA. RP Shire, DB (reprint author), Boston VA Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM dbs6@cornell.edu OI Kelly, Shawn/0000-0003-3533-5268 NR 9 TC 6 Z9 6 U1 1 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 292 EP 295 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296500072 ER PT S AU Lee, J Boas, DA AF Lee, Jonghwan Boas, David A. GP IEEE TI Frequency-Domain Measurement of Neuronal Activity using Dynamic Optical Coherence Tomography SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE ID ACTION-POTENTIAL PROPAGATION; LIGHT-SCATTERING; NEURAL ACTIVITY; SIGNAL; BIREFRINGENCE; RESPONSES; NERVE AB We report preliminary results on high-resolution in vivo imaging of fast intrinsic optical signals of neuronal activity in the frequency domain. An optical coherence tomography (OCT) system was used for dynamic imaging of the cross section of rodent somatosensory cortex at 250 frame/s. Neurons in the cortex were excited by contralateral forepaw stimulation, and the ipsilateral forepaw was stimulated as a control. Hemodynamic responses at the cortical surface, which were simultaneously measured using a CCD, confirmed that forepaw stimulation properly evoked neuronal activation. Analysis of the OCT signal in the frequency domain resulted in that the spectrum significantly increased at the stimulation frequency during activation. This spectrum change was only observed during contralateral stimulation and highly localized at the stimulation frequency in the frequency space. Therefore, the spectrum change we observed is likely associated with neuronal activation. C1 [Lee, Jonghwan; Boas, David A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biomed Imaging, Boston, MA 02129 USA. RP Lee, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biomed Imaging, Boston, MA 02129 USA. EM jonghwan@nmr.mgh.harvard.edu; dboas@nmr.mgh.harvard.edu NR 16 TC 3 Z9 3 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 2643 EP 2646 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296502215 ER PT S AU Orini, M Citi, L Barbieri, R AF Orini, Michele Citi, Luca Barbieri, Riccardo GP IEEE TI Bivariate point process modeling and joint non-stationary analysis of pulse transit time and heart period SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE ID ARTERIAL-PRESSURE; RATE-VARIABILITY; PHOTOPLETHYSMOGRAPHY AB Pulse transit time (PTT) is strictly related to pulse wave velocity and may be used for non-invasive monitoring of arterial stiffness and pressure, whose assessment is fundamental to detect cardiovascular dysfunctions. We propose a new model to characterize instantaneous PTT dynamics, and the interactions between PTT and R-R interval (RRI). In this model, PTT is described as a point process whose probability function depends on previous PTT and RRI values. From the model coefficients, instantaneous powers, coherence and directed coherence of each spectral component are estimated. We used this framework to study the changes that tilt table test provoked in PTT and RRI dynamics in 17 healthy subjects. Time-varying spectral and coherence analysis revealed that, although PTT and RRI were locally correlated, direct contribution of RRI on PTT was low during the entire test in high frequency band, and just after postural changes in low frequency band. We conclude that PTT may add valuable information for a more accurate characterization of cardiovascular regulation. C1 [Orini, Michele] Univ Zaragoza, IIS Aragon, I3A, GTC, Zaragoza, Spain. RP Citi, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. EM michele@unizar.es; lciti@neurostat.mit.edu; barbieri@neurostat.mit.edu RI Citi, Luca/G-2270-2011; Orini, Michele/H-3937-2015; OI Citi, Luca/0000-0001-8702-5654; Orini, Michele/0000-0001-5773-0344; Barbieri, Riccardo/0000-0001-9381-3833 NR 13 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 2831 EP 2834 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296503015 ER PT S AU Citi, L Valenza, G Purdon, PL Brown, EN Barbieri, R AF Citi, Luca Valenza, Gaetano Purdon, Patrick L. Brown, Emery N. Barbieri, Riccardo GP IEEE TI Monitoring Heartbeat Nonlinear Dynamics during General Anesthesia by using the Instantaneous Dominant Lyapunov Exponent SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE ID RATE-VARIABILITY; TIME-SERIES; IDENTIFICATION; NOCICEPTION; ALGORITHM; SYSTEMS AB We present a novel methodology for instantaneous estimation of quantitative correlates of depth of Anaesthesia from noninvasive electrocardiographic recordings. The analysis is based on a point process model of heartbeat dynamics that allows for continuous tracking of linear and nonlinear HRV indices, including a novel instantaneous assessment of the Lyapunov Spectrum by using a cubic autoregressive formulation. The effective estimation of the model parameters is ensured by the Laguerre expansion of the Wiener-Volterra kernels along with the maximum local log-likelihood procedure. We apply the proposed assessment to experimental recordings from healthy subjects during propofol anesthesia. The new assessment reveals novel time-varying complex heartbeat dynamics that underlie the quasi-periodic heartbeat fluctuations elicited by the sympatho-vagal balance. Results suggest that such quantification provides important information which is independent from the standard autonomic assessment and significantly correlated with loss of consciousness. Further investigation will focus on evolving our mathematical approach towards a promising monitoring tool for an accurate, noninvasive assessment of general anesthesia. C1 [Citi, Luca; Valenza, Gaetano; Purdon, Patrick L.; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Barbieri, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM lciti@neurostat.mit.edu; g.valenza@ieee.org; patrickp@neurostat.mit.edu; enb@neurostat.mit.edu; barbieri@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833; Valenza, Gaetano/0000-0001-6574-1879 NR 21 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 3124 EP 3127 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296503087 ER PT S AU Wang, HW Grindle, GG Candiotti, J Chung, CS Shino, M Houston, E Cooper, RA AF Wang, Hongwu Grindle, Garrett G. Candiotti, Jorge Chung, Chengshiu Shino, Motoki Houston, Elaine Cooper, Rory A. GP IEEE TI The Personal Mobility and Manipulation Appliance (PerMMA): a Robotic Wheelchair with Advanced Mobility and Manipulation SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE ID POWERED MOBILITY AB The Personal Mobility and Manipulation Appliance (PerMMA) is a recently developed personal assistance robot developed to provide people with disabilities and older adults enhanced assistance in both mobility and manipulation, which are two fundamental components for independently activities of daily life performing, community participation, and quality of life. Technologies to assist with mobility and manipulation are among the most important tools for clinicians, end users and caregivers; however, there are currently few systems that provide practical and coordinated assistance with mobility and manipulation tasks. The PerMMA was not only developed and evaluated to provide users and caregivers enhanced mobility and manipulation options, but also as a clinical tool as well as research platform. The development and evaluation of PerMMA are presented in the paper. C1 [Wang, Hongwu; Grindle, Garrett G.; Candiotti, Jorge; Chung, Chengshiu; Houston, Elaine; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. RP Wang, HW (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu RI Wang, Hongwu/J-6133-2013 OI Wang, Hongwu/0000-0002-6567-9144 NR 10 TC 4 Z9 4 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 3324 EP 3327 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296503137 ER PT S AU Cai, WL Kim, SH Lee, JG Yoshida, H AF Cai, Wenli Kim, Se Hyung Lee, June-Goo Yoshida, Hiroyuki GP IEEE TI Virtual Colon Tagging for Electronic Cleansing in Dual-energy Fecal-tagging CT Colonography SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE ID COMPUTED-TOMOGRAPHY AB Partial volume effect (PVE) and tagging inhomogeneity are two major causes of artifacts in electronic cleansing (EC) for fecal-tagging CT colonography (CTC). Our purpose was to develop a novel method called "virtual tagging" for electronic cleansing in dual-energy fecal-tagging CTC. A three-material decomposition scheme was first applied in dual-energy CTC to decompose each voxel into a mixture of air, soft tissue, and iodine-tagged fecal material. The entire colonic lumen was then marked by virtually tagging the mixture portion of luminal air at each voxel. As a result, colon lumen including air and tagged materials was segmented and subtracted by their high values in virtually tagged images. Our virtual tagging scheme provides a cleansed colon that is free from artifacts caused by the PVE at air-tagging mixture and inhomogeneous tagging. C1 [Cai, Wenli; Lee, June-Goo; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM cai.wenli@mgh.harvard.edu; shkim@radcom.snu.ac.kr; lee.june@mgh.harvard.edu; yoshida.hiro@mgh.harvard.edu NR 13 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 3736 EP 3739 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296503239 ER PT S AU Nappi, JJ Kim, SH Yoshida, H AF Naeppi, Janne J. Kim, Se Hyung Yoshida, Hiroyuki GP IEEE TI Volumetric Detection of Colorectal Lesions for Noncathartic Dual-Energy Computed Tomographic Colonography SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE ID FREE CT COLONOGRAPHY; FALSE POSITIVES; POLYPS; REDUCTION AB Noncathartic computed tomographic colonography (CTC) could significantly increase patient adherence to colorectal screening guidelines. However, radiologists find the interpretation of noncathartic CTC images challenging. We developed a fully automated computer-aided detection (CAD) scheme for assisting radiologists with noncathartic CTC. A volumetric method is used to detect lesions within a thick target region encompassing the colonic wall. Dual-energy CTC (DE-CTC) is used to provide more detailed information about the colon than what is possible with conventional CTC. False-positive detections are reduced by use of a random-forest classifier. The effect of the thickness of the target region on detection performance was assessed by use of 22 clinical noncathartic DE-CTC studies including 27 lesions >= 6 mm. The results indicate that the thickness parameter can have significant effect on detection accuracy. Leave-one-patient-out evaluation indicated that the proposed CAD scheme detects colorectal lesions at high accuracy in noncathartic CTC. C1 [Naeppi, Janne J.; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. RP Nappi, JJ (reprint author), Massachusetts Gen Hosp, Dept Imaging, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM jnappi@partners.org; yoshida.hiro@mgh.harvard.edu NR 23 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 3740 EP 3743 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296503240 ER PT S AU Yoshida, H Wu, Y Cai, WL Brett, B AF Yoshida, Hiroyuki Wu, Yin Cai, Wenli Brett, Bevin GP IEEE TI Scalable, High-performance 3D Imaging Software Platform: System Architecture and Application to Virtual Colonoscopy SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE AB One of the key challenges in three-dimensional (3D) medical imaging is to enable the fast turn-around time, which is often required for interactive or real-time response. This inevitably requires not only high computational power but also high memory bandwidth due to the massive amount of data that need to be processed. In this work, we have developed a software platform that is designed to support high-performance 3D medical image processing for a wide range of applications using increasingly available and affordable commodity computing systems: multi-core, clusters, and cloud computing systems. To achieve scalable, high-performance computing, our platform (1) employs size-adaptive, distributable block volumes as a core data structure for efficient parallelization of a wide range of 3D image processing algorithms; (2) supports task scheduling for efficient load distribution and balancing; and (3) consists of a layered parallel software libraries that allow a wide range of medical applications to share the same functionalities. We evaluated the performance of our platform by applying it to an electronic cleansing system in virtual colonoscopy, with initial experimental results showing a 10 times performance improvement on an 8-core workstation over the original sequential implementation of the system. C1 [Yoshida, Hiroyuki; Wu, Yin; Cai, Wenli] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Yoshida, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM yoshida.hiro@mgh.harvard.edu; ywu14@partners.org; cai.wenli@mgh.harvard.edu NR 9 TC 1 Z9 1 U1 1 U2 5 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 3994 EP 3997 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296504054 ER PT S AU Liddle, S Grover, L Zhang, R Khitrov, M Brown, JC Cobb, JP Goldman, J Chou, J Yagoda, D Westover, B Reisner, AT AF Liddle, Stephanie Grover, Lata Zhang, Rachel Khitrov, Maxim Brown, Joan C. Cobb, J. Perren Goldman, Julian Chou, Joseph Yagoda, Daniel Westover, Brandon Reisner, Andrew T. GP IEEE TI Safety Evaluation of a Medical Device Data System SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE AB Our hospital became interested in the extraction of electronic data from our bedside monitor network to enrich clinical care, and enable various quality improvement projects, research projects, and future applications involving advanced decision-support. We conducted a range of tests to confirm the safety of deploying BedMaster (Excel Medical Electronics, Jupiter FL, USA), which is third-party software sold expressly to provide electronic data extraction and storage from networked General Electric Healthcare bedside patient monitors. We conducted a series of tests examining the changes in network performance when the BedMaster system was on our isolated patient monitor network. We found that use of BedMaster led to measurable, but trivial increases in network traffic and latency. We did not identify any failure scenarios in our analysis and testing. The major value of this report is to highlight potential challenges inherent in data and electronic device integration within the healthcare setting. In describing our strategy for testing the BedMaster system, it is our intention to present one testing protocol and to generate thought and discussion in the broader community about what types of problems can arise with inter-operability, and what types of testing are necessary to mitigate against these risks. Standards for inter-operability would surely reduce the inherent risks. C1 [Liddle, Stephanie; Grover, Lata; Zhang, Rachel; Brown, Joan C.; Cobb, J. Perren; Goldman, Julian; Chou, Joseph; Yagoda, Daniel; Westover, Brandon; Reisner, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reisner, AT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM areisner@partners.org NR 3 TC 4 Z9 4 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 5899 EP 5902 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296506025 ER PT S AU Sampson, AL Babadi, B Prerau, MJ Mukamel, EA Brown, EN Purdon, PL AF Sampson, A. L. Babadi, B. Prerau, M. J. Mukamel, E. A. Brown, E. N. Purdon, P. L. GP IEEE TI A Beamforming Approach to Phase-Amplitude Modulation Analysis of Multi-Channel EEG SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE AB Phase-amplitude modulation is a form of cross frequency coupling where the phase of one frequency influences the amplitude of another higher frequency. It has been observed in neurophysiological recordings during sensory, motor, and cognitive tasks, as well as during general anesthesia. In this paper, we describe a novel beamforming procedure to improve estimation of phase-amplitude modulation. We apply this method to 64-channel EEG data recorded during propofol general anesthesia. The method improves the sensitivity of phase-amplitude analyses, and can be applied to a variety of multi-channel neuroscience data where phase-amplitude modulation is present. C1 [Sampson, A. L.; Babadi, B.; Prerau, M. J.; Brown, E. N.; Purdon, P. L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Sampson, AL (reprint author), 149 13th St,Room 4-013, Charlestown, MA 02129 USA. EM asampson@nmr.mgh.harvard.edu; patrickp@nmr.mgh.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 6731 EP 6734 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296506225 ER PT S AU Obregon-Henao, G Babadi, B Lamus, C Brown, EN Purdon, PL AF Obregon-Henao, G. Babadi, B. Lamus, C. Brown, E. N. Purdon, P. L. GP IEEE TI A Fast Iterative Greedy Algorithm for MEG Source Localization SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE ID SURFACE-BASED ANALYSIS; INVERSE PROBLEM; RECONSTRUCTION; MAGNETOENCEPHALOGRAPHY; BRAIN; MODEL; EEG AB Recent dynamic source localization algorithms for the Magnetoencephalographic inverse problem use cortical spatio-temporal dynamics to enhance the quality of the estimation. However, these methods suffer from high computational complexity due to the large number of sources that must be estimated. In this work, we introduce a fast iterative greedy algorithm incorporating the class of subspace pursuit algorithms for sparse source localization. The algorithm employs a reduced order state-space model resulting in significant computational savings. Simulation studies on MEG source localization reveal substantial gains provided by the proposed method over the widely used minimum-norm estimate, in terms of localization accuracy, with a negligible increase in computational complexity. C1 [Obregon-Henao, G.; Babadi, B.; Lamus, C.; Brown, E. N.; Purdon, P. L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Obregon-Henao, G (reprint author), 149 13th St,Room 4-013, Charlestown, MA 02129 USA. EM obregon@nmr.mgh.harvard.edu; patrickp@nmr.mgh.harvard.edu NR 16 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 6748 EP 6751 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296506229 ER PT S AU Pirondini, E Babadi, B Lamus, C Brown, EN Purdon, PL AF Pirondini, E. Babadi, B. Lamus, C. Brown, E. N. Purdon, P. L. GP IEEE TI A Spatially-Regularized Dynamic Source Localization Algorithm for EEG SO 2012 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 34th Annual International Conference of the IEEE Engineering-in-Medicine-and-Biology-Society (EMBS) CY AUG 28-SEP 01, 2012 CL San Diego, CA SP IEEE, Engn Med & Biol Soc (EMBS), CAS, SMC, PubMed, MEDLINE ID INVERSE PROBLEM AB Cortical activity can be estimated from electroencephalogram (EEG) or magnetoencephalogram (MEG) data by solving an ill-conditioned inverse problem that is regularized using neuroanatomical, computational, and dynamic constraints. Recent methods have incorporated spatio-temporal dynamics into the inverse problem framework. In this approach, spatio-temporal interactions between neighboring sources enforce a form of spatial smoothing that enhances source localization quality. However, spatial smoothing could also occur by way of correlations within the state noise process that drives the underlying dynamic model. Estimating the spatial covariance structure of this state noise is challenging, particularly in EEG and MEG data where the number of underlying sources is far greater than the number of sensors. However, the EEG/MEG data are sparse compared to the large number of sources, and thus sparse constraints could be used to simplify the form of the state noise spatial covariance. In this work, we introduce an empirically tailored basis to represent the spatial covariance structure within the state noise processes of a cortical dynamic model for EEG source localization. We augment the method presented in Lamus, et al. (2011) to allow for sparsity enforcing priors on the covariance parameters. Simulation studies as well as analysis of real data reveal significant gains in the source localization performance over existing algorithms. C1 [Pirondini, E.; Babadi, B.; Lamus, C.; Brown, E. N.; Purdon, P. L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Pirondini, E (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM elvira.pirondini@epfl.ch; patrickp@nmr.mgh.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-1787-1 J9 IEEE ENG MED BIO PY 2012 BP 6752 EP 6755 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BDH78 UT WOS:000313296506230 ER PT J AU Brady, KT Back, SE AF Brady, Kathleen T. Back, Sudie E. TI Childhood Trauma, Posttraumatic Stress Disorder, and Alcohol Dependence SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Article DE Alcohol dependence; alcohol use disorders; childhood; childhood trauma; trauma-related symptoms; posttraumatic stress disorder; coping with stress or anxiety; neurobiology; biological mechanisms; treatment; pharmacological intervention; behavioral intervention; integrative psychosocial intervention; adverse child-rearing environment ID SUBSTANCE USE DISORDERS; COOCCURRING PTSD; MATERNAL-CARE; ABUSE; EXPERIENCES; THERAPY; SYSTEMS; WOMEN; TRIAL; VICTIMIZATION AB Early-childhood trauma is strongly associated with developing mental health problems, including alcohol dependence, later in life. People with early-life trauma may use alcohol to help cope with trauma-related symptoms. This article reviews the prevalence of early-childhood trauma and its robust association with the development of alcohol use disorders and posttraumatic stress disorder. It also examines the potential biological mechanisms by which early adverse experiences can result in long-lasting changes in neurobiology underlying this vulnerability, as well as pharmacological and behavioral interventions. Recent investigations highlight the importance of assessing trauma among patients with alcohol use disorders and the positive benefits associated with the application of integrative psychosocial interventions that target both trauma-related symptoms and alcohol dependence. C1 [Brady, Kathleen T.] Med Univ S Carolina, Clin Neurosci Div, Charleston, SC 29425 USA. [Brady, Kathleen T.; Back, Sudie E.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Brady, KT (reprint author), Med Univ S Carolina, Clin Neurosci Div, Charleston, SC 29425 USA. FU NIDA NIH HHS [K24 DA-00435, K23 DA-021228] NR 52 TC 11 Z9 11 U1 1 U2 21 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2012 VL 34 IS 4 BP 408 EP 413 PG 6 WC Substance Abuse SC Substance Abuse GA 066QB UT WOS:000313234200005 PM 23584107 ER PT J AU Becker, HC AF Becker, Howard C. TI Effects of Alcohol Dependence and Withdrawal on Stress Responsiveness and Alcohol Consumption SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Article DE Alcohol consumption; alcohol dependence; chronic alcohol exposure; drinking behavior; withdrawal; relapse; stress; stress response; biological adaptation to stress; brain; brain stress pathway; hypothalamic-pituitary-adrenocortical axis; corticotropin-releasing factor; corticosteroids; norepinephrine; human studies; animal models ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; CHRONIC ETHANOL EXPOSURE; ANXIETY-LIKE BEHAVIOR; INCREASES ALLOPREGNANOLONE LEVELS; RECEPTOR ANTAGONIST ANTALARMIN; AMINOBUTYRIC-ACID RELEASE; NEUROACTIVE STEROIDS; VOLUNTARY ETHANOL; C57BL/6J MICE AB A complex relationship exists between alcohol-drinking behavior and stress. Alcohol has anxiety-reducing properties and can relieve stress, while at the same time acting as a stressor and activating the body's stress response systems. In particular, chronic alcohol exposure and withdrawal can profoundly disturb the function of the body's neuroendocrine stress response system, the hypothalamic-pituitary-adrenocortical (HPA) axis. A hormone, corticotropin-releasing factor (CRF), which is produced and released from the hypothalamus and activates the pituitary in response to stress, plays a central role in the relationship between stress and alcohol dependence and withdrawal. Chronic alcohol exposure and withdrawal lead to changes in CRF activity both within the HPA axis and in extrahypothalamic brain sites. This may mediate the emergence of certain withdrawal symptoms, which in turn influence the susceptibility to relapse. Alcohol-related dysregulation of the HPA axis and altered CRF activity within brain stress reward circuitry also may play a role in the escalation of alcohol consumption in alcohol-dependent individuals. Numerous mechanisms have been suggested to contribute to the relationship between alcohol dependence, stress, and drinking behavior. These include the stress hormones released by the adrenal glands in response to HPA axis activation (i.e., corticosteroids), neuromodulators known as neuroactive steroids, CRF, the neurotransmitter norepinephrine, and other stress-related molecules. C1 [Becker, Howard C.] Med Univ S Carolina, Dept Neurosci, Dept Psychiat & Behav Sci, Charleston Alcohol Res Ctr, Charleston, SC 29425 USA. [Becker, Howard C.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Becker, HC (reprint author), Med Univ S Carolina, Dept Neurosci, Dept Psychiat & Behav Sci, Charleston Alcohol Res Ctr, Charleston, SC 29425 USA. FU BLRD VA [I01 BX000813]; NIAAA NIH HHS [P50 AA010761, R01 AA018036, U01 AA014095, U01 AA020929] NR 151 TC 33 Z9 34 U1 1 U2 17 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2012 VL 34 IS 4 BP 448 EP 458 PG 11 WC Substance Abuse SC Substance Abuse GA 066QB UT WOS:000313234200009 PM 23584111 ER PT J AU DeGutis, J Chatterjee, G Mercado, RJ Nakayama, K AF DeGutis, Joseph Chatterjee, Garga Mercado, Rogelio J. Nakayama, Ken TI Face gender recognition in developmental prosopagnosia: Evidence for holistic processing and use of configural information SO VISUAL COGNITION LA English DT Article DE Developmental prosopagnosia; Face inversion; Gender recognition; Holistic processing ID PERCEPTION; MECHANISMS; IDENTITY; FAMILIAR; SEX AB Face identification deficits in developmental prosopagnosics (DPs) have been thought to be due to general difficulties with processing configural face information and integrating configural and parts information into a coherent whole (holistic processing). Gender recognition provides a further opportunity to more fully examine this issue as this ability may be intact in DPs and it has been shown to depend on processing configural information and holistic processing in neurotypical individuals. In the present study we first determined that, indeed, gender discrimination performance was similar in DPs and controls. Second, we found that inversion and scrambling (which we propose measures holistic processing and sensitivity to configural information, respectively) produced comparable deficits in DPs and controls, suggesting that both groups use holistic processing and configural information to recognize gender. This indicates that holistic processing and using configural face information are not general impairments in DP and may be more specific to face identity. C1 [DeGutis, Joseph; Mercado, Rogelio J.] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Jamaica Plain, MA USA. [DeGutis, Joseph; Chatterjee, Garga; Mercado, Rogelio J.; Nakayama, Ken] Harvard Univ, Dept Psychol, Vis Sci Lab, Cambridge, MA 02138 USA. RP DeGutis, J (reprint author), VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA 02130 USA. EM degutis@wjh.harvard.edu NR 27 TC 10 Z9 10 U1 2 U2 12 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1350-6285 J9 VIS COGN JI Vis. Cogn. PY 2012 VL 20 IS 10 BP 1242 EP 1253 DI 10.1080/13506285.2012.744788 PG 12 WC Psychology, Experimental SC Psychology GA 073YL UT WOS:000313778900007 ER PT S AU Mansour, MK Tam, JM Vyas, JM AF Mansour, Michael K. Tam, Jenny M. Vyas, Jatin M. BE Clemons, KV Perlin, DS Richardson, M TI The cell biology of the innate immune response to Aspergillus fumigatus SO ADVANCES AGAINST ASPERGILLOSIS II SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 5th Advances Against Aspergillosis Conference CY JAN 26-28, 2012 CL Istanbul, TURKEY DE innate immunity; Dectin-1; Toll-like receptor; phagosome; macrophage; TLR9 ID TOLL-LIKE RECEPTORS; C-TYPE LECTINS; DENDRITIC CELLS; FUNGAL-INFECTIONS; PROTEOLYTIC CLEAVAGE; ANTIFUNGAL IMMUNITY; CANDIDA-ALBICANS; DECTIN-1; ACTIVATION; MACROPHAGES AB The development of invasive aspergillosis is a feared complication for immunocompromised patients. Despite the use of antifungal agents with excellent bioactivity, the morbidity and mortality rates for invasive aspergillosis remain unacceptably high. Defects within the innate immune response portend the highest risk for patients, but detailed knowledge of molecular pathways in neutrophils and macrophages in response to this fungal pathogen is lacking. Phagocytosis of fungal spores is a key step that places the pathogen into a phagosome, a membrane-delimited compartment that undergoes maturation and ultimately delivers antigenic material to the class II MHC pathway. We review the role of Toll-like receptor 9 (TLR9) in phagosome maturation of Aspergillus fumigates-containing phagosomes. Advanced imaging modalities and the development of fungal-like particles are promising tools that will aid in the dissection of the molecular mechanism to fungal immunity. C1 [Mansour, Michael K.; Tam, Jenny M.; Vyas, Jatin M.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Mansour, Michael K.; Tam, Jenny M.; Vyas, Jatin M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Vyas, Jatin M.] Harvard Univ, Sch Med, Program Immunol, Boston, MA USA. RP Vyas, JM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, 55 Fruit St,Gray Jackson Bldg,Room 504, Boston, MA 02114 USA. EM jvyas@partners.org RI Vyas, Jatin/Q-1627-2016 OI Vyas, Jatin/0000-0002-9985-9565 FU NIH [R01 AI092084, T32AI007061] FX J.M.V. and J.M.T. are supported by NIH Grant R01 AI092084. M. K. M. is supported by NIH Grant T32AI007061. The authors thank all of the current and former members of the laboratory. NR 51 TC 8 Z9 8 U1 0 U2 8 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-915-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1273 BP 78 EP 84 DI 10.1111/j.1749-6632.2012.06837.x PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental; Multidisciplinary Sciences; Mycology SC Biochemistry & Molecular Biology; Research & Experimental Medicine; Science & Technology - Other Topics; Mycology GA BDB78 UT WOS:000312500200012 PM 23230841 ER PT J AU Kopans, DB AF Kopans, Daniel B. TI Do not jump too quickly to conclusions SO BREAST CANCER RESEARCH LA English DT Editorial Material ID BREAST-CANCER; MAMMOGRAPHY; TRIALS; OVERDIAGNOSIS; BENEFITS; IMPACT; WOMEN; AGE AB A great deal of misinformation has been promulgated about mammography screening. For example, there is no biological or scientific support for the use of the age of 50 years as a threshold for screening. Mammography screening can reduce deaths from breast cancer even if the rate of advanced cancers is not decreased. The suggestion that screening results in massive amounts of overdiagnosis is based upon faulty methodology. The results reported in the recent study by Nederend and colleagues may be due to the screening interval and thresholds used for intervention. What is clear, however, is that they do not show that screening is ineffective. C1 [Kopans, Daniel B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kopans, Daniel B.] Massachusetts Gen Hosp, Dept Radiol, Breast Imaging Div, Avon Comprehens Breast Ctr, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Harvard Univ, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. EM dkopans@partners.org NR 19 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 4 AR 108 DI 10.1186/bcr3213 PG 2 WC Oncology SC Oncology GA 065ZP UT WOS:000313189600027 PM 22824314 ER PT J AU Vaz-Luis, I Ottesen, RA Hughes, ME Marcom, PK Moy, B Rugo, HS Theriault, RL Wilson, J Niland, JC Weeks, JC Lin, NU AF Vaz-Luis, Ines Ottesen, Rebecca A. Hughes, Melissa E. Marcom, P. Kelly Moy, Beverly Rugo, Hope S. Theriault, Richard L. Wilson, John Niland, Joyce C. Weeks, Jane C. Lin, Nancy U. TI Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study SO BREAST CANCER RESEARCH LA English DT Article ID NERVOUS-SYSTEM METASTASES; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; MOLECULAR PORTRAITS; PRIMARY THERAPY; TRASTUZUMAB; EXPRESSION; PACLITAXEL; ESTROGEN; GENES AB Introduction: In gene expression experiments, hormone receptor (HR)-positive/human epidermal growth factor-2 (HER2)-positive tumors generally cluster within the luminal B subset; whereas HR-negative/HER2-positive tumors reside in the HER2-enriched subset. We investigated whether the clinical behavior of HER2-positive tumors differs by HR status. Methods: We evaluated 3,394 patients who presented to National Comprehensive Cancer Network (NCCN) centers with stage I to III HER2-positive breast cancer between 2000 and 2007. Tumors were grouped as HR-positive/HER2-positive (HR+/HER2+) or HR-negative/HER2-positive (HR-/HER2+). Chi-square, logistic regression and Cox hazard proportional regression were used to compare groups. Results: Median follow-up was four years. Patients with HR-/HER2+ tumors (n = 1,379, 41% of total) were more likely than those with HR+/HER-2+ disease (n = 2,015, 59% of total) to present with high histologic grade and higher stages (P < 0.001). Recurrences were recorded for 458 patients. HR-/HER2+ patients were less likely to experience first recurrence in bone (univariate Odds Ratio (OR) = 0.53, 95% Confidence Interval (CI): 0.34 to 0.82, P = 0.005) and more likely to recur in brain (univariate OR = 1.75, 95% CI: 1.05 to 2.93, P = 0.033). A lower risk of recurrence in bone persisted after adjusting for age, stage and adjuvant trastuzumab therapy (OR = 0.53, 95% CI: 0.34 to 0.83, P = 0.005) and when first and subsequent sites of recurrence were both considered (multivariable OR = 0.55, 95% CI: 0.37 to 0.80, P = 0.002). As compared with patients with HR+/HER2+ disease, those with HR-/HER2+ disease had significantly increased hazard of early, but not late, death (hazard ratio of death zero to two years after diagnosis = 1.92, 95% CI: 1.28 to 2.86, P = 0.002, hazard ratio of death two to five years after diagnosis = 1.55, 95% CI: 1.19 to 2.00, P = 0.001; hazard ratio of death more than five years after diagnosis = 0.81, 95% CI: 0.55 to 1.19, P = 0.285, adjusting for age, race/ethnicity, stage at diagnosis, grade and year of diagnosis). Conclusions: Presenting features, patterns of recurrence and survival of HER2-positive breast cancer differed by HR status. These differences should be further explored and integrated in the design of clinical trials. C1 [Vaz-Luis, Ines; Hughes, Melissa E.; Weeks, Jane C.; Lin, Nancy U.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Vaz-Luis, Ines] Inst Mol Med, Clin & Translat Oncol Res Unit, Lisbon, Portugal. [Ottesen, Rebecca A.; Niland, Joyce C.] City Hope Comprehens Canc Ctr, Dept Informat Sci, Duarte, CA USA. [Marcom, P. Kelly] Duke Univ, Med Ctr, Dept Med Oncol, Durham, NC USA. [Moy, Beverly] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rugo, Hope S.] San Francisco Helen Diller Family Comprehens Canc, Dept Med, San Francisco, CA USA. [Theriault, Richard L.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Wilson, John] Ohio State Univ, Dept Internal Med, Arthur G James Canc Hosp, Columbus, OH 43210 USA. RP Vaz-Luis, I (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM inesV_Luis@dfci.harvard.edu FU National Cancer Institute Specialized Program of Research Excellence in Breast Cancer [NIH P50 CA089393]; National Comprehensive Cancer Network; Breast Cancer Research Foundation; Karen Webster and David Evans Research Fund; Scholars in Clinical Science Program of Harvard Catalyst \ The Harvard Clinical and Translational Science Center [UL1 RR025758]; Harvard University; FCT [HMSP-ICS/0004/2011]; American Society of Clinical Oncology Cancer Foundation; Berry Junior Faculty Award; Genentech; GlaxoSmithKline; Infinity Pharmaceuticals; Boehringer Ingelheim; Novartis FX The authors acknowledge the National Cancer Institute Specialized Program of Research Excellence in Breast Cancer (NIH P50 CA089393); National Comprehensive Cancer Network; Breast Cancer Research Foundation; Karen Webster and David Evans Research Fund. This work was conducted with the support from the Scholars in Clinical Science Program of Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (Award No. UL1 RR025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. IVL is supported by FCT (HMSP-ICS/0004/2011). The study was supported by the National Cancer Institute Specialized Program of Research Excellence in Breast Cancer (NIH P50 CA089393), the National Comprehensive Cancer Network, Breast Cancer Research Foundation (to NUL), American Society of Clinical Oncology Cancer Foundation (Career Development Award to NUL), Berry Junior Faculty Award (to NUL), and the Karen Webster and David Evans Research Fund.; BM is an uncompensated consultant or has an uncompensated advisory role for GlaxoSmithKline and Pfizer. RLT has stock ownership in UpToDate, NUL receives Research Funding from Genentech, GlaxoSmithKline, Infinity Pharmaceuticals, Boehringer Ingelheim, and has a consultant or advisory role for GlaxoSmithKline (compensated), Novartis (compensated) and Genentech (uncompensated). IVL, RAO, MEH, PKM, HSR, JW, JCN and JCW declare that they have no competing interests. NR 52 TC 42 Z9 43 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 5 AR R129 DI 10.1186/bcr3324 PG 14 WC Oncology SC Oncology GA 066AQ UT WOS:000313192400017 PM 23025714 ER PT J AU Albright, KC Savitz, SI Raman, R Martin-Schild, S Broderick, J Ernstrom, K Ford, A Khatri, R Kleindorfer, D Liebeskind, D Marshall, R Merino, JG Meyer, DM Rost, N Meyer, BC AF Albright, Karen C. Savitz, Sean I. Raman, Rema Martin-Schild, Sheryl Broderick, Joseph Ernstrom, Karin Ford, Andria Khatri, Rakesh Kleindorfer, Dawn Liebeskind, David Marshall, Randolph Merino, Jose G. Meyer, Dawn M. Rost, Natalia Meyer, Brett C. CA SPOTRIAS Investigators TI Comprehensive Stroke Centers and the 'Weekend Effect': The SPOTRIAS Experience SO CEREBROVASCULAR DISEASES LA English DT Article DE The 'weekend effect'; Acute stroke; Organized stroke care ID CASE-FATALITY; WEEKDAY ADMISSION; MORTALITY; LENGTH; IMPACT; UNITS; STAY; TIME AB Background and Purpose: Previous studies have found mortality among ischemic stroke patients to be higher on weekends. We sought to evaluate whether weekend admission was associated with worse outcomes in a large comprehensive stroke center (CSC) cohort. Methods: Consecutive ischemic stroke patients presenting within 6 h of symptom onset were identified using the 8 CSC SPOTRIAS (Specialized Programs of Translational Research in Acute Stroke) database. Patients who received intra-arterial therapy or who were enrolled in a nonobservational clinical trial were excluded. All patients meeting the inclusion criteria were then divided into two groups: weekday admissions or weekend admissions. Weekend admission was defined as Friday 17: 01 to Monday 08:59. The remainder were classified as weekday admissions. Multivariate logistic regression was used, adjusting for age, stroke severity on admission [according to the National Institutes of Health Stroke Scale (NIHSS)] and admission glucose, in order to compare the outcomes of the weekend versus the weekday groups. Results: Eight thousand five hundred and eighty-one subjects from the combined SPOTRIAS database were screened from 2002 to 2009; 2,090 (24.4%) of these met the inclusion criteria. There was no significant difference in tissue plasminogen activator treatment rates between the weekday and weekend groups (58.5 vs. 60.4%, p = 0.397). Weekend admission was not a significant independent predictor of inhospital mortality (8.4 vs. 9.9%, p = 0.056), length of stay (4 vs. 5 days, p = 0.442), favorable discharge disposition (38.0 vs. 42.2%, p = 0.122), favorable functional outcome at discharge (41.6 vs. 43.4%, p = 0.805), favorable 90-day functional outcome (54.2 vs. 46.9%, p = 0.301), or 90-day mortality (18.2 vs. 19.8%, p = 0.680) when adjusting for age, NIHSS and admission glucose. Conclusions: In this large cohort of ischemic stroke patients treated at CSCs, we did not observe the 'weekend effect.' This may be due to access to stroke specialists 24 h a day on 365 days a year, nurses with stroke experience and the organized system for delivering care that is available at CSCs. These results suggest that EMS protocol should be reexamined regarding the preferential delivery of weekend stroke victims to hospitals that provide all levels of reperfusion therapy. This further highlights the importance of organized stroke care. Copyright (C) 2012 S. Karger AG, Basel C1 [Albright, Karen C.] Univ Alabama Birmingham, Hlth Serv, Birmingham, AL USA. [Albright, Karen C.] Univ Alabama Birmingham, Ctr Outcome & Effectiveness Res & Educ, Birmingham, AL USA. [Albright, Karen C.] Univ Alabama Birmingham, Ctr Excellence Comparat Effectiveness Res Elimina, Minor Hlth & Hlth Dispar Res Ctr, Birmingham, AL USA. [Albright, Karen C.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. [Albright, Karen C.] Univ Alabama Birmingham, Dept Neurol, Sch Med, Birmingham, AL 35294 USA. [Savitz, Sean I.] Univ Texas Houston, Dept Neurol, Houston, TX USA. [Raman, Rema; Ernstrom, Karin] Univ Calif San Diego, Div Biostat & Bioinformat, Dept Family & Prevent Med, San Diego, CA USA. [Meyer, Dawn M.; Meyer, Brett C.] Univ Calif San Diego, Dept Neurosci, San Diego, CA USA. [Martin-Schild, Sheryl] Tulane Univ, Sch Med, Dept Neurol, New Orleans, LA 70112 USA. [Broderick, Joseph; Khatri, Rakesh; Kleindorfer, Dawn] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA. [Ford, Andria] Washington Univ, Sch Med, Dept Neurol, Cerebrovasc Dis Sect, St Louis, MO 63110 USA. [Liebeskind, David] Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. [Marshall, Randolph] Columbia Univ, Med Ctr, New York, NY USA. [Merino, Jose G.] Natl Inst Neurol Disorders & Stroke, Sect Stroke Diag & Therapeut, NIH, Bethesda, MD USA. [Rost, Natalia] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. RP Albright, KC (reprint author), RWUH M226,619 19th St S, Birmingham, AL 35249 USA. EM kca@uab.edu FU Intramural Research Program of the NINDS, NIH; Agency for Healthcare Research and Quality (AHRQ) [5 T32 HS013852-10]; National Institute on Minority Health and Health Disparities, NIH [3 P60 MD000502-08S1]; [P50 NS044227] FX The authors would like to thank Patrick D. Lyden, MD, for his invaluable assistance with study design, interpretation of data and critical revision of the manuscript and Sharyl Martini, MD, PhD for her support and assistance. The study was supported by P50 NS044227. The research was supported, in part, by the Intramural Research Program of the NINDS, NIH as well as by Award Nos. 5 T32 HS013852-10 from The Agency for Healthcare Research and Quality (AHRQ) and 3 P60 MD000502-08S1 from The National Institute on Minority Health and Health Disparities, NIH. The content is solely the responsibility of the authors and does not necessarily represent the official views of the AHRQ or the NIH. NR 21 TC 24 Z9 24 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2012 VL 34 IS 5-6 BP 424 EP 429 DI 10.1159/000345077 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 072GA UT WOS:000313656300014 PM 23207423 ER PT J AU Coppadoro, A Bittner, E Berra, L AF Coppadoro, Andrea Bittner, Edward Berra, Lorenzo TI Novel preventive strategies for ventilator-associated pneumonia SO CRITICAL CARE LA English DT Review ID SUBGLOTTIC SECRETION DRAINAGE; ENDOTRACHEAL CUFF PRESSURE; CRITICALLY-ILL PATIENTS; NOSOCOMIAL PNEUMONIA; MECHANICAL VENTILATION; ORAL DECONTAMINATION; POLYURETHANE CUFF; RANDOMIZED-TRIAL; GASTRIC CONTENTS; BODY POSITION C1 [Coppadoro, Andrea] Osped San Gerardo, Dept Anesthesiol & Intens Care, I-20052 Monza, Italy. [Bittner, Edward; Berra, Lorenzo] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Coppadoro, A (reprint author), Osped San Gerardo, Dept Anesthesiol & Intens Care, Via Pergolesi 33, I-20052 Monza, Italy. EM andrea.coppadoro@gmail.com NR 47 TC 9 Z9 10 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2012 VL 16 IS 2 AR 210 DI 10.1186/cc11225 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 066CF UT WOS:000313196800050 PM 22429668 ER PT J AU Nelson, J Billeter, AT Seifert, B Neuhaus, V Trentz, O Hofer, CK Turina, M AF Nelson, Jana Billeter, Adrian T. Seifert, Burkhardt Neuhaus, Valentin Trentz, Otmar Hofer, Christoph K. Turina, Matthias TI Obese trauma patients are at increased risk of early hypovolemic shock: a retrospective cohort analysis of 1,084 severely injured patients SO CRITICAL CARE LA English DT Article ID SEVERE BLUNT TRAUMA; BODY-MASS INDEX; ORGAN FAILURE; MORTALITY; OUTCOMES; IMPACT AB Introduction: Morbid obesity and its consequences are considered risk factors for adverse outcome in trauma, although the pathophysiologic mechanisms are incompletely understood. The aim of this study was to compare initial resuscitation, treatment, and short-term outcome of severely injured patients by body mass index (BMI). Methods: A total of 1,084 severely injured patients with an injury severity score of 16 or greater were enrolled between 1996 and 2009 and grouped according to BMI. Their course of treatment and in-hospital outcome were analyzed by univariate and multivariate comparison. Results: Of these patients, 603 (55.6%) were of normal weight with a BMI between 18.5 and 24.9, 361 (33.3%) had BMI values between 25 and 29.9, and 90 patients (8.3%) were obese (BMI >= 30). Thirty patients (2.8%) had BMI levels below 18.5. All groups were comparable with respect to injury severity, initial resuscitation, and time to ICU admission. There was a tendency towards higher mortality in obese patients (mortality 24.4%) and also overweight patients (mortality 18.8%) when compared with patients with a normal BMI (mortality 16.6%). Obese patients showed the highest mortality on day 0 (8.9% vs. 2.8% in the normal-weight group, P = 0.023), mostly due to persistent shock (6.7%). When corrected for BMI, obese patients are provided significantly lower volumes of intravenous fluids during the initial resuscitation period. Conclusion: In contrast to the mostly American literature, only a low percentage of trauma patients at a European trauma center are obese. These patients are at risk of higher mortality from persistent hemorrhagic shock in the initial phase after trauma, which may potentially be related to relative hypovolemia during the resuscitation period. In the later course of treatment, no significant differences exist with respect to specific complications, hospital stay, or in-hospital mortality. C1 [Nelson, Jana; Trentz, Otmar] Univ Zurich Hosp, Dept Trauma Surg, CH-8091 Zurich, Switzerland. [Billeter, Adrian T.] Univ Louisville Hosp, Price Inst Surg Res, Louisville, KY 40201 USA. [Seifert, Burkhardt] Univ Zurich, Inst Social & Prevent Med, Div Biostat, CH-8001 Zurich, Switzerland. [Neuhaus, Valentin] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Hofer, Christoph K.] Stadtspital Triemli Zurich, Dept Anesthesiol, CH-8063 Zurich, Switzerland. [Turina, Matthias] Cleveland Clin, Dept Colorectal Surg, Cleveland, OH 44195 USA. RP Turina, M (reprint author), Cleveland Clin, Dept Colorectal Surg, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM mturina73@hotmail.com OI Seifert, Burkhardt/0000-0002-5829-2478; Billeter, Adrian/0000-0001-8724-4793; Neuhaus, Valentin/0000-0003-4012-5628 NR 22 TC 19 Z9 19 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2012 VL 16 IS 3 AR R77 DI 10.1186/cc11334 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 066CM UT WOS:000313197500007 PM 22568946 ER PT J AU Zilinski, JL Shah, RV Gaggin, HK Gantzer, ML Wang, TJ Januzzi, JL AF Zilinski, Jodi L. Shah, Ravi V. Gaggin, Hanna K. Gantzer, Mary Lou Wang, Thomas J. Januzzi, James L., Jr. TI Measurement of multiple biomarkers in advanced stage heart failure patients treated with pulmonary artery catheter guided therapy SO CRITICAL CARE LA English DT Article ID RECEPTOR FAMILY-MEMBER; NATRIURETIC PEPTIDE; ANGIOTENSIN-II; ESCAPE TRIAL; SOLUBLE ST2; MORTALITY; HYPONATREMIA; PLASMA; RISK; TROPONIN AB Introduction: This study was carried out to investigate the prognostic utility of biomarkers in advanced stage heart failure (HF) patients requiring ICU admission for pulmonary artery catheter (PAC) guided therapy. Methods: Thirty patients admitted to an ICU for PAC guided HF therapy were enrolled; concentrations of soluble ST2 (sST2), highly sensitive troponin I, an experimental ultrasensitive troponin I, amino-terminal pro-B type natriuretic peptide, cystatin C, and myeloperoxidase were measured over the first 48 hours. Outcomes included response of filling pressures and hemodynamics to tailored therapy and 90-day event-free survival (death, left ventricular assist device implantation, transplant). Results: Of the biomarkers evaluated, only sST2 concentrations were higher in those who failed to achieve goals for central venous pressure ((CVP), 225.3 versus 104.6 ng/mL; P = 0.003) and pulmonary capillary wedge pressure ((PCWP), 181.7 versus 88.2 ng/mL; P = 0.05). Only sST2 concentrations were associated with adverse events (186.7 versus 92.2 ng/mL; P = 0.01). In age-adjusted Cox proportional hazards analysis, an elevated sST2 during the first 48 hours following ICU admission independently predicted 90-day outcomes (Hazard Ratio = 5.53; P = 0.03) superior to the Simplified Acute Physiology Score for this application; in Kaplan-Meier analysis the risk associated with elevated sST2 concentrations was present early and sustained through the duration of follow-up (log rank P = 0.01). Conclusions: In patients undergoing HF therapy guided by invasive monitoring, sST2 concentrations were associated with impending failure to reduce filling pressures and predicted impending events. Elevated sST2 values early in the ICU course theoretically could assist therapeutic decision-making in advanced stage HF patients. C1 [Zilinski, Jodi L.; Shah, Ravi V.; Gaggin, Hanna K.; Wang, Thomas J.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Gantzer, Mary Lou] Siemens Healthcare Diagnost, Newark, DE 19702 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org FU Siemens Diagnostics; Critical Diagnostics; Balson Cardiac Scholar fund; Dennis and Marilyn Barry Fellowship program; Roche Diagnostics; Thermo-Fisher Diagnostics; Diasorin; LabCorp FX Supported in part by an unrestricted grant from Siemens Diagnostics and Critical Diagnostics. Siemens Diagnostics performed measurement of NT-proBNP, hsTnI, eTnI, cys-C and MPO, while Critical Diagnostics performed the sST2 measurement. The authors wish to thank the staff of the Cardiac Intensive Care Unit at the Massachusetts General Hospital for their support of this study. Dr. Januzzi is supported in part by the Balson Cardiac Scholar fund, while Dr. Gaggin is supported by the Dennis and Marilyn Barry Fellowship program.; Dr. Januzzi has received grant support and consulting income from Roche Diagnostics, Siemens Diagnostics, Critical Diagnostics, and Thermo-Fisher Diagnostics. Dr. Wang has received assay or grant support from Diasorin, LabCorp, Siemens Diagnostics, Critical Diagnostics, Thermo-Fisher Diagnostics and honoraria from Quest Diagnostics, Diasorin, and Roche Diagnostics. Dr. Wang is named as a co-inventor on patents relating to the use of metabolite and neurohormonal biomarkers in cardiometabolic risk prediction. Dr. Gantzer was an employee of Siemens. The remaining authors declare that they have no competing interests. NR 33 TC 14 Z9 15 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2012 VL 16 IS 4 AR R135 DI 10.1186/cc11440 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 066CP UT WOS:000313197800022 PM 22830581 ER PT J AU Morgan, XC Tickle, TL Sokol, H Gevers, D Devaney, KL Ward, DV Reyes, JA Shah, SA LeLeiko, N Snapper, SB Bousvaros, A Korzenik, J Sands, BE Xavier, RJ Huttenhower, C AF Morgan, Xochitl C. Tickle, Timothy L. Sokol, Harry Gevers, Dirk Devaney, Kathryn L. Ward, Doyle V. Reyes, Joshua A. Shah, Samir A. LeLeiko, Neal Snapper, Scott B. Bousvaros, Athos Korzenik, Joshua Sands, Bruce E. Xavier, Ramnik J. Huttenhower, Curtis TI Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment SO GENOME BIOLOGY LA English DT Article ID SEGMENTED FILAMENTOUS BACTERIA; INVASIVE ESCHERICHIA-COLI; HUMAN GUT MICROBIOME; CHAIN FATTY-ACIDS; CROHNS-DISEASE; ULCERATIVE-COLITIS; SUSCEPTIBILITY LOCI; HUMAN FECES; FAECALIBACTERIUM-PRAUSNITZII; FECAL MICROBIOTA AB Background: The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis result from alterations in intestinal microbes and the immune system. However, the precise dysfunctions of microbial metabolism in the gastrointestinal microbiome during IBD remain unclear. We analyzed the microbiota of intestinal biopsies and stool samples from 231 IBD and healthy subjects by 16S gene pyrosequencing and followed up a subset using shotgun metagenomics. Gene and pathway composition were assessed, based on 16S data from phylogenetically-related reference genomes, and associated using sparse multivariate linear modeling with medications, environmental factors, and IBD status. Results: Firmicutes and Enterobacteriaceae abundances were associated with disease status as expected, but also with treatment and subject characteristics. Microbial function, though, was more consistently perturbed than composition, with 12% of analyzed pathways changed compared with 2% of genera. We identified major shifts in oxidative stress pathways, as well as decreased carbohydrate metabolism and amino acid biosynthesis in favor of nutrient transport and uptake. The microbiome of ileal Crohn's disease was notable for increases in virulence and secretion pathways. Conclusions: This inferred functional metagenomic information provides the first insights into community-wide microbial processes and pathways that underpin IBD pathogenesis. C1 [Morgan, Xochitl C.; Tickle, Timothy L.; Reyes, Joshua A.; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Tickle, Timothy L.; Gevers, Dirk; Ward, Doyle V.; Xavier, Ramnik J.; Huttenhower, Curtis] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02142 USA. [Sokol, Harry; Devaney, Kathryn L.; Korzenik, Joshua; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Sokol, Harry; Devaney, Kathryn L.; Korzenik, Joshua; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Sokol, Harry; Devaney, Kathryn L.; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Shah, Samir A.; LeLeiko, Neal] Brown Univ, Warren Alpert Sch Med, Hasbro Childrens Hosp, Div Pediat Gastroenterol, Providence, RI 02903 USA. [Snapper, Scott B.; Bousvaros, Athos; Korzenik, Joshua] Harvard Univ, Childrens Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. [Snapper, Scott B.; Bousvaros, Athos; Korzenik, Joshua] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Sands, Bruce E.] Mt Sinai Sch Med, Dept Gastroenterol, New York, NY 10029 USA. RP Huttenhower, C (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM chuttenh@hsph.harvard.edu RI Shah, Shiraz/M-5132-2016; OI Shah, Shiraz/0000-0002-4665-577X; Morgan, Xochitl/0000-0002-6264-6961; sokol, harry/0000-0002-2914-1822; leleiko, neal/0000-0001-7699-1400; Huttenhower, Curtis/0000-0002-1110-0096 FU French Society of Gastroenterology; Bettencourt Schueller Foundation; Philippe Foundation; Arthur Sachs Scholarship; NIH [NIHU54HG004969, 1R21HD058828-01A1, 1R01HG005969]; Crohn's and Colitis Foundation of America; MacInnes and Rasmussen families; NSF [DBI-1053486]; ARO [W911NF-11-1-0473, W911NF-11-1-0429] FX We thank Wendy Garrett, Patrick Veiga, Ken Croitoru, and Mark Silverberg for their valuable comments on this manuscript and study, as well as Bruce Birren and the Broad Genome Sequencing and Analysis Program. This work was funded in part by grants from the French Society of Gastroenterology, the Bettencourt Schueller Foundation, the Philippe Foundation, and the Arthur Sachs Scholarship (HS); NIH (NIHU54HG004969) and the Crohn's and Colitis Foundation of America (DG and DVW); the philanthropic support of the MacInnes and Rasmussen families; NIH 1R21HD058828-01A1 to NL; and NIH 1R01HG005969, NSF DBI-1053486, and ARO W911NF-11-1-0473 and W911NF-11-1-0429 to CH. NR 100 TC 381 Z9 387 U1 27 U2 133 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 9 AR R79 DI 10.1186/gb-2012-13-9-r79 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 065XF UT WOS:000313182600008 PM 23013615 ER PT J AU Whiteman, NK Gloss, AD Sackton, TB Groen, SC Humphrey, PT Lapoint, RT Sonderby, IE Halkier, BA Kocks, C Ausubel, FM Pierce, NE AF Whiteman, Noah K. Gloss, Andrew D. Sackton, Timothy B. Groen, Simon C. Humphrey, Parris T. Lapoint, Richard T. Sonderby, Ida E. Halkier, Barbara A. Kocks, Christine Ausubel, Frederick M. Pierce, Naomi E. TI Genes Involved in the Evolution of Herbivory by a Leaf-Mining, Drosophilid Fly SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE Arabidopsis; Drosophila; glucosinolates; herbivory; host specialization; transcriptome ID MOLECULAR EVOLUTION; PHYLOGENETIC ANALYSIS; EXPRESSION ANALYSIS; INDUCED RESISTANCE; DNA-SEQUENCES; ARABIDOPSIS; MELANOGASTER; GENOME; STRESS; CYTOCHROME-P450 AB Herbivorous insects are among the most successful radiations of life. However, we know little about the processes underpinning the evolution of herbivory. We examined the evolution of herbivory in the fly, Scaptomyza flava, whose larvae are leaf miners on species of Brassicaceae, including the widely studied reference plant, Arabidopsis thaliana (Arabidopsis). Scaptomyza flava is phylogenetically nested within the paraphyletic genus Drosophila, and the whole genome sequences available for 12 species of Drosophila facilitated phylogenetic analysis and assembly of a transcriptome for S. flava. A time-calibrated phylogeny indicated that leaf mining in Scaptomyza evolved between 6 and 16 million years ago. Feeding assays showed that biosynthesis of glucosinolates, the major class of antiherbivore chemical defense compounds in mustard leaves, was upregulated by S. flava larval feeding. The presence of glucosinolates in wild-type (WT) Arabidopsis plants reduced S. flava larval weight gain and increased egg-adult development time relative to flies reared in glucosinolate knockout (GKO) plants. An analysis of gene expression differences in 5-day-old larvae reared on WT versus GKO plants showed a total of 341 transcripts that were differentially regulated by glucosinolate uptake in larval S. flava. Of these, approximately a third corresponded to homologs of Drosophila melanogaster genes associated with starvation, dietary toxin-, heat-, oxidation-, and aging-related stress. The upregulated transcripts exhibited elevated rates of protein evolution compared with unregulated transcripts. The remaining differentially regulated transcripts also contained a higher proportion of novel genes than the unregulated transcripts. Thus, the transition to herbivory in Scaptomyza appears to be coupled with the evolution of novel genes and the co-option of conserved stress-related genes. C1 [Whiteman, Noah K.; Gloss, Andrew D.; Humphrey, Parris T.; Lapoint, Richard T.] Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA. [Whiteman, Noah K.; Sackton, Timothy B.; Groen, Simon C.; Pierce, Naomi E.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Whiteman, Noah K.; Sackton, Timothy B.; Groen, Simon C.; Pierce, Naomi E.] Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA. [Sonderby, Ida E.; Halkier, Barbara A.] Univ Copenhagen, Dept Plant Biol & Biotechnol, Fac Life Sci, DK-1168 Copenhagen, Denmark. [Kocks, Christine] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Kocks, Christine; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Kocks, Christine] Harvard Univ, Dept Pediat, Sch Med, Cambridge, MA 02138 USA. [Ausubel, Frederick M.] Harvard Univ, Dept Genet, Sch Med, Cambridge, MA 02138 USA. RP Whiteman, NK (reprint author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA. EM whiteman@email.arizona.edu RI Groen, Simon/G-2443-2012; Halkier, Barbara/H-3196-2014; OI Halkier, Barbara/0000-0002-3742-702X; Sackton, Timothy/0000-0003-1673-9216 FU National Institutes of Health (NIH) (F32AI069732 to N. K. W. and 1F32GM086950 to T. B. S.), [F32AI0697321, F32GM086950]; University of Arizona; NIH [PO1 AI44220, R37 GM48707, P30 DK040561]; National Science Foundation (NSF) [MCB-0519898]; Harvard University Science and Engineering Committee Seed Fund for Interdisciplinary Science; Center for Insect Science at the University of Arizon [5K12GM000708-12] FX The authors are grateful to the following for advice, or technical help, or both: Dr Amir Karger who facilitated the preliminary 454 transcriptome analyses; Dr Frans Tax and Dr Lisa Nagy who facilitated the GUS histochemical assays. Dr Doug Futuyma, Dr Jill Anderson, and anonymous reviewers provided helpful feedback on an earlier version of the manuscript. Fly specimens were collected at the Rocky Mountain Biological Laboratory and under permits from the U. S. Forest Service Rocky Mountain Region to N. K. W. N. K. W. and T. B. S. were each supported by Kirschstein National Research Service Awards (NRSA) from the National Institutes of Health (NIH) (F32AI069732 to N. K. W. and 1F32GM086950 to T. B. S.), N. K. W. by a University of Arizona Faculty Seed Grant and a set- up award from the University of Arizona, C. K. by NIH grant PO1 AI44220, F. M. A. by grants from the National Science Foundation (NSF) (grant MCB-0519898) and NIH (R37 GM48707; P30 DK040561), and N. E. P. by a grant from the NSF (grant SES- 0750480). N. K. W., S. C. G., F. M. A., and N. E. P. were supported by a grant from the Harvard University's Provost Fund for Interfaculty Collaboration and a grant from the Harvard University Science and Engineering Committee Seed Fund for Interdisciplinary Science. A. D. G. and P. T. H. were each supported by NSF IGERT Program in Comparative Genomics doctoral fellowships through the University of Arizona. R. T. L. was supported by an NIH Postdoctoral Excellence in Research and Teaching (PERT) fellowship through the Center for Insect Science at the University of Arizona (5K12GM000708- 12). NR 93 TC 16 Z9 16 U1 0 U2 44 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2012 VL 4 IS 9 BP 900 EP 916 DI 10.1093/gbe/evs063 PG 17 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 066IA UT WOS:000313212900002 PM 22813779 ER PT J AU Goranson, A Boehnlein, J Drummond, D AF Goranson, Anders Boehnlein, James Drummond, David TI Commentary: A Homicide-Suicide Assessment Model SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Editorial Material ID VETERANS AB In this issue of the Journal, Dr. Paolo Roma and colleagues review international research spanning 60 years and highlight the centrality of psychiatric factors in the phenomenon of homicide-suicide (H-S). This commentary examines several challenges presented by definitional variability and the use of general sources as data. We suggest directions for future research, particularly using the established violence literature, to move toward intervention and management of H-S. We also examine the similarities between H-S and stalking and reflect on the potential for the stalking literature to inform the understanding and management of H-S. J Am Acad Psychiatry Law 40:472-5, 2012 C1 [Goranson, Anders] Portland VA Med Ctr, Northwest Network, MIRECC, Portland, OR USA. [Goranson, Anders; Boehnlein, James; Drummond, David] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Boehnlein, James] VA NW Network MIRECC, Portland, OR USA. [Drummond, David] Drummond Consulting & Training Serv, Portland, OR USA. RP Goranson, A (reprint author), 3710 SW US Vet Hosp Way, Portland, OR 97239 USA. EM anders.goranson@va.gov NR 19 TC 1 Z9 1 U1 0 U2 2 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2012 VL 40 IS 4 BP 472 EP 475 PG 4 WC Law; Psychiatry SC Government & Law; Psychiatry GA 060GN UT WOS:000312764600004 PM 23233467 ER PT J AU Piel, J AF Piel, Jennifer TI In the Aftermath of State v. Becker: A Review of State and Federal Jury Instructions on Insanity Acquittal Disposition SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article AB An important topic related to the insanity defense is what jurors should be told about the disposition of a defendant found not guilty by reason of insanity (NGRI). In the federal court system, jurors are not instructed about the consequences of an NGRI verdict. State courts, however, are divided on the question. The federal precedent, Shannon v. United States, and the most recent state case to rule on NGRI juror instructions, State v. Becker, are reviewed in detail. What follows is the author's critique of the principal arguments for and against a jury instruction on NGRI disposition. The author argues in favor of a jury instruction on the consequences of an NGRI verdict. J Am Acad Psychiatry Law 40:537-46, 2012 C1 [Piel, Jennifer] Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Piel, J (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM jennifer.piel@va.gov NR 24 TC 0 Z9 0 U1 0 U2 3 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2012 VL 40 IS 4 BP 537 EP 546 PG 10 WC Law; Psychiatry SC Government & Law; Psychiatry GA 060GN UT WOS:000312764600013 PM 23233476 ER PT S AU Zimmermann, BB Roche-Labarbe, N Surova, A Boas, DA Wolf, M Grant, PE Franceschini, MA AF Zimmermann, B. B. Roche-Labarbe, N. Surova, A. Boas, D. A. Wolf, M. Grant, P. E. Franceschini, M. A. BE Wolf, M Bucher, HU Rudin, M VanHuffel, S Wolf, U Bruley, DF Harrison, DK TI The Confounding Effect of Systemic Physiology on the Hemodynamic Response in Newborns SO OXYGEN TRANSPORT TO TISSUE XXXIII SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 38th Annual Conference of the International-Society-on-Oxygen-Transport-to-Tissue (ISOTT) CY JUL 18-23, 2010 CL Centro Stefano Franscini, ETH Zurich, Ascona, SWITZERLAND SP Int Soc Oxygen Transport Tissue (ISOTT), Swiss Natl Sci Fdn (FNSNF), Zurich Ctr Imaging Sci & Technol (CIMST), Swiss Acad Med Sci, Hamamatsu Photon, CASMED, Artinis Med Syst HO Centro Stefano Franscini, ETH Zurich ID NEAR-INFRARED SPECTROSCOPY; INFANT BRAIN; ACTIVATION; CORTEX; STIMULATION C1 [Zimmermann, B. B.; Roche-Labarbe, N.; Surova, A.; Boas, D. A.; Franceschini, M. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Zimmermann, B. B.; Wolf, M.] Univ Zurich Hosp, Clin Neonatol, Biomed Opt Res Lab, CH-8091 Zurich, Switzerland. [Grant, P. E.] Childrens Hosp, Boston, MA 02115 USA. RP Zimmermann, BB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM bzim@mgh.harvard.edu RI Roche-Labarbe, Nadege/N-9101-2015 OI Roche-Labarbe, Nadege/0000-0002-5010-0400 FU NIH [R01 HD42908] FX The authors thank all the families for their participation and the nurses, physicians, and staff in the Neonatal ICU, Special Care Nursery, Pediatric Neurology, and maternity units at the Massachusetts General Hospital. This work is supported by NIH grant R01 HD42908. NR 11 TC 4 Z9 4 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-1566-4 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2012 VL 737 BP 103 EP 109 DI 10.1007/978-1-4614-1566-4_16 PG 7 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BDG75 UT WOS:000313161700017 PM 22259089 ER PT J AU Goldstein, AD Hillman, RE AF Goldstein, Anatoly D. Hillman, Robert E. BE Zhang, C Joshi, J Bertino, E Thuraisingham, B TI Integration, Reuse and Sharing of Data on Voice Disorders SO 2012 IEEE 13TH INTERNATIONAL CONFERENCE ON INFORMATION REUSE AND INTEGRATION (IRI) LA English DT Proceedings Paper CT 13th IEEE International Conference on Information Reuse and Integration (IEEE IRI) / DIM / WICSOC / IEEE EM- RITE / IRI-HI CY AUG 08-10, 2012 CL Las Vegas, NV SP IEEE Syst Man & Cybernet Soc (IEEE SMC), Soc Informat Reuse & Integrat (SIRI), IEEE DE APM Website; Database for Voice Disorders; Healthcare Data Reuse; Online Data Sharing ID PATHOLOGY AB This paper describes a set of software tools which facilitate the automated processing of clinical voice (laryngeal) evaluation results, thus assisting doctors in voice disorder diagnostics, treatment and related research. The software tools include a website and a number of client/server applications developed by the authors at the Massachusetts General Hospital (MGH) for patient voice data entry, storage, retrieval, reporting, reuse and sharing on the web in de-identified form. The website software is integrated with existing commercial clinical software to support multi-institutional research collaboration. Design of the client/server applications includes automatic reuse of standard MGH outpatient and surgical schedules. An additional application has been developed to facilitate the remote retrieval and review of recorded clinical endoscopic examinations based on the reuse of commercial viewer software and database. A new general model is suggested for web-based sharing and mining of research data processed by means of a specific desktop computer program. C1 [Goldstein, Anatoly D.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Goldstein, AD (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM anatoly.goldstein@mgh.harvard.edu NR 14 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-2284-3 PY 2012 BP 407 EP 414 PG 8 WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BDC08 UT WOS:000312540300060 ER PT J AU Deng, Y Zhao, J Sakurai, D Kaufman, KM Edberg, JC Kimberly, RP Kamen, DL Gilkeson, GS Jacob, CO Scofield, RH Langefeld, CD Kelly, JA Alarcon-Riquelme, ME Harley, JB Vyse, TJ Freedman, BI Gaffney, PM Sivils, KM James, JA Niewold, TB Cantor, RM Chen, W Hahn, BH Brown, EE Tsao, BP AF Deng, Y. Zhao, J. Sakurai, D. Kaufman, K. M. Edberg, J. C. Kimberly, R. P. Kamen, D. L. Gilkeson, G. S. Jacob, C. O. Scofield, R. H. Langefeld, C. D. Kelly, J. A. Alarcon-Riquelme, M. E. Harley, J. B. Vyse, T. J. Freedman, B. I. Gaffney, P. M. Sivils, K. M. James, J. A. Niewold, T. B. Cantor, R. M. Chen, W. Hahn, B. H. Brown, E. E. Tsao, B. P. CA BIOLUPUS & GENLES Networks PROFILE TI MicroRNA-3148 modulates differential gene expression of the SLE-associated TLR7 variant SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract CT Meeting of the Lupus - New Targets, New Approaches CY SEP 27-30, 2012 CL Whistler, CANADA C1 [Deng, Y.; Zhao, J.; Sakurai, D.; Cantor, R. M.; Chen, W.; Hahn, B. H.; Tsao, B. P.] Univ Calif Los Angeles, Los Angeles, CA USA. [Kaufman, K. M.; Harley, J. B.; Vyse, T. J.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Cincinnati, OH USA. [Kaufman, K. M.; Harley, J. B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Edberg, J. C.; Kimberly, R. P.; Brown, E. E.] Univ Alabama Birmingham, Birmingham, AL USA. [Kamen, D. L.; Gilkeson, G. S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Jacob, C. O.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Scofield, R. H.; Kelly, J. A.; Alarcon-Riquelme, M. E.; Gaffney, P. M.; Sivils, K. M.; James, J. A.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Scofield, R. H.; James, J. A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Scofield, R. H.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Langefeld, C. D.] Wake Forest Univ Hlth Sci, Wake Forest, NC USA. [Alarcon-Riquelme, M. E.] Pfizer Univ Granada Junta Andalucia, Ctr Genom & Invest Oncol GENYO, Granada, Spain. [Vyse, T. J.] Kings Coll London, London, England. [Freedman, B. I.] Wake Forest Sch Med, Winston Salem, NC USA. [Niewold, T. B.] Univ Chicago, Gwen Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2012 VL 14 SU 3 MA A5 PG 2 WC Rheumatology SC Rheumatology GA 059OP UT WOS:000312715200006 ER PT J AU Leonard, DA McGrouther, DA Kurtz, JM Cetrulo, CL AF Leonard, David A. McGrouther, Duncan A. Kurtz, Josef M. Cetrulo, Curtis L., Jr. TI Tolerance Induction Strategies in Vascularized Composite Allotransplantation: Mixed Chimerism and Novel Developments SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Review ID MESENCHYMAL STEM-CELLS; BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; IMMATURE DENDRITIC CELLS; VERSUS-HOST-DISEASE; LARGE-ANIMAL-MODEL; TISSUE ALLOTRANSPLANTATION; COSTIMULATORY BLOCKADE; ALLOGRAFT TOLERANCE; SKIN ALLOGRAFTS AB Since the start of the clinical vascularized composite allotransplantation (VCA) era over a decade ago this field has witnessed significant developments in both basic and translational research. Transplant tolerance, defined as rejection-free acceptance of transplanted organs or tissues without long-term immunosuppression, holds the potential to revolutionize the field of VCA by removing the need for life-long immunosuppression. While tolerance of organ and vascularized composite transplants may be induced in small animal models by a variety of protocols, only mixed-chimerism-based protocols have successfully bridged the gap to preclinical study and to clinical trial in solid organ transplantation to date. In this paper we review the mixed-chimerism approach to tolerance induction, with specific reference to the field of VCA transplantation, and provide an overview of some novel cellular therapies as potential adjuvants to mixed chimerism in the development of tolerance induction protocols for clinical vascularized composite allotransplantation. C1 [Leonard, David A.; Kurtz, Josef M.; Cetrulo, Curtis L., Jr.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Leonard, David A.; McGrouther, Duncan A.] Univ Manchester, Dept Plast & Reconstruct Surg Res, Manchester, Lancs, England. [Kurtz, Josef M.] Univ Cambridge Emmanuel Coll, Dept Biol, Boston, MA USA. RP Cetrulo, CL (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. EM curt.cetrulo@tbrc.mgh.harvard.edu NR 79 TC 6 Z9 6 U1 0 U2 7 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1740-2522 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PY 2012 AR 863264 DI 10.1155/2012/863264 PG 8 WC Immunology SC Immunology GA 065SF UT WOS:000313168500001 ER PT J AU Pappalardo, F Brusic, V Frohlich, H AF Pappalardo, Francesco Brusic, Vladimir Froehlich, Holger TI Immune System Modeling and Related Pathologies SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Editorial Material C1 [Pappalardo, Francesco] Univ Catania, Dipartimento Sci Farmaco, I-95125 Catania, Italy. [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Froehlich, Holger] Univ Bonn, Bonn Aachen Int Ctr IT B IT, D-53113 Bonn, Germany. RP Pappalardo, F (reprint author), Univ Catania, Dipartimento Sci Farmaco, Viale Andrea Doria 6, I-95125 Catania, Italy. EM francesco.pappalardo@unict.it RI Pappalardo, Francesco/C-5832-2011; OI Pappalardo, Francesco/0000-0003-1668-3320; Frohlich, Holger/0000-0002-5328-1243 NR 7 TC 1 Z9 1 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1748-670X J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2012 AR 274702 DI 10.1155/2012/274702 PG 2 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 061IA UT WOS:000312840500001 ER PT J AU Gow, BJ Cheng, JL Baikie, ID Martinsen, OG Zhao, M Smith, S Ahn, AC AF Gow, Brian J. Cheng, Justine L. Baikie, Iain D. Martinsen, Orjan G. Zhao, Min Smith, Stephanie Ahn, Andrew C. TI Electrical Potential of Acupuncture Points: Use of a Noncontact Scanning Kelvin Probe SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID LAPLACE PLANE ANALYSIS; LOCI; SKIN; MICROSCOPY; MONOLAYERS; IMPEDANCE; TRANSPORT; CORROSION; LAYERS AB Objective. Acupuncture points are reportedly distinguishable by their electrical properties. However, confounders arising from skin-to-electrode contact used in traditional electrodermal methods have contributed to controversies over this claim. The Scanning Kelvin Probe is a state-of-the-art device that measures electrical potential without actually touching the skin and is thus capable of overcoming these confounding effects. In this study, we evaluated the electrical potential profiles of acupoints LI-4 and PC-6 and their adjacent controls. We hypothesize that acupuncture point sites are associated with increased variability in potential compared to adjacent control sites. Methods. Twelve healthy individuals were recruited for this study. Acupuncture points LI-4 and PC-6 and their adjacent controls were assessed. A 2 mm probe tip was placed over the predetermined skin site and adjusted to a tip-to-sample distance of 1.0 mm under tip oscillation settings of 62.4 Hz frequency. A 6 x 6 surface potential scan spanning a 1.0 cm x 1.0 cm area was obtained. Results. At both the PC-6 and LI-4 sites, no significant differences in mean potential were observed compared to their respective controls (Wilcoxon rank-sum test, P = 0.73 and 0.79, resp.). However, the LI-4 site was associated with significant increase in variability compared to its control as denoted by standard deviation and range (P = 0.002 and 0.0005, resp.). At the PC-6 site, no statistical differences in variability were observed. Conclusion. Acupuncture points may be associated with increased variability in electrical potential. C1 [Smith, Stephanie; Ahn, Andrew C.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Gow, Brian J.] Brigham & Womens Hosp, Osher Ctr Integrat Med, Boston, MA 02215 USA. [Cheng, Justine L.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Cheng, Justine L.] Harvard Univ, E Asian Programs, Cambridge, MA 02138 USA. [Baikie, Iain D.] KP Technol Ltd, Wick KW1 5LE, Scotland. [Martinsen, Orjan G.] Univ Oslo, Dept Phys, N-0316 Oslo, Norway. [Martinsen, Orjan G.] Oslo Univ Hosp, Rikshosp, Univ Hosp, Dept Biomed & Clin Engn, N-0027 Oslo, Norway. [Zhao, Min] Univ Calif Davis, Sch Med, Res Inst Regenerat Cures, Dept Dermatol, Sacramento, CA 95817 USA. [Zhao, Min] Univ Calif Davis, Sch Med, Res Inst Regenerat Cures, Dept Ophthalmol, Sacramento, CA 95817 USA. [Zhao, Min] Univ Aberdeen, Sch Med Sci, Aberdeen AB25 2ZD, Scotland. [Ahn, Andrew C.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Dept Med, Boston, MA 02215 USA. RP Ahn, AC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM aahn1@partners.org RI Martinsen, Orjan/M-4459-2014 OI Martinsen, Orjan/0000-0003-1632-4352 FU National Center for Complementary Alternative Medicine (NCCAM) [R21- AT005249, P30AT005895]; National Center for Research Resources [UL1RR025758] FX This research was supported by Grant nos. R21- AT005249 and P30AT005895 of the National Center for Complementary Alternative Medicine (NCCAM). The project described was supported by Clinical Translational Science Award UL1RR025758 to Harvard University and Massachusetts General Hospital from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Complementary Alternative Medicine or the National Center for Research Resources or the National Institutes of Health. The funders had no role in study design, the data collection and analysis, the decision to publish, or preparation of the paper. Professor I. D. Baikie is the CEO and founder of KP Technology, the manufacturer of the SKP5050 used in this study. The other coauthors have no conflict of interests to report. NR 41 TC 2 Z9 2 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2012 AR 632838 DI 10.1155/2012/632838 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 061PQ UT WOS:000312860800001 ER PT J AU Ku, MC Jaffe, JD Koche, RP Rheinbay, E Endoh, M Koseki, H Carr, SA Bernstein, BE AF Ku, Manching Jaffe, Jacob D. Koche, Richard P. Rheinbay, Esther Endoh, Mitsuhiro Koseki, Haruhiko Carr, Steven A. Bernstein, Bradley E. TI H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions SO GENOME BIOLOGY LA English DT Article DE Acetylation; bivalent; ChIP-Seq; H2A.Z; mass spectrometry; ubiquitination ID HISTONE H2A.Z; CHROMATIN STATE; TARGET GENES; ES CELLS; NUCLEOSOME; VARIANTS; MAPS; UBIQUITINATION; PROMOTERS; ENHANCERS AB Background: The histone variant H2A.Z has been implicated in nucleosome exchange, transcriptional activation and Polycomb repression. However, the relationships among these seemingly disparate functions remain obscure. Results: We mapped H2A.Z genome-wide in mammalian ES cells and neural progenitors. H2A.Z is deposited promiscuously at promoters and enhancers, and correlates strongly with H3K4 methylation. Accordingly, H2A.Z is present at poised promoters with bivalent chromatin and at active promoters with H3K4 methylation, but is absent from stably repressed promoters that are specifically enriched for H3K27 trimethylation. We also characterized post-translational modification states of H2A.Z, including a novel species dually-modified by ubiquitination and acetylation that is enriched at bivalent chromatin. Conclusions: Our findings associate H2A.Z with functionally distinct genomic elements, and suggest that post-translational modifications may reconcile its contrasting locations and roles. C1 [Ku, Manching; Koche, Richard P.; Rheinbay, Esther; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Dept Pathol, Boston, MA 02114 USA. [Ku, Manching; Koche, Richard P.; Rheinbay, Esther; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Ku, Manching; Koche, Richard P.; Rheinbay, Esther; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Ku, Manching; Jaffe, Jacob D.; Koche, Richard P.; Rheinbay, Esther; Carr, Steven A.; Bernstein, Bradley E.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Ku, Manching; Koche, Richard P.; Rheinbay, Esther; Bernstein, Bradley E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Koche, Richard P.] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Rheinbay, Esther] Boston Univ, Bioinformat Program, Boston, MA 02215 USA. [Rheinbay, Esther] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Endoh, Mitsuhiro; Koseki, Haruhiko] RIKEN Res Ctr Allergy & Immunol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. RP Ku, MC (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Dept Pathol, Simches Res Bldg,CPZN 8234, Boston, MA 02114 USA. EM Manching@Broadinstitute.org; Bernstein.Bradley@mgh.harvard.edu RI Koseki, Haruhiko/I-3825-2014 OI Koseki, Haruhiko/0000-0001-8424-5854 FU Croucher postdoctoral fellowship FX We thank Shawn Gillespie, Kaylyn Williamson, Tim Durham, Robbyn Issner, Xiaolan Zhang, Jing Gao, Chuck Epstein, Noam Shoresh, Michael Coyne and the Broad Institute Genome Sequencing Platform for providing reagents and assistance in generating, processing, displaying and submitting ChIP-Seq data. We are grateful for Dr Kevin Haigis and Krystle Kendall for the permission to use their Odyssey (R) Infrared Imaging system. We thank Dr Joseph A Goldman for helpful discussions on micrococcal nuclease digestion protocols. MK is supported in part by a Croucher postdoctoral fellowship. NR 49 TC 47 Z9 47 U1 3 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 10 SI SI AR R85 DI 10.1186/gb-2012-13-10-R85 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 065XQ UT WOS:000313183900004 PM 23034477 ER PT S AU Alcantara, D Josephson, L AF Alcantara, David Josephson, Lee BE DeLaFuente, JM Grazu, V TI Magnetic Nanoparticles for Application in Biomedical Sensing SO NANOBIOTECHNOLOGY: INORGANIC NANOPARTICLES VS ORGANIC NANOPARTICLES SE Frontiers of Nanoscience LA English DT Article; Book Chapter ID IRON-OXIDE NANOPARTICLES; ANTIFERROMAGNETIC NANOPARTICLES; MAGNETORESISTIVE SENSORS; MOLECULAR-INTERACTIONS; RELAXATION SWITCHES; CONTINUOUS-FLOW; NANOSENSORS; BIOSENSORS; CANCER; ASSAYS C1 [Alcantara, David; Josephson, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Nucl Med & Mol Imaging, Boston, MA 02115 USA. RP Alcantara, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Nucl Med & Mol Imaging, Boston, MA 02115 USA. NR 68 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1876-2778 BN 978-0-12-398304-6 J9 FRONT NANOSCI PY 2012 VL 4 BP 269 EP 289 DI 10.1016/B978-0-12-415769-9.00011-X PG 21 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Engineering; Science & Technology - Other Topics; Materials Science GA BCT63 UT WOS:000311364400012 ER PT S AU Wu, T Nieminen, TA Mohanty, S Miotke, J Meyer, RL Rubinsztein-Dunlop, H Berns, MW AF Wu, Tao Nieminen, Timo A. Mohanty, Samarendra Miotke, Jill Meyer, Ronald L. Rubinsztein-Dunlop, Halina Berns, Michael W. BE Dholakia, K Spalding, GC TI Directing growth cones of optic axons growing with laser scissors and laser tweezers SO OPTICAL TRAPPING AND OPTICAL MICROMANIPULATION IX SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Trapping and Optical Micromanipulation IX CY AUG 12-16, 2012 CL San Diego, CA SP SPIE DE laser tweezers; laser scissors; growth cone; axon; axonal growth AB We have combined a laser scissors and a laser tweezers to study, (1) the response of nerve fiber growth cones to laser-induced damage on single axons, and (2) localized microfluidic flow generated by laser-driven spinning birefringent particles. In the laser scissors study, sub-axotomy damage elicits a growth cone response whether damage is on the same or an adjacent axon. In laser tweezers study, the axon growth cones turn in response to the optically driven microfluidic flow. In summary, both the laser scissors and the laser tweezers studies elicit growth cone turning responses. C1 [Wu, Tao] Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. [Nieminen, Timo A.; Rubinsztein-Dunlop, Halina] Univ Queensland, Sch Math & Phys, BQuantum Sci Lab, Brisbane, Qld, Australia. [Wu, Tao; Miotke, Jill; Meyer, Ronald L.] Univ Calif Irvine, Department Dev & Cell Biol, Irvine, CA 92617 USA. [Berns, Michael W.] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92617 USA. [Berns, Michael W.] Harvard Med Sch & Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wu, T (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM taowu2012@gmail.com RI Rubinsztein-Dunlop, Halina/C-6762-2009; Nieminen, Timo/D-8904-2013; Rubinsztein-Dunlop, Halina/D-2387-2014 OI Rubinsztein-Dunlop, Halina/0000-0002-8332-2309; FU US Air Force [AFOSR FA9550-10-0538]; Beckman Laser Institute Foundation; Australian Research Council; School of Biological Science Grant FX The authors acknowledge supports from the US Air Force under grant AFOSR FA9550-10-0538, a grant from the Beckman Laser Institute Foundation (M.B.), a grant from the Australian Research Council (H.R.) and a School of Biological Science Grant (R.M.). NR 7 TC 0 Z9 0 U1 1 U2 4 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9175-6 J9 PROC SPIE PY 2012 VL 8458 AR 84580P DI 10.1117/12.930411 PG 6 WC Optics SC Optics GA BDF64 UT WOS:000313034500015 ER PT J AU Anaclet, C Lu, J Saper, C Fuller, PM AF Anaclet, C. Lu, J. Saper, C. Fuller, P. M. TI ACUTE PHARMACOGENETIC ACTIVATION OF THE MEDULLARY PARAFACIAL ZONE INDUCES SLOW-WAVE-SLEEP SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Anaclet, C.; Lu, J.; Saper, C.; Fuller, P. M.] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0018 BP A10 EP A10 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500020 ER PT J AU Babadi, B McKinney, S Tarokh, V Ellenbogen, JM AF Babadi, B. McKinney, S. Tarokh, V Ellenbogen, J. M. TI A DATA-DRIVEN BAYESIAN ALGORITHM FOR SLEEP SPINDLE DETECTION SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Babadi, B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Babadi, B.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [McKinney, S.] Stanford Univ, Inst Computat & Math Engn, Stanford, CA 94305 USA. [Tarokh, V] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Ellenbogen, J. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ellenbogen, J. M.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0386 BP A134 EP A134 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500388 ER PT J AU Barilla, HE Waldron, EA Plaksin, JR Segal, AG Findley, J Gehrman, P Jackson, NJ Grandner, MA Perlis, ML AF Barilla, H. E. Waldron, E. A. Plaksin, J. R. Segal, A. G. Findley, J. Gehrman, P. Jackson, N. J. Grandner, M. A. Perlis, M. L. TI RECRUITMENT STRATEGIES: WHAT METHODS YIELD THE MOST POTENTIAL PARTICIPANTS? SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Barilla, H. E.; Waldron, E. A.; Segal, A. G.; Findley, J.; Gehrman, P.; Perlis, M. L.] Univ Penn, Behav Sleep Med Program, Philadelphia, PA 19104 USA. [Waldron, E. A.] Philadelphia Coll Osteopath Med, Dept Psychol, Philadelphia, PA USA. [Plaksin, J. R.] NYU, Sch Med, New York, NY USA. [Segal, A. G.] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. [Gehrman, P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Jackson, N. J.; Grandner, M. A.] Univ Penn, Dept Med, Div Sleep Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0702 BP A236 EP A237 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996501220 ER PT J AU Barilla, HE Perlis, ML Grandner, MA Gehrman, P AF Barilla, H. E. Perlis, M. L. Grandner, M. A. Gehrman, P. TI RELATIONSHIPS BETWEEN AGE AND INSOMNIA SYMPTOMS SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Barilla, H. E.; Perlis, M. L.; Gehrman, P.] Univ Penn, Behav Sleep Med Program, Philadelphia, PA 19104 USA. [Grandner, M. A.] Univ Penn, Dept Med, Div Sleep Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Gehrman, P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0058 BP A23 EP A24 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500060 ER PT J AU Bianchi, MT Lipoma, T Darling, C AF Bianchi, M. T. Lipoma, T. Darling, C. TI DEVELOPMENT OF A SMART TEXTILE SHIRT FOR DETECTING BODY POSITION AND SLEEP DISORDERED BREATHING SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Bianchi, M. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bianchi, M. T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Lipoma, T.; Darling, C.] Nyx Devices, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1286 BP A434 EP A434 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502524 ER PT J AU Blanco-Centurion, C Liu, M Konadhode, R Pelluru, D van den Pol, A Shiromani, PJ AF Blanco-Centurion, C. Liu, M. Konadhode, R. Pelluru, D. van den Pol, A. Shiromani, P. J. TI OREXIN GENE TRANSFER INTO THE ZONA INCERTA NEURONS BLOCKS CATAPLEXY AND IMPROVES WAKE MAINTENANCE IN NARCOLEPTIC OREXIN-ATAXIN-3 TRANSGENIC MICE SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Blanco-Centurion, C.; Liu, M.; Konadhode, R.; Pelluru, D.; Shiromani, P. J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Shiromani, P. J.] Ralph H Johnson VAMC, Charleston, SC USA. [van den Pol, A.] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0017 BP A9 EP A9 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500019 ER PT J AU Bramoweth, AD Mosti, C Williams, JM Berry, RB McCrae, C AF Bramoweth, A. D. Mosti, C. Williams, J. M. Berry, R. B. McCrae, C. TI HEALTHCARE UTILIZATION PRE- AND POST-CBT FOR INSOMNIA SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Bramoweth, A. D.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. [Bramoweth, A. D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Mosti, C.] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [Williams, J. M.; McCrae, C.] Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL USA. [Berry, R. B.] Univ Florida, Dept Med, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1321 BP A446 EP A446 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502558 ER PT J AU Brown, RE McKenna, JT Yang, C Yanagawa, Y McCarley, RW AF Brown, R. E. McKenna, J. T. Yang, C. Yanagawa, Y. McCarley, R. W. TI SUBSTRATES OF CORTICAL ACTIVATION: INTERACTIONS BETWEEN CHOLINERGIC AND GABAERGIC NEURONS IN THE MOUSE BASAL FOREBRAIN SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Brown, R. E.; McKenna, J. T.; Yang, C.; McCarley, R. W.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Psychiat Div Sleep Med, Brockton, MA 02401 USA. [Yanagawa, Y.] Gunma Univ, Grad Sch Med, Maebashi, Gumma 371, Japan. [Yanagawa, Y.] Japan Sci & Technol Agcy, CREST, Chiyoda Ku, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0076 BP A30 EP A30 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500078 ER PT J AU Dworak, M Kim, T Kalinchuk, A McCarley, RW Basheer, R AF Dworak, M. Kim, T. Kalinchuk, A. McCarley, R. W. Basheer, R. TI REDUCED HOMOEOSTATIC SLEEP PRESSURE AND ACCOMPANIED CHANGES IN BRAIN ENERGETIC AFTER ORAL CREATINE-SUPPLEMENTATION IN RATS SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 VA Boston Healthcare Syst, W Roxbury, MA USA. Harvard Univ, Sch Med, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0008 BP A6 EP A6 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500010 ER PT J AU Eiseman, N Westover, MB Ellenbogen, JM Bianchi, MT AF Eiseman, N. Westover, M. B. Ellenbogen, J. M. Bianchi, M. T. TI THE RISK OF DIAGNOSTIC MISCLASSIFICATION IN SINGLE-NIGHT POLYSOMNOGRAPHY FOR SLEEP APNEA SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Eiseman, N.; Westover, M. B.; Ellenbogen, J. M.; Bianchi, M. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ellenbogen, J. M.; Bianchi, M. T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0462 BP A158 EP A159 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500464 ER PT J AU Fung, CH Martin, JL Jouldjian, S Josephson, KR Alessi, CA AF Fung, C. H. Martin, J. L. Jouldjian, S. Josephson, K. R. Alessi, C. A. TI DIFFICULTY WITH USE OF POSITIVE AIRWAY PRESSURE EQUIPMENT AND ADHERENCE TO THERAPY AMONG OLDER VETERANS: A PILOT STUDY SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Fung, C. H.; Martin, J. L.; Jouldjian, S.; Josephson, K. R.; Alessi, C. A.] VA Greater Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. [Fung, C. H.; Martin, J. L.; Alessi, C. A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0495 BP A169 EP A169 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996501014 ER PT J AU Fung, SJ Zhang, J Xi, M Sampogna, S Chase, MH AF Fung, S. J. Zhang, J. Xi, M. Sampogna, S. Chase, M. H. TI RECURRENT APNEA INDUCES APOPTOSIS IN HYPOGLOSSAL MOTONEURONS IN IN VIVO RATS SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Fung, S. J.; Zhang, J.; Xi, M.; Chase, M. H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Fung, S. J.; Zhang, J.; Xi, M.; Sampogna, S.; Chase, M. H.] Websci Int, Los Angeles, CA USA. [Chase, M. H.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0118 BP A44 EP A44 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500120 ER PT J AU Gehrman, P Girsh, L McCloskey, S Kuna, ST AF Gehrman, P. Girsh, L. McCloskey, S. Kuna, S. T. TI TELEHEALTH DELIVERY OF CBT-I IN VETERANS SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Gehrman, P.; Girsh, L.; McCloskey, S.; Kuna, S. T.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Gehrman, P.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kuna, S. T.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 6 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0718 BP A242 EP A242 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996501236 ER PT J AU Gehrman, P Barilla, H Hall, MH Buysse, DJ Perlis, ML Gooneratne, N Ross, RJ AF Gehrman, P. Barilla, H. Hall, M. H. Buysse, D. J. Perlis, M. L. Gooneratne, N. Ross, R. J. TI STRESS REACTIVITY IN INSOMNIA SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Gehrman, P.; Barilla, H.; Perlis, M. L.; Ross, R. J.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gehrman, P.; Ross, R. J.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Hall, M. H.; Buysse, D. J.] Univ Pittsburgh, Sleep Med Inst, Pittsburgh, PA USA. [Hall, M. H.; Buysse, D. J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Gooneratne, N.] Univ Penn, Perelman Sch Med, Div Geriatr Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0679 BP A229 EP A229 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996501197 ER PT J AU Gordhandas, A Buxton, OM Wang, W Carballeira, A Solet, JM Ellenbogen, JM AF Gordhandas, A. Buxton, O. M. Wang, W. Carballeira, A. Solet, J. M. Ellenbogen, J. M. TI HEART RATE ELEVATIONS FROM HOSPITAL SOUNDS DURING SLEEP SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Gordhandas, A.; Ellenbogen, J. M.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. [Buxton, O. M.; Wang, W.; Solet, J. M.; Ellenbogen, J. M.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Buxton, O. M.; Wang, W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Carballeira, A.] Cavanaugh Tocci Associates, Sudbury, MA USA. [Carballeira, A.] Berklee Sch Mus, Boston, MA USA. [Solet, J. M.] Massachusetts Gen Hosp, Dept Med, Cambridge Healh Alliance, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0945 BP A318 EP A318 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502183 ER PT J AU Harb, GC Cook, JM Thompson, R Ross, RJ AF Harb, G. C. Cook, J. M. Thompson, R. Ross, R. J. TI RESCRIPTING NIGHTMARES OF VETERANS WITH PTSD: RELATION TO TREATMENT OUTCOME SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Harb, G. C.; Ross, R. J.] Philadelphia VA Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. [Cook, J. M.] Yale Univ, Sch Med, New Haven, CT USA. [Cook, J. M.] Natl Ctr PTSD, West Haven, CT USA. [Thompson, R.] Univ Illinois, Chicago, IL USA. [Ross, R. J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1003 BP A338 EP A338 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502241 ER PT J AU Ho, VU Gottlieb, DJ AF Ho, V. U. Gottlieb, D. J. TI CALIBRATION MODEL FOR APNEA-HYPOPNEAS INDICES FOR AASM CRITERIA FOR HYPOPNEAS SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Ho, V. U.; Gottlieb, D. J.] Boston Univ, Boston, MA 02215 USA. [Gottlieb, D. J.] VA Boston Healthcare Syst, Pulm Crit Care & Sleep Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0439 BP A151 EP A152 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500441 ER PT J AU Holbrook, HM Sorrentino, E Maski, K Hanson, E Manoach, D Stickgold, R AF Holbrook, H. M. Sorrentino, E. Maski, K. Hanson, E. Manoach, D. Stickgold, R. TI THE RELATIONSHIP BETWEEN TOTAL SLEEP TIME AND BEHAVIORAL AND EMOTIONAL INDICATORS IN CHILDREN WITH AUTISM SPECTRUM DISORDERS (ASD) SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Holbrook, H. M.; Sorrentino, E.; Hanson, E.] Childrens Hosp Boston, Boston, MA USA. [Hanson, E.; Stickgold, R.] Harvard Univ, Sch Med, Boston, MA USA. [Maski, K.] Childrens Hosp Boston, Boston, MA USA. [Stickgold, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Manoach, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Manoach, D.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1096 BP A369 EP A369 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502334 ER PT J AU Hughes, JM Jouldjian, S Washington, D Alessi, CA Martin, JL AF Hughes, J. M. Jouldjian, S. Washington, D. Alessi, C. A. Martin, J. L. TI DOES COMORBID PTSD PREDICT SUBJECTIVE AND OBJECTIVE SLEEP DISTURBANCE AMONG WOMEN VETERANS? SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Hughes, J. M.; Jouldjian, S.; Alessi, C. A.; Martin, J. L.] VA Greater Los Angeles, Geriatr Res Educ & Clin Ctr, North Hills, CA USA. [Washington, D.; Alessi, C. A.; Martin, J. L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Washington, D.] VA Greater Los Angeles, Ctr Excellence Healthcare Provider Behav, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1216 BP A409 EP A409 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502454 ER PT J AU Joffe, H Hall, JE Economou, N Kim, S Regan, S Crawford, S White, D AF Joffe, H. Hall, J. E. Economou, N. Kim, S. Regan, S. Crawford, S. White, D. TI OBJECTIVE INTERRUPTION OF SLEEP CONTINUITY BY HOT FLASHES: A GONADOTROPIN-RELEASING HORMONE AGONIST MODEL SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Joffe, H.; Economou, N.; Kim, S.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Ctr Womens Mental Hlth, Boston, MA 02115 USA. [Hall, J. E.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Reprod Endocrinol, Boston, MA USA. [Regan, S.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Gen Med, Boston, MA USA. [Crawford, S.] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA USA. [White, D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Sleep Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1218 BP A409 EP A410 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502456 ER PT J AU Kalinchuk, A Kim, S McCarley, RW Basheer, R AF Kalinchuk, A. Kim, S. McCarley, R. W. Basheer, R. TI THE ROLE OF CHOLINERGIC BASAL FOREBRAIN NEURONS IN THE BIOCHEMICAL AND ELECTROPHYSIOLOGICAL CHANGES IN THE CORTEX DURING SLEEP DEPRIVATION SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Kalinchuk, A.; McCarley, R. W.; Basheer, R.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Kim, S.] Brown Univ, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0003 BP A4 EP A5 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500005 ER PT J AU Khalilzadeh, O Bang, J Wakeman, DG Tamaki, M Hamalainen, M Watanabe, T Sasaki, Y AF Khalilzadeh, O. Bang, J. Wakeman, D. G. Tamaki, M. Haemaelaeinen, M. Watanabe, T. Sasaki, Y. TI SLOW-WAVE MEG ACTIVITY IN PRIMARY VISUAL CORTICAL AREA DURING SLEEP AFTER VISUAL PERCEPTUAL LEARNING: THE ROLE OF SLEEP IN VISUAL PERCEPTUAL LEARNING SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Khalilzadeh, O.; Wakeman, D. G.; Haemaelaeinen, M.; Sasaki, Y.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Khalilzadeh, O.; Bang, J.; Watanabe, T.] Boston Univ, Vis Sci Lab, Boston, MA 02215 USA. [Tamaki, M.] Adv Telecommun Res Inst Int, Kyoto, Japan. RI Hamalainen, Matti/C-8507-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0262 BP A92 EP A93 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500264 ER PT J AU Khawaja, O Sarwar, A Gaziano, JM Djousse, L AF Khawaja, O. Sarwar, A. Gaziano, J. M. Djousse, L. TI SLEEP DURATION AND RISK OF ATRIAL FIBRILLATION IN THE PHYSICIANS' HEALTH STUDY SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Khawaja, O.; Gaziano, J. M.; Djousse, L.] VA Boston Healthcare Syst, MAVERIC, Boston, MA USA. [Gaziano, J. M.; Djousse, L.] VA Boston Healthcare Syst, GRECC, Boston, MA USA. [Khawaja, O.; Gaziano, J. M.; Djousse, L.] Brigham & Womens Hospita, Div Aging, Boston, MA 02115 USA. [Khawaja, O.; Gaziano, J. M.; Djousse, L.] Harvard Univ, Meidcal Sch, Boston, MA USA. [Sarwar, A.] Lahey Clin Fdn, Burlington, MA USA. [Sarwar, A.] Tufts Univ Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0943 BP A317 EP A317 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502181 ER PT J AU Kim, T McKenna, JT McNally, JM Chen, L Kocsis, B Deisseroth, K Strecker, RE McCarley, RW Brown, RE Basheer, R AF Kim, T. McKenna, J. T. McNally, J. M. Chen, L. Kocsis, B. Deisseroth, K. Strecker, R. E. McCarley, R. W. Brown, R. E. Basheer, R. TI PARVALBUMIN-POSITIVE BASAL FOREBRAIN NEURONS ENTRAIN CORTICAL GAMMA OSCILLATIONS AND PROMOTE WAKEFULNESS SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Kim, T.; McKenna, J. T.; McNally, J. M.; Chen, L.; Strecker, R. E.; McCarley, R. W.; Brown, R. E.; Basheer, R.] VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. [Kim, T.; McKenna, J. T.; McNally, J. M.; Chen, L.; Strecker, R. E.; McCarley, R. W.; Brown, R. E.; Basheer, R.] Harvard Univ, Sch Med, Boston, MA USA. [Kocsis, B.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Deisseroth, K.] Stanford Unvivers, Stanford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0078 BP A31 EP A31 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500080 ER PT J AU Lapierre, JL Kosenko, P Kodama, T Peever, J Mukhametov, L Lyamin, O Siegel, J AF Lapierre, J. L. Kosenko, P. Kodama, T. Peever, J. Mukhametov, L. Lyamin, O. Siegel, J. TI UNLIKE ACETYLCHOLINE, CORTICAL SEROTONIN RELEASE IS NOT LATERALIZED DURING ASYMMETRICAL SLOW WAVE SLEEP IN THE FUR SEAL SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Lapierre, J. L.; Lyamin, O.; Siegel, J.] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. [Lapierre, J. L.; Lyamin, O.; Siegel, J.] Vet Adm Greater Los Angeles Healthcare Syst, Neurobiol Res, North Hills, CA USA. [Lapierre, J. L.; Peever, J.] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON, Canada. [Kosenko, P.; Mukhametov, L.; Lyamin, O.] Utrish Dolphinarium Ltd, Res Unit, Moscow, Russia. [Kosenko, P.] 2nd S Fed Univ, Rostov Na Donu, Russia. [Kodama, T.] Tokyo Metropolitan Inst Med Sci, Dept Dementia & Higher Brain Funct, Tokyo 113, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0064 BP A26 EP A26 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500066 ER PT J AU Manoach, D Wamsley, EJ Shinn, AK Tucker, MA Ono, KE McKinley, SK Ely, AV Goff, DC Stickgold, R AF Manoach, D. Wamsley, E. J. Shinn, A. K. Tucker, M. A. Ono, K. E. McKinley, S. K. Ely, A., V Goff, D. C. Stickgold, R. TI THE EFFECTS OF ESZOPICLONE ON SLEEP SPINDLES AND MEMORY CONSOLIDATION IN SCHIZOPHRENIA SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Manoach, D.] MGH, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wamsley, E. J.; Tucker, M. A.; McKinley, S. K.; Ely, A., V; Stickgold, R.] BIDMC, Boston, MA USA. [Shinn, A. K.] McLean Hosp, Psychot Disorders Div, Belmont, MA 02178 USA. [Manoach, D.; Wamsley, E. J.; Shinn, A. K.; Tucker, M. A.; Ono, K. E.; McKinley, S. K.; Ely, A., V; Goff, D. C.; Stickgold, R.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1006 BP A339 EP A339 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502244 ER PT J AU Marino, M Li, Y Rueschman, M Winkelman, J Ellenbogen, JM Solet, JM Dulin, H Berkman, L Buxton, OM AF Marino, M. Li, Y. Rueschman, M. Winkelman, J. Ellenbogen, J. M. Solet, J. M. Dulin, H. Berkman, L. Buxton, O. M. TI ACCURACY, SENSITIVITY, AND SPECIFICITY OF A WRIST ACTIGRAPHY ALGORITHM FOR SLEEP/WAKE AND WASO AS COMPARED TO POLYSOMNOGRAPHY SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Marino, M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Y.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Rueschman, M.; Dulin, H.; Buxton, O. M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Winkelman, J.; Ellenbogen, J. M.; Solet, J. M.; Buxton, O. M.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Winkelman, J.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Ellenbogen, J. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Solet, J. M.] Cambridge Healh Alliance, Massachusetts Gen Hosp, Dept Med, Cambridge, MA USA. [Berkman, L.] Harvard Univ, Sch Publ Hlth, Harvard Populat Ctr, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1306 BP A440 EP A441 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502544 ER PT J AU Martin, JL Hughes, JM Jouldjian, S Washington, D Alessi, CA AF Martin, J. L. Hughes, J. M. Jouldjian, S. Washington, D. Alessi, C. A. TI PREDICTORS OF HEALTH-RELATED QUALITY OF LIFE AMONG WOMEN VETERANS WITH INSOMNIA SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Martin, J. L.; Hughes, J. M.; Jouldjian, S.; Alessi, C. A.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Martin, J. L.; Washington, D.; Alessi, C. A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Washington, D.] VA Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1258 BP A423 EP A424 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502496 ER PT J AU Maski, K Holbrook, H Hanson, E Manoach, D Stickgold, R AF Maski, K. Holbrook, H. Hanson, E. Manoach, D. Stickgold, R. TI SLEEP DEPENDENT MEMORY CONSOLIDATION IN CHILDREN WITH AUTISM SPECTRUM DISORDERS (ASD) USING A PROBABILISTIC CATEGORICAL LEARNING TASK SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Maski, K.] Childrens Hosp Boston, Boston, MA USA. [Maski, K.; Hanson, E.; Manoach, D.; Stickgold, R.] Harvard Univ, Sch Med, Boston, MA USA. [Stickgold, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Holbrook, H.; Hanson, E.] Childrens Hosp Boston, Boston, MA USA. [Manoach, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Manoach, D.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1094 BP A369 EP A369 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502332 ER PT J AU Matura, L McDonough, A Carroll, D AF Matura, L. McDonough, A. Carroll, D. TI IS DIFFICULTY SLEEPING ASSOCIATED WITH HEALTH OUTCOMES IN PULMONARY ARTERIAL HYPERTENSION? SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Matura, L.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [McDonough, A.] Univ Massachusetts, Dept Nursing, Lowell, MA USA. [Matura, L.; McDonough, A.; Carroll, D.] Massachusetts Gen Hosp, Munn Ctr Nursing Res, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0935 BP A314 EP A314 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502173 ER PT J AU McKenna, JT Shifflett, LB Winston, S Bolortuya, Y Ferrarini, MA Goodhue, GD Kocsis, B McCarley, RW Strecker, RE AF McKenna, J. T. Shifflett, L. B. Winston, S. Bolortuya, Y. Ferrarini, M. A. Goodhue, G. D. Kocsis, B. McCarley, R. W. Strecker, R. E. TI DORSAL RAPHE NUCLEUS MEDIATION OF APNEA-INDUCED CORTICAL AROUSALS SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [McKenna, J. T.; Shifflett, L. B.; Winston, S.; Bolortuya, Y.; McCarley, R. W.; Strecker, R. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02401 USA. [Ferrarini, M. A.; Goodhue, G. D.] Stonehill Coll, Easton, MA USA. [Kocsis, B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0119 BP A45 EP A45 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500121 ER PT J AU Montesi, S Malhotra, A Bakker, J AF Montesi, S. Malhotra, A. Bakker, J. TI A META-ANALYSIS OF THE EFFECTS OF POSITIVE AIRWAY PRESSURE TREATMENT ON HYPERTENSION SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Montesi, S.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Montesi, S.; Malhotra, A.; Bakker, J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Sleep Disorders Res Program, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0867 BP A292 EP A292 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502105 ER PT J AU Mosti, CB Williams, JM Bramoweth, AD Berry, RB McCrae, C AF Mosti, C. B. Williams, J. M. Bramoweth, A. D. Berry, R. B. McCrae, C. TI HEALTHCARE UTILIZATION OF INSOMNIA PATIENTS WITH COMORBID DEPRESSION AND/OR ANXIETY SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Mosti, C. B.; Williams, J. M.; Berry, R. B.; McCrae, C.] Univ Florida, Gainesville, FL USA. [Bramoweth, A. D.] Univ Pittsburgh, Pittsburgh, PA USA. [Berry, R. B.] Malcom Randall VA Med Ctr, Gainesville, FL USA. [Bramoweth, A. D.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0739 BP A248 EP A248 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996501255 ER PT J AU Sassower, KC AF Sassower, K. C. TI DIMINISHED PHASIC EYE AND BODY MOVEMENTS IN SYMPTOMATIC AND NEUROLOGICALLY COMPROMISED NEWBORN INFANTS SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Sassower, K. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1093 BP A368 EP A368 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502331 ER PT J AU Sharkey, KM Kim, S Regan, S Crawford, S Joffe, H AF Sharkey, K. M. Kim, S. Regan, S. Crawford, S. Joffe, H. TI MENSTRUAL CYCLE PHASE, REPRODUCTIVE HORMONE LEVELS, AND SLEEP IN PREMENOPAUSAL WOMEN SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Sharkey, K. M.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence, RI 02903 USA. [Kim, S.; Joffe, H.] Harvard Univ, Sch Med, Dept Psychiat, Ctr Womens Mental Hlth,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Regan, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Med Div,Dept Med, Boston, MA USA. [Crawford, S.] Univ Massachusetts, Sch Med, Dept Preventat & Behav Med, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 1248 BP A420 EP A420 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502486 ER PT J AU Sherry, D Collins, EG AF Sherry, D. Collins, E. G. TI INFLUENCE OF SLEEP ON DYSPNEA, EMOTIONAL FUNCTION, AND PHYSICAL FUNCTION IN HEART FAILURE PATIENTS WITH CARDIAC RESYNCHRONIZATION THERAPY SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Sherry, D.; Collins, E. G.] US Dept Vet Affairs, Hines, IL USA. [Sherry, D.; Collins, E. G.] Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0948 BP A319 EP A319 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502186 ER PT J AU Shinn, AK Masters, G Pfaff, D Cohen, BM Manoach, D Ongur, D Stickgold, R AF Shinn, A. K. Masters, G. Pfaff, D. Cohen, B. M. Manoach, D. Ongur, D. Stickgold, R. TI DIAGNOSTIC SPECIFICITY OF SLEEP-DEPENDENT MEMORY IMPAIRMENTS IN PSYCHIATRIC INPATIENTS SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Shinn, A. K.; Masters, G.; Pfaff, D.; Cohen, B. M.; Ongur, D.] McLean Hosp, Belmont, MA 02178 USA. [Manoach, D.] Massachusetts Gen Hosp Charlestown Navy Yard, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Stickgold, R.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Shinn, A. K.; Cohen, B. M.; Manoach, D.; Ongur, D.; Stickgold, R.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0985 BP A332 EP A332 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502223 ER PT J AU Soehner, AM Gruber, J Gershon, A Talbot, LS Eidelman, P Hairston, IS Harvey, AG AF Soehner, A. M. Gruber, J. Gershon, A. Talbot, L. S. Eidelman, P. Hairston, I. S. Harvey, A. G. TI DOES SLEEPING TOO LITTLE MAKE YOU FEEL TOO MUCH? AN INVESTIGATION OF SLEEP DURATION AND EMOTION REACTIVITY IN INTER-EPISODE BIPOLAR DISORDER AND HEALTHY ADULTS SO SLEEP LA English DT Meeting Abstract CT 26th Annual Meeting of the Association-of-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Assoc Profess Sleep Soc (APSS) C1 [Soehner, A. M.; Harvey, A. G.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Gruber, J.] Yale Univ, New Haven, CT USA. [Talbot, L. S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Talbot, L. S.] San Francisco VA Med Ctr, San Francisco, CA USA. [Eidelman, P.] San Francisco Bay Ctr Cognit Therapy, Oakland, CA USA. [Hairston, I. S.] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0976 BP A329 EP A329 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996502214 ER PT J AU Thankachan, S Fuller, PM Lu, J AF Thankachan, S. Fuller, P. M. Lu, J. TI LOCOMOTION- AND STATE-DEPENDENT ACTIVITY OF LATERAL PONTINE TEGMENTUM NEURONS: A PUTATIVE NEUROANATOMIC SUBSTRATE FOR THE MESENCEPHALIC LOCOMOTOR REGION (MLR) SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Thankachan, S.; Fuller, P. M.; Lu, J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Thankachan, S.; Fuller, P. M.; Lu, J.] Harvard Univ, Sch Med, Boston, MA USA. [Thankachan, S.] Harvard Univ, Sch Med, Brockton, MA 02401 USA. [Thankachan, S.] VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0092 BP A35 EP A36 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500094 ER PT J AU Waldron, EA Byrne, M Barilla, H Gehrman, P Findley, J Grandner, MA Jackson, NJ Perlis, ML AF Waldron, E. A. Byrne, M. Barilla, H. Gehrman, P. Findley, J. Grandner, M. A. Jackson, N. J. Perlis, M. L. TI DIFFERENCES IN INSOMNIA SYMPTOM SEVERITY AMONG PRIMARY INSOMNIA, INSOMNIA COMORBID WITH DEPRESSION OR INSOMNIA COMORBID WITH CHRONIC PAIN SO SLEEP LA English DT Meeting Abstract CT 26th Annual Meeting of the Association-of-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Assoc Profess Sleep Soc (APSS) C1 [Waldron, E. A.; Byrne, M.; Barilla, H.; Gehrman, P.; Findley, J.; Perlis, M. L.] Univ Penn, Behav Sleep Med Program, Philadelphia, PA 19104 USA. [Waldron, E. A.] Philadelphia Coll Osteopath Med, Dept Psychol, Philadelphia, PA USA. [Byrne, M.] Univ Sci, Dept Behav & Social Sci, Philadelphia, PA USA. [Gehrman, P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Grandner, M. A.; Jackson, N. J.] Univ Penn, Dept Med, Div Sleep Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0713 BP A240 EP A240 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996501231 ER PT J AU Waldron, EA Barilla, HE Segal, AG Plaksin, JR Findley, J Gehrman, P Grandner, MA Jackson, NJ Perlis, ML AF Waldron, E. A. Barilla, H. E. Segal, A. G. Plaksin, J. R. Findley, J. Gehrman, P. Grandner, M. A. Jackson, N. J. Perlis, M. L. TI EVALUATION OF COUNTY OF RESIDENCE ON INSOMNIA SEVERITY SO SLEEP LA English DT Meeting Abstract CT 26th Annual Meeting of the Association-of-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Assoc Profess Sleep Soc (APSS) C1 [Waldron, E. A.; Barilla, H. E.; Segal, A. G.; Findley, J.; Gehrman, P.; Perlis, M. L.] Univ Penn, Behav Sleep Med Program, Philadelphia, PA 19104 USA. [Waldron, E. A.] Philadelphia Coll Osteopath Med, Dept Psychol, Philadelphia, PA USA. [Segal, A. G.] Drexel Univ, Dept Psychol, Philadelphia, PA 19104 USA. [Plaksin, J. R.] NYU, Sch Med, New York, NY USA. [Gehrman, P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Jackson, N. J.; Perlis, M. L.] Univ Penn, Dept Med, Div Sleep Med, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0712 BP A240 EP A240 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996501230 ER PT J AU Williams, RH Iqbal, SZ Saper, C Arrigoni, E AF Williams, R. H. Iqbal, S. Z. Saper, C. Arrigoni, E. TI THE EFFECTS OF CARBACHOL, NOREPHINEPHRINE, AND SEROTONIN ON THE GLUTAMATERGIC NEURONS OF THE SUBLATERODORSAL NUCLEUS SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 BIDMC, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0093 BP A36 EP A36 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500095 ER PT J AU Zhang, J Fung, SJ Xi, M Sampogna, S Chase, MH AF Zhang, J. Fung, S. J. Xi, M. Sampogna, S. Chase, M. H. TI HYPOCRETINERGIC RECEPTOR TYPE 1, NOT TYPE 2, IS EXPRESSED BY CANCER CELLS OF THE HUMAN COLON SO SLEEP LA English DT Meeting Abstract CT Annual Meeting of the Associated-Professional-Sleep-Societies (APSS) CY JUN 09-13, 2012 CL Boston, MA SP Associated Professi Sleep Soc (APSS) C1 [Zhang, J.; Fung, S. J.; Xi, M.; Sampogna, S.; Chase, M. H.] WebSci Int, Los Angeles, CA USA. [Zhang, J.; Fung, S. J.; Xi, M.; Chase, M. H.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chase, M. H.] Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2012 VL 35 SU S MA 0032 BP A14 EP A14 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063KH UT WOS:000312996500034 ER PT S AU Frank, JA AF Frank, James A. BE Fromm, M Schulzke, JD TI Claudins and alveolar epithelial barrier function in the lung SO BARRIERS AND CHANNELS FORMED BY TIGHT JUNCTION PROTEINS I SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE alveolar epithelium; tight junction; claudin; acute lung injury; cancer ID TIGHT-JUNCTION PROTEINS; OVARIAN-CANCER; FLUID TRANSPORT; BREAST-CANCER; UP-REGULATION; II CELLS; EXPRESSION; PERMEABILITY; INJURY; IDENTIFICATION AB The alveolar epithelium of the lung constitutes a unique interface with the outside environment. This thin barrier must maintain a surface for gas transfer while being continuously exposed to potentially hazardous environmental stimuli. Small differences in alveolar epithelial barrier properties could therefore have a large impact on disease susceptibility or outcome. Moreover, recent work has focused attention on the alveolar epithelium as central to several lung diseases, including acute lung injury and idiopathic pulmonary fibrosis. Although relatively little is known about the function and regulation of claudin tight junction proteins in the lung, new evidence suggests that environmental stimuli can influence claudin expression and alveolar barrier function in human disease. This review considers recent advances in the understanding of the role of claudins in the breakdown of the alveolar epithelial barrier in disease and in epithelial repair. C1 [Frank, James A.] San Francisco VA Med Ctr, Dept Med, Div Pulm & Crit Care Med, No Calif Inst Res & Educ, San Francisco, CA 94121 USA. [Frank, James A.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA. [Frank, James A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP Frank, JA (reprint author), San Francisco VA Med Ctr, Dept Med, Div Pulm & Crit Care Med, No Calif Inst Res & Educ, 4150 Clement St,Box 111D, San Francisco, CA 94121 USA. EM James.frank@ucsf.edu FU NHLBI NIH HHS [R01 HL088440, R21 HL111707, R56 HL088440] NR 64 TC 15 Z9 15 U1 0 U2 12 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-873-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1257 BP 175 EP 183 DI 10.1111/j.1749-6632.2012.06533.x PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BDB53 UT WOS:000312485200021 PM 22671604 ER PT S AU Lengerke, C Daley, GQ AF Lengerke, Claudia Daley, George Q. BE Kanz, L Fibbe, WE Lengerke, C Dick, JE TI Caudal genes in blood development and leukemia SO HEMATOPOIETIC STEM CELLS VIII SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 8th International Conference and Workshop on Hematopoietic Stem Cells CY SEP 22-24, 2011 CL Univ Tubingen, Tubingen, GERMANY HO Univ Tubingen DE Cdx; hematopoiesis; leukemia; Hox; blood development ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; T(14/18) LYMPHOMA-CELLS; CDX-HOX PATHWAY; RETINOIC ACID; ZEBRAFISH HEMATOPOIESIS; ECTOPIC EXPRESSION; HOMEOBOX GENES; MOUSE EMBRYOS AB Members of the caudal gene family (in mice and humans: Cdx1, Cdx2, and Cdx4) have been studied during early development as regulators of axial elongation and anteroposterior patterning. In the adult, Cdx1 and Cdx2, but not Cdx4, have been intensively explored for their function in intestinal tissue homeostasis and the pathogenesis of gastrointestinal cancers. Involvement in embryonic hematopoiesis was first demonstrated in zebrafish, where cdx genes render posterior lateral plate mesoderm competent to respond to genes specifying hematopoietic fate, and compound mutations in cdx genes thus result in a bloodless phenotype. Parallel studies performed in zebrafish embryos and murine embryonic stem cells (ESCs) delineate conserved pathways between fish and mammals, corroborating a BMP/Wnt-Cdx-Hox axis during blood development that can be employed to augment derivation of blood progenitors from pluripotent stem cells in vitro. The molecular regulation of Cdx genes appears complex, as more recent data suggest involvement of non-Hox-related mechanisms and the existence of auto-and cross-regulatory loops governed by morphogens. Here, we will review the role of Cdx genes during hematopoietic development by comparing effects in zebrafish and mice and discuss their participation in malignant blood diseases. C1 [Daley, George Q.] Childrens Hosp, Boston, MA 02115 USA. [Daley, George Q.] Dana Farber Canc Inst, Stem Cell Transplantat Program, Boston, MA 02115 USA. [Lengerke, Claudia] Univ Tubingen, Med Ctr, D-72076 Tubingen, Germany. RP Daley, GQ (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM claudia.lengerke@med.uni-tuebingen.de; george.daley@childrens.harvard.edu OI Lengerke, Claudia/0000-0001-5442-2805 FU Deutsche Krebshilfe (Max-Eder program); Deutsche Forschungsgemeinschaft [SFB773]; University of Tubingen (Fortune program); Bohringer Ingelheim Foundation (Exploration Grant program); NIH [R24DK092760, UO1-HL100001, RC4-DK090913, P50HG005550]; Roche Foundation for Anemia Research, Alex's Lemonade Stand; Ellison Medical Foundation; Doris Duke Charitable Foundation; ARRA stimulus [package-RC2-HL102815]; Harvard Stem Cell Institute FX C.L. is supported by grants from the Deutsche Krebshilfe (Max-Eder program), the Deutsche Forschungsgemeinschaft (SFB773), the University of Tubingen (Fortune program), and the Bohringer Ingelheim Foundation (Exploration Grant program). G.Q.D. is an investigator of the Howard Hughes Medical Institute and supported by Grants from the NIH (R24DK092760, 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, the Ellison Medical Foundation, the Doris Duke Charitable Foundation, and the Harvard Stem Cell Institute. G.Q.D. is an affiliated member of the Broad Institute and a senior scientist of the Manton Center for Orphan Disease Research. NR 65 TC 3 Z9 5 U1 0 U2 6 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 BN 978-1-57331-867-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1266 BP 47 EP 54 DI 10.1111/j.1749-6632.2012.06625.x PG 8 WC Cell Biology; Hematology; Multidisciplinary Sciences SC Cell Biology; Hematology; Science & Technology - Other Topics GA BDC42 UT WOS:000312595400007 PM 22901255 ER PT J AU Eiseman, NA Westover, MB Ellenbogen, JM Bianchi, MT AF Eiseman, Nathaniel A. Westover, M. Brandon Ellenbogen, Jeffrey M. Bianchi, Matt T. TI The Impact of Body Posture and Sleep Stages on Sleep Apnea Severity in Adults SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Supine-dominant; REM-dominant; false-negative; phenotype ID RAPID EYE-MOVEMENT; TO-NIGHT VARIABILITY; HYPOPNEA INDEX; HEART HEALTH; NEGATIVE POLYSOMNOGRAM; SURGICAL MODIFICATIONS; POSITIONAL THERAPY; UPPER AIRWAY; METAANALYSIS; ASSOCIATION AB Study Objectives: Determining the presence and severity of obstructive sleep apnea (OSA) is based on apnea and hypopnea event rates per hour of sleep. Making this determination presents a diagnostic challenge, given that summary metrics do not consider certain factors that influence severity, such as body position and the composition of sleep stages. Methods: We retrospectively analyzed 300 consecutive diagnostic PSGs performed at our center to determine the impact of body position and sleep stage on sleep apnea severity. Results: The median percent of REM sleep was 16% (reduced compared to a normal value of similar to 25%). The median percent supine sleep was 65%. Fewer than half of PSGs contained > 10 min in each of the 4 possible combinations of REM/NREM and supine/non-supine. Half of patients had > 2-fold worsening of the apnea-hypopnea index (AHI) in REM sleep, and 60% had > 2-fold worsening of AHI while supine. Adjusting for body position had greater impact on the AHI than adjusting for reduced REM%. Misclassification-specifically underestimation of OSA severity-is attributed more commonly to body position (20% to 40%) than to sleep stage (similar to 10%). Conclusions: Supine-dominance and REM-dominance commonly contribute to AHI underestimation in single-night PSGs. Misclassification of OSA severity can be mitigated in a patient-specific manner by appropriate consideration of these variables. The results have implications for the interpretation of single-night measurements in clinical practice, especially with trends toward home testing devices that may not measure body position or sleep stage. C1 [Eiseman, Nathaniel A.; Westover, M. Brandon; Ellenbogen, Jeffrey M.; Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ellenbogen, Jeffrey M.; Bianchi, Matt T.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang 7 Neurol,55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Department of Neurology, Massachusetts General Hospital; Young Clinician Award from the Center for Integration of Medicine and Innovative Technology FX This was not an industry supported study. Dr Bianchi and Dr Ellenbogen receive funding from the Department of Neurology, Massachusetts General Hospital. Dr Bianchi receives funding from a Young Clinician Award from the Center for Integration of Medicine and Innovative Technology. Dr Bianchi has a patent pending on a home sleep monitoring device. The other authors have indicated no financial conflicts of interest. NR 60 TC 26 Z9 26 U1 0 U2 4 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2012 VL 8 IS 6 BP 655 EP + DI 10.5664/jcsm.2258 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 057ZW UT WOS:000312604500005 PM 23243399 ER PT J AU Garza, JLB Catalano, PJ Katz, JN Huysmans, MA Dennerlein, JT AF Garza, Jennifer L. Bruno Catalano, Paul J. Katz, Jeffrey N. Huysmans, Maaike A. Dennerlein, Jack T. TI Developing a Framework for Predicting Upper Extremity Muscle Activities, Postures, Velocities, and Accelerations During Computer Use: The Effect of Keyboard Use, Mouse Use, and Individual Factors on Physical Exposures SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE anthropometry; biomechanics; task-based exposure assessment ID RISK-FACTORS; USE TIME; BIOMECHANICS; DISORDERS; FORCES; TASK; LOAD AB Prediction models were developed based on keyboard and mouse use in combination with individual factors that could be used to predict median upper extremity muscle activities, postures, velocities, and accelerations experienced during computer use. In the laboratory, 25 participants performed five simulated computer trials with different amounts of keyboard and mouse use ranging from a highly keyboard-intensive trial to a highly mouse-intensive trial. During each trial, muscle activity and postures of the shoulder and wrist and velocities and accelerations of the wrists, along with percentage keyboard and mouse use, were measured. Four individual factors (hand length, shoulder width, age, and gender) were also measured on the day of data collection. Percentage keyboard and mouse use explained a large amount of the variability in wrist velocities and accelerations. Although hand length, shoulder width, and age were each significant predictors of at least one median muscle activity, posture, velocity, or acceleration exposure, these individual factors explained very little variability in addition to percentage keyboard and mouse use in any of the physical exposures investigated. The amounts of variability explained for models predicting median wrist velocities and accelerations ranged from 75 to 84% but were much lower for median muscle activities and postures (050%). RMS errors ranged between 8 to 13% of the range observed. While the predictions for wrist velocities and accelerations may be able to be used to improve exposure assessment for future epidemiologic studies, more research is needed to identify other factors that may improve the predictions for muscle activities and postures. C1 [Dennerlein, Jack T.] Northeastern Univ, Bouve Coll Hlth Sci, Dept Phys Therapy, Boston, MA 02115 USA. [Garza, Jennifer L. Bruno; Katz, Jeffrey N.; Dennerlein, Jack T.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Catalano, Paul J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Catalano, Paul J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Katz, Jeffrey N.; Dennerlein, Jack T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. [Huysmans, Maaike A.; Dennerlein, Jack T.] Vrije Univ Amsterdam Med Ctr, Dept Publ & Occupat Hlth, Amsterdam, Netherlands. [Huysmans, Maaike A.; Dennerlein, Jack T.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands. [Huysmans, Maaike A.] TNO VU Vumc, Res Ctr Phys Act Work & Hlth, Amsterdam, Netherlands. RP Dennerlein, JT (reprint author), Northeastern Univ, Bouve Coll Hlth Sci, Dept Phys Therapy, 6 Robinson Hall,360 Huntington Ave, Boston, MA 02115 USA. EM j.dennerlein@neu.edu OI Dennerlein, Jack/0000-0001-7703-643X FU CDC/NIOSH [1-R01-0H-03997, 1-R01-0H-08781]; NIH/NIAMS [P60 AR 47782] FX The authors would like to acknowledge Dr. Peter Johnson for his contribution to the experimental and equipment design for this study, as well as the funding sources for this project: CDC/NIOSH 1-R01-0H-03997 (PI: Dennerlein) and CDC/NIOSH 1-R01-0H-08781 (PI: Dennerlein). Dr. Katz is supported in part by NIH/NIAMS P60 AR 47782. NR 28 TC 3 Z9 3 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PY 2012 VL 9 IS 12 BP 691 EP 698 DI 10.1080/15459624.2012.728927 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 057XC UT WOS:000312596700005 ER PT S AU Simard, JM Geng, ZH Silver, FL Sheth, KN Kimberly, WT Stern, BJ Colucci, M Gerzanich, V AF Simard, J. Marc Geng, Zhihua Silver, Frank L. Sheth, Kevin N. Kimberly, W. Taylor Stern, Barney J. Colucci, Mario Gerzanich, Volodymyr BE DelZoppo, GJ Alexandrov, AV TI Does inhibiting Sur1 complement rt-PA in cerebral ischemia? SO THROMBOLYSIS AND ACUTE STROKE TREATMENT: PREPARING FOR THE NEXT DECADE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 11th Symposium on Thrombolysis and Acute Stroke Treatment (TAST) - Preparing for the Next Decade CY DEC 01-03, 2011 CL New York Acad Sci, Manhattan, NY SP Natl Inst Neurol Disorders & Stroke (NINDS) HO New York Acad Sci DE rt-PA; Sur1; glyburide; MMP-9; cerebral ischemia; stroke ID TISSUE-PLASMINOGEN-ACTIVATOR; BLOOD-BRAIN-BARRIER; MATRIX-METALLOPROTEINASE INHIBITION; EMBOLIC FOCAL ISCHEMIA; HEMORRHAGIC TRANSFORMATION; REPERFUSION INJURY; RAT-BRAIN; TIME WINDOW; MATRIX-METALLOPROTEINASE-9 EXPRESSION; INTRACEREBRAL HEMORRHAGE AB Hemorrhagic transformation (HT) associated with recombinant tissue plasminogen activator (rt-PA) complicates and limits its use in stroke. Here, we provide a focused review on the involvement of matrix metalloproteinase 9 (MMP-9) in rt-PA-associated HT in cerebral ischemia, and we review emerging evidence that the selective inhibitor of the sulfonylurea receptor 1 (Sur1), glibenclamide (U.S. adopted name, glyburide), may provide protection against rt-PA-associated HT in cerebral ischemia. Glyburide inhibits activation of MMP-9, ameliorates edema formation, swelling, and symptomatic hemorrhagic transformation, and improves preclinical outcomes in several clinically relevant models of stroke, both without and with rt-PA treatment. A retrospective clinical study comparing outcomes in diabetic patients with stroke treated with rt-PA showed that those who were previously on and were maintained on a sulfonylurea fared significantly better than those whose diabetes was managed without sulfonylureas. Inhibition of Sur1 with injectable glyburide holds promise for ameliorating rt-PA-associated HT in stroke. C1 [Simard, J. Marc; Geng, Zhihua; Gerzanich, Volodymyr] Univ Maryland, Sch Med, Dept Neurosurg, Baltimore, MD 21201 USA. [Simard, J. Marc] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Simard, J. Marc] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Silver, Frank L.] Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada. [Sheth, Kevin N.; Stern, Barney J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Kimberly, W. Taylor] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Colucci, Mario] Univ Aldo Moro, Dept Biomed Sci & Human Oncol, Bari, Italy. RP Simard, JM (reprint author), Univ Maryland, Sch Med, Dept Neurosurg, 22 S Greene St,Suite S12D, Baltimore, MD 21201 USA. EM msimard@smail.umaryland.edu OI Colucci, Mario/0000-0001-9146-8095 FU NHLBI NIH HHS [R01 HL082517] NR 116 TC 14 Z9 14 U1 0 U2 10 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2012 VL 1268 BP 95 EP 107 DI 10.1111/j.1749-6632.2012.06705.x PG 13 WC Multidisciplinary Sciences; Clinical Neurology; Peripheral Vascular Disease SC Science & Technology - Other Topics; Neurosciences & Neurology; Cardiovascular System & Cardiology GA BDC41 UT WOS:000312593800015 PM 22994227 ER PT J AU Davies, JK Barbon, CM Voskertchian, A Nadler, LM Guinan, EC AF Davies, Jeff K. Barbon, Christine M. Voskertchian, Annie Nadler, Lee M. Guinan, Eva C. TI Ex Vivo Alloanergization With Belatacept: A Strategy to Selectively Modulate Alloresponses After Transplantation SO CELL TRANSPLANTATION LA English DT Article DE Transplantation; Belatacept; Costimulatory blockade; Alloreactivity; Anergization; Regulatory T cells ID VERSUS-HOST-DISEASE; T-CELL-ACTIVATION; RANDOMIZED CLINICAL-TRIAL; RENAL-TRANSPLANTATION; COSTIMULATION BLOCKADE; REGULATORY CELLS; NTREG CELLS; PHASE-III; IN-VIVO; LYMPHOCYTES AB Ex vivo alloanergization of human immune cells, via allostimulation in the presence of costimulatory blockade with either a combination of anti-B7.1 and anti-B7.2 antibodies or first-generation cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), induces alloantigen-specific hyporesponsiveness and expands alloantigen-specific regulatory T cells (Treg). We have successfully used this approach in the clinical setting of haploidentical hematopoietic stem cell transplantation. Recently, the in vivo use of a new second-generation CTLA4-Ig, belatacept, has shown promise in controlling alloresponses after transplantation of both human kidneys and islet cells. We therefore compared the efficiency of first- and second-generation CTLA4-Ig in alloanergizing human peripheral blood mononuclear cells (PBMCs) and investigated whether ex vivo alloanergization with belatacept could he used to engineer an alloantigen-specific immunoregulatory population of autologous cells suitable for administration to recipients of cellular or solid organ transplant recipients. Alloanergization of HLA-mismatched human PBMCs with belatacept resulted in a greater reduction in subsequent alloresponses than alloanergization with first generation CTLA4-Ig. Moreover, subsequent ex vivo re-exposure of alloanergized cells to alloantigen in the absence of belatacept resulted in a significant expansion of Tregs with enhanced alloantigen-specific suppressive function. Alloanergized PBMCs retained functional Epstein-Barr virus (EBV)-specific T-cell responses, and expanded Tregs did not suppress EBV-specific proliferation of autologous cells. These results suggest that ex vivo alloanergization with belatacept provides a platform to engineer populations of recipient Treg with specificity for donor alloantigens but without nonspecific suppressive capacity. The potential advantages of such cells for solid organ transplantation include (1) reduction of the need for nonspecific immunosuppression, (2) retention of pathogen-specific immunity, and (3) control of graft rejection, if used as an intervention. C1 [Guinan, Eva C.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Davies, Jeff K.; Nadler, Lee M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Davies, Jeff K.] Queen Mary Univ London, Barts Canc Inst, Ctr Haematooncol, London, England. [Davies, Jeff K.; Barbon, Christine M.; Voskertchian, Annie; Nadler, Lee M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Guinan, Eva C.] Harvard Univ, Sch Med, Boston, MA USA. RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. EM eva_guinan@dfci.harvard.edu FU NIH [R21 CA137645, U19CA100265]; Frank J. Hanna Jr., Carlson Family; Pan Mass Challenge-Shea Family Funds; American Society for Blood and Marrow Transplantation; UK Medical Research Council FX The authors would like to thank Bristol Myers Squibb for providing belatacept and Lisa L. Brennan BSN for her assistance in undertaking this work. This work was supported by NIH R21 CA137645 and U19CA100265 with additional support from the Frank J. Hanna Jr., Carlson Family, and Pan Mass Challenge-Shea Family Funds. J.K.D. was a recipient via New Investigator award from the American Society for Blood and Marrow Transplantation and a Clinician Scientist award from the UK Medical Research Council. Authorship was determined in accordance with according to the ICMJE criteria (http://www.icmje.org/ethical_1author.html). J.K.D. and C.M.B. contributed equally to the work, conceiving, designing and performing experiments, analyzing data, and writing the manuscript. A. V. performed experiments. L.M.N. provided critical reagents and commented critically on the manuscript. E.C.G. conceived and designed experiments and wrote the manuscript. The authors declare no conflicts of interest. NR 52 TC 10 Z9 10 U1 2 U2 2 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2012 VL 21 IS 9 BP 2047 EP 2061 DI 10.3727/096368912X637479 PG 15 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 055QN UT WOS:000312431600018 PM 22507909 ER PT J AU Edmonds, ML Milan, SJ Brenner, BE Camargo, CA Rowe, BH AF Edmonds, Marcia L. Milan, Stephen J. Brenner, Barry E. Camargo, Carlos A., Jr. Rowe, Brian H. TI Inhaled steroids for acute asthma following emergency department discharge SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review DE AcuteDisease; Administration, Inhalation; Anti-Asthmatic Agents [administration & dosage]; Anti-Inflammatory Agents [administration & dosage]; Asthma [drug therapy]; Emergency Service, Hospital; Glucocorticoids [administration & dosage]; Patient Discharge; Randomized Controlled Trials as Topic; Steroids; Humans ID RANDOMIZED CONTROLLED-TRIAL; NEBULIZED FLUTICASONE PROPIONATE; MODERATE ACUTE ASTHMA; DOUBLE-BLIND TRIAL; ORAL PREDNISOLONE; BRONCHIAL-ASTHMA; BECLOMETHASONE DIPROPIONATE; SYSTEMIC CORTICOSTEROIDS; BUDESONIDE THERAPY; EARLY INTERVENTION AB Background Patients with acute asthma treated in the emergency department (ED) are frequently treated with inhaled beta(2)-agonists and systemic corticosteroids after discharge. The use of inhaled corticosteroids (ICS) following discharge may also be beneficial in improving patient outcomes after acute asthma. Objectives To determine the effectiveness of ICS on outcomes in the treatment of acute asthma following discharge from the ED. To quantify the effectiveness of ICS therapy on acute asthma following ED discharge, when used in addition to, or as a substitute for, systemic corticosteroids. Search methods Controlled clinical trials (CCTs) were identified from the Cochrane Airways Review Group register, which consists of systematic searches of EMBASE, MEDLINE and CINAHL databases supplemented by handsearching of respiratory journals and conference proceedings. In addition, primary authors and pharmaceutical companies were contacted to identify eligible studies. Bibliographies from included studies, known reviews and texts also were searched. The searches have been conducted up to September 2012 Selection criteria We included both randomised controlled trials (RCTs) and quasi-RCTs. Studies were included if patients were treated for acute asthma in the ED or its equivalent, and following ED discharge were treated with ICS therapy either in addition to, or as a substitute for, oral corticosteroids. Two review authors independently assessed articles for potential relevance, final inclusion and methodological quality. Data collection and analysis Data were extracted independently by two review authors, or confirmed by the study authors. Several authors and pharmaceutical companies provided unpublished data. The data were analysed using the Cochrane Review Manager software. Where appropriate, individual and pooled dichotomous outcomes were reported as odds ratios (OR) or relative risks (RR) with 95% confidence intervals (CIs). Where appropriate, individual and pooled continuous outcomes were reported as mean differences (MD) or standardized mean differences (SMD) with 95% CIs. The primary analysis employed a fixed effect model and heterogeneity is reported using I-squared (I 2) statistics. Main results Twelve trials were eligible for inclusion. Three of these trials, involving a total of 909 patients, compared ICS plus systemic corticosteroids versus oral corticosteroid therapy alone. There was no demonstrated benefit of ICS therapy when used in addition to oral corticosteroid therapy in the trials. Relapses were reduced; however, this was not statistically significant with the addition of ICS therapy (OR 0.68; 95% CI 0.46 to 1.02; 3 studies; N = 909). In addition, no statistically significant differences were demonstrated between the two groups for relapses requiring admission, quality of life, symptom scores or adverse effects. Nine trials, involving a total of 1296 patients compared high-dose ICS therapy alone versus oral corticosteroid therapy alone after ED discharge. There were no significant differences demonstrated between ICS therapy alone versus oral corticosteroid therapy alone for relapse rates (OR 1.00; 95% CI 0.66 to 1.52; 4 studies; N = 684), admissions to hospital, or in the secondary outcomes of beta(2)-agonist use, symptoms or adverse events. However, the sample size was not adequate to exclude the possibility of either treatment being significantly inferior and people with severe asthma were excluded from these trials. Authors' conclusions There is insufficient evidence that ICS therapy provides additional benefit when used in combination with standard systemic corticosteroid therapy upon ED discharge for acute asthma. There is some evidence that high-dose ICS therapy alone may be as effective as oral corticosteroid therapy when used in mild asthmatics upon ED discharge; however, the confidence intervals were too wide to be confident of equal effectiveness. Further research is needed to clarify whether ICS therapy should be employed in acute asthma treatment following ED discharge. The review does not suggest any reason to stop usual treatment with ICS following ED discharge, even if a course of oral corticosteroids are prescribed. C1 [Edmonds, Marcia L.] Schulich Sch Med & Dent, London, ON N6A 5W9, Canada. [Milan, Stephen J.] Univ London, London, England. [Brenner, Barry E.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Rowe, Brian H.] Univ Alberta, Dept Emergency Med, Edmonton, AB, Canada. [Rowe, Brian H.] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada. RP Edmonds, ML (reprint author), Schulich Sch Med & Dent, 800 Commissioners Rd,E1-102, London, ON N6A 5W9, Canada. EM medmonds@ualberta.ca FU Astra; Boehringer-Ingelheim; Forest; Glaxo Wellcome; Merck; Sepracor; Department of Emergency Medicine, University of Alberta, Edmonton, AB, Canada; NHS Research and Development, UK; National Institute of Health Research, UK; NIH, USA [HL-03533]; Canadian Institutes of Health Research (CIHR), Ottawa, ON, Canada FX The authors who have been involved in this review have done so without any known conflicts of interest. Drs. Rowe, Brenner and Camargo were involved as lead investigators in the primary studies of oral corticosteroid plus ICS versus oral corticosteroid alone. Drs. Camargo, Rowe and Brenner have received unrestricted educational grants for research from Astra, Boehringer-Ingelheim, Forest, Glaxo Wellcome, Merck and Sepracor. However, none of the authors is considered a paid consultant by any pharmaceutical company that produces ICS agents.; Department of Emergency Medicine, University of Alberta, Edmonton, AB, Canada.; NHS Research and Development, UK.; National Institute of Health Research (SJM), UK.; HL-03533 NIH (CA Camargo Jr), USA.; Canadian Institutes of Health Research (CIHR), Ottawa, ON (BH Rowe), Canada. NR 126 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2012 IS 12 AR CD002316 DI 10.1002/14651858.CD002316.pub2 PG 92 WC Medicine, General & Internal SC General & Internal Medicine GA 053FL UT WOS:000312256300013 ER PT S AU Dobrev, I Harrington, EJ Cheng, T Furlong, C Rosowski, JJ AF Dobrev, I. Harrington, E. J. Cheng, T. Furlong, C. Rosowski, J. J. BE Furlong, C Gorecki, C Novak, EL TI Digital holographic otoscope for measurements of the human tympanic membrane in-vivo SO INTERFEROMETRY XVI: APPLICATIONS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Interferometry XVI - Applications CY AUG 13-16, 2012 CL San Diego, CA SP SPIE DE digital holography; holographic otoscope; mechatronics; otology; positioning system ID UTILITY AB We are developing an advanced computer-controlled digital optoelectronic holographic system (DOEHS) for diagnosing middle-ear conductive disorders and investigating the causes of failure of middle-ear surgical procedures. Our current DOEHS system can provide near real-time quantitative measurements of the sound-induced nano-meter scale motion of the eardrum. The DOEHS have been deployed and is currently being tested in clinical conditions, where it is being optimized for in-vivo measurements of patients. The stability of the measurement system during examination is crucial as the non-ideal clinical environment presents disturbances larger than the measured quantities from several domains - thermal, optical, electrical and mechanical. Examples include disturbances are due to heartbeat breathing, patients head's motion as well as environment induced mechanical disturbances (0.1-60Hz, 0.01-100 mu m). In this paper we focus on our current progress in the analysis and implementation of various acquisition strategies and algorithms for minimization of the measurement error due to mechanical disturbances in a clinic. We have also developed and implemented a versatile and modular otoscope head (OH) design providing a variety of capabilities for acoustic and displacement measurements of both post-mortem samples of varying sizes (1-12mm) as well as in-vivo examination of patients. The OH offers hybrid on-axis and off axis digital Furrier holographic setup for high resolution (lambda/35) 4 phase step measurements as well as fast (<0.1ms) single frame measurements for improved performance in the clinical environment. We also focus on the development of a mechatronic positioning system (MOP) for aiding in the localization of the TM in patients. C1 [Dobrev, I.; Harrington, E. J.; Furlong, C.] Worcester Polytech Inst, Dept Mech Engn, NanoEngn Sci Technol NEST, Ctr Holog Studies & Laser MicromechTron CHSLT, Worcester, MA 01609 USA. [Cheng, T.; Furlong, C.; Rosowski, J. J.] Eaton Peabody Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Rosowski, J. J.] Harvard Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA USA. RP Dobrev, I (reprint author), Worcester Polytech Inst, Dept Mech Engn, NanoEngn Sci Technol NEST, Ctr Holog Studies & Laser MicromechTron CHSLT, Worcester, MA 01609 USA. FU National Institute on Deafness and Other Communication Disorders (NIDCD); Massachusetts Eye and Ear Infirmary (MEEI); Mittal Fund FX This work has been funded by the National Institute on Deafness and Other Communication Disorders (NIDCD), the Massachusetts Eye and Ear Infirmary (MEEI), and the Mittal Fund. The authors also gratefully acknowledge the support of the NanoEngineering, Science, and Technology (NEST) program at the Worcester Polytechnic Institute, Mechanical Engineering Department. NR 14 TC 2 Z9 2 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9211-1 J9 PROC SPIE PY 2012 VL 8494 AR 849409 DI 10.1117/12.954633 PG 9 WC Materials Science, Characterization & Testing; Optics SC Materials Science; Optics GA BCZ59 UT WOS:000312211100009 ER PT S AU Dizdaroglu, B Ataer-Cansizoglu, E Kalpathy-Cramer, J Keck, K Chiang, MF Erdogmus, D AF Dizdaroglu, Bekir Ataer-Cansizoglu, Esra Kalpathy-Cramer, Jayashree Keck, Katie Chiang, Michael F. Erdogmus, Deniz BE Santamaria, I ArenasGarcia, J CampsValls, G Erdogmus, D PerezCruz, F Larsen, J TI Level Sets for Retinal Vasculature Segmentation Using Seeds from Ridges and Edges from Phase Maps SO 2012 IEEE INTERNATIONAL WORKSHOP ON MACHINE LEARNING FOR SIGNAL PROCESSING (MLSP) SE IEEE International Workshop on Machine Learning for Signal Processing LA English DT Proceedings Paper CT 22nd IEEE International Workshop on Machine Learning for Signal Processing (MLSP) CY SEP 23-26, 2012 CL Santander, SPAIN SP IEEE, IEEE Signal Proc Soc DE Fundus image; retinal vasculature analysis; vessel segmentation; level sets; phase map for edge detection; principal curves as ridges ID BLOOD-VESSEL SEGMENTATION; IMAGE SEGMENTATION; PLUS DISEASE; GRAY-LEVEL; PREMATURITY; RETINOPATHY; DIAGNOSIS AB In this paper, we present a novel modification to level set based automatic retinal vasculature segmentation approaches. The method introduces ridge sample extraction for sampling the vasculature centerline and phase map based edge detection for accurate region boundary detection. Segmenting the vasculature in fundus images has been generally challenging for level set methods employing classical edge-detection methodologies. Furthermore, initialization with seed points determined by sampling vessel centerlines using ridge identification makes the method completely automated. The resulting algorithm is able to segment vasculature in fundus imagery accurately and automatically. Quantitative results supplemented with visual ones support this observation. The methodology could be applied to the broader class of vessel segmentation problems encountered in medical image analytics. C1 [Dizdaroglu, Bekir] Karadeniz Tech Univ, Dept Comp Engn, Trabzon, Turkey. NE Univ, Cognit Syst Lab, Boston, MA USA. [Dizdaroglu, Bekir; Ataer-Cansizoglu, Esra; Erdogmus, Deniz] Massachusetts Gen Hosp, Martinos Imaging Ctr, Boston, MA USA. [Kalpathy-Cramer, Jayashree] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR USA. [Keck, Katie; Chiang, Michael F.] Oregon Hlth & Sci Univ, Dept Med Informat, Portland, OR USA. RP Dizdaroglu, B (reprint author), Karadeniz Tech Univ, Dept Comp Engn, Trabzon, Turkey. FU TUBITAK; NSF; NIH FX This work is partially supported by grants from TUBITAK, NSF, and NIH. NR 15 TC 0 Z9 0 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2161-0363 BN 978-1-4673-1026-0 J9 IEEE INT WORKS MACH PY 2012 PG 6 WC Automation & Control Systems; Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Automation & Control Systems; Computer Science; Engineering GA BCY19 UT WOS:000311966000021 ER PT J AU Li, JF Dong, SW Townsend, SD Dean, T Gardella, TJ Danishefsky, SJ AF Li, Jianfeng Dong, Suwei Townsend, Steven D. Dean, Thomas Gardella, Thomas J. Danishefsky, Samuel J. TI Chemistry as an Expanding Resource in Protein Science: Fully Synthetic and Fully Active Human Parathyroid Hormone-Related Protein (1-141) SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE biological activity; dethiylation; ligation; proteins; solid-phase synthesis ID NATIVE CHEMICAL LIGATION; PHASE PEPTIDE-SYNTHESIS; BREAST-CANCER CELLS; PTH/PTHRP RECEPTOR; PTHRP; BONE; EXPRESSION; CYSTEINE; DESULFURIZATION; CONFORMATIONS C1 [Li, Jianfeng; Dong, Suwei; Townsend, Steven D.; Danishefsky, Samuel J.] Sloan Kettering Inst Canc Res, Bioorgan Chem Lab, New York, NY 10065 USA. [Dean, Thomas; Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Dean, Thomas; Gardella, Thomas J.] Harvard Univ, Sch Med, Boston, MA USA. [Danishefsky, Samuel J.] Columbia Univ, Dept Chem, New York, NY 10027 USA. RP Danishefsky, SJ (reprint author), Sloan Kettering Inst Canc Res, Bioorgan Chem Lab, 1275 York Ave, New York, NY 10065 USA. EM s-danishefsky@ski.mskcc.org RI Li, Jianfeng/F-5057-2014 OI Li, Jianfeng/0000-0002-8838-3872 FU NIH [HL25848]; Weill Cornell Medical School [CA062948] FX This research was supported by NIH grant HL25848 (S.J.D.). S. D. T. is grateful to Weill Cornell Medical School for an NIH postdoctoral fellowship (CA062948). NR 50 TC 13 Z9 13 U1 2 U2 29 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 49 BP 12263 EP 12267 DI 10.1002/anie.201207603 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 045OP UT WOS:000311706500021 PM 23124999 ER PT J AU Iezzoni, LI AF Iezzoni, Lisa I. TI Aging with an existing physical disability SO INTERNATIONAL JOURNAL OF INTEGRATED CARE LA English DT Meeting Abstract DE aging; disability; personal beliefs; functional limitations C1 [Iezzoni, Lisa I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. EM liezzoni@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU IGITUR, UTRECHT PUBLISHING & ARCHIVING SERVICES PI URTRECHT PA POSTBUS 80124, URTRECHT, 3508 TC, NETHERLANDS SN 1568-4156 J9 INT J INTEGR CARE JI Int. J. Integr. Care PY 2012 VL 12 SU 3 PG 1 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 049WP UT WOS:000312014400010 ER PT J AU Cardozo, DL Raymond, L White, B AF Cardozo, David Lopes Raymond, Laurie White, Benjamin TI A structured PBL tutorial involving small teams for teaching the human nervous system SO MEDICAL TEACHER LA English DT Article ID PROBLEM-SOLVING SKILLS; EDUCATIONAL PRACTICE AB Background: The Human Nervous System and Behavior course at Harvard Medical School (HMS) incorporates a hybrid model of problem-based learning. Student preparation for and participation in the tutorial seemed to be insufficient. Aims: We sought to increase student engagement in tutorial by creating a structured approach, which included assigned roles for students, weekly testing, formal cornerstone presentations, and a weekly self-assessment exercise. We wished to determine the students' and tutors' satisfaction with this structured approach as compared with the more traditional tutorial experienced in other courses at HMS. Methods: For the first 4 years of the course, students (n = 160) were surveyed concerning their impressions of the quality of the structured approach in comparison with the traditional tutorial. In addition, they were surveyed concerning the cornerstone presentations and the self-assessment exercise. Tutors (n = 10) who had taught in both the traditional and structured tutorial formats were surveyed about their impressions of student performance as well as their own enjoyment in the structured format. Results: Students and tutors found the structured approach superior to the previous method. Both groups noted increased student preparation, participation, and accountability. Tutors preferred teaching in the structured format. Conclusions: The structured approach increased student accountability, preparation, and participation. Students and tutors preferred this tutorial experience over the previous approach. C1 [Cardozo, David Lopes] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [White, Benjamin] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Cardozo, DL (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. EM David_Cardozo@hms.harvard.edu NR 25 TC 2 Z9 2 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PY 2012 VL 34 IS 11 BP E763 EP E771 DI 10.3109/0142159X.2012.691187 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 049UV UT WOS:000312009800007 PM 22861351 ER PT B AU Alio, JL Llorens, DPP Pomares, ES Amparo, F Garrido, LJM AF Alio, Jorge L. Pinero Llorens, David P. Sala Pomares, Esperanza Amparo, Francisco Moreno Garrido, Luis J. BE Pallikaris, IG Plainis, S Charman, WN TI PRESBYOPIC LASIK SO PRESBYOPIA: ORIGIN, EFFECTS, AND TREATMENT LA English DT Article; Book Chapter ID ADVANCED-SURFACE ABLATION; TECHNOVISION PRESBYLASIK; EXCIMER-LASER; HYPEROPIA; PLATFORM C1 [Alio, Jorge L.; Moreno Garrido, Luis J.] Miguel Hernandez Univ, Alicante, Spain. [Alio, Jorge L.] Vissum Corp, Alicante, Spain. [Amparo, Francisco] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv,Dept Ophthalmol, Boston, MA USA. [Pinero Llorens, David P.] Univ Alicante, Dept Opt Pharmacol & Anat, E-03080 Alicante, Spain. RP Alio, JL (reprint author), Miguel Hernandez Univ, Alicante, Spain. RI Moreno-Garrido, Luis/N-5831-2014 OI Moreno-Garrido, Luis/0000-0002-2592-0829 NR 17 TC 1 Z9 1 U1 0 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-026-9 PY 2012 BP 183 EP 190 PG 8 WC Ophthalmology SC Ophthalmology GA BCZ73 UT WOS:000312228600021 ER PT S AU Santos, ICT Gazelle, GS Rocha, LA Tavares, JMRS AF Santos, Isa C. T. Gazelle, G. Scott Rocha, Luis A. Tavares, Joao Manuel R. S. BE Jobbagy, A TI Development of Medical Devices: Advantages of a Methodic Approach SO 5TH EUROPEAN CONFERENCE OF THE INTERNATIONAL FEDERATION FOR MEDICAL AND BIOLOGICAL ENGINEERING, PTS 1 AND 2 SE IFMBE Proceedings LA English DT Proceedings Paper CT 5th European Conference of the International Federation for Medical and Biological Engineering CY SEP 14-18, 2011 CL Budapest, HUNGARY DE Product development; Optimization; Decision; Review; Public health regulation and supervision AB It is possible to advocate that, as far as complexity is concerned, the medical devices sector is comparable to the aviation and nuclear industries. Some of the arguments used are the broad definition of the term "medical device", the multiplicity of regulations and the nature of the relation between manufacturers and users. In such environment, the uncertainty associated to the development of novel devices is high and justifies the use of dedicated methodologies. In general, the application of product development methodologies helps to reduce the duration of the tasks, optimize the available resources and obtain products and/or services that please customers. In the case of medical devices, the authors believe that resorting to such methodologies is crucial to overcome the industry's complexity without losing competitiveness. The product development process involves the following steps: identification of an opportunity, voice of the customer, concept development, design, test and validation and launch. This paper describes each one of the aforementioned stages and suggests adaptations to the healthcare sector. C1 [Santos, Isa C. T.; Tavares, Joao Manuel R. S.] Univ Porto, Fac Engn, Inst Mech Engn & Ind Management, Rua Dr Roberto Frias S-N, P-4200465 Oporto, Portugal. [Gazelle, G. Scott] Harvard Med Sch, Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, Boston, MA USA. [Rocha, Luis A.] Univ Minho, Inst Polymers & Composite, P-4719 Braga, Portugal. RP Santos, ICT (reprint author), Univ Porto, Fac Engn, Inst Mech Engn & Ind Management, Rua Dr Roberto Frias S-N, P-4200465 Oporto, Portugal. EM isa.santos@fe.up.pt RI Rocha, Luis/A-6676-2013; Tavares, Joao/M-5305-2013 OI Rocha, Luis/0000-0001-8184-8801; Tavares, Joao/0000-0001-7603-6526 FU FCT - Fundacao para a Ciencia e Tecnologia, in Portugal [SFRH/BD/42967/2008]; FCT [MITPt/EDAM-EMD/0007/2008] FX The first author wishes to thank FCT - Fundacao para a Ciencia e Tecnologia, in Portugal, for the financial support provided by the PhD grant SFRH/BD/42967/2008. This work is partially supported by FCT under the project MITPt/EDAM-EMD/0007/2008. NR 8 TC 0 Z9 0 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1680-0737 BN 978-3-642-23507-8 J9 IFMBE PROC PY 2012 VL 37 BP 1144 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BCP21 UT WOS:000310938200296 ER PT J AU Bautista, PA Yagi, Y AF Bautista, Pinky A. Yagi, Yukako TI Multispectral enhancement method to increase the visual differences of tissue structures in stained histopathology images SO ANALYTICAL CELLULAR PATHOLOGY LA English DT Article DE Multispectral; enhancement; visualization; multispectral; detection; histopathology ID SPECTRAL TRANSMITTANCE; QUANTIFICATION; CLASSIFICATION AB In this paper we proposed a multispectral enhancement scheme in which the spectral colors of the stained tissue-structure of interest and its background can be independently modified by the user to further improve their visualization and color discrimination. The colors of the background objects are modified by transforming their N-band spectra through an NxN transformation matrix, which is derived by mapping the representative samples of their original spectra to the spectra of their target colors using least mean square method. On the other hand, the color of the tissue structure of interest is modified by modulating the transformed spectra with the sum of the pixel's spectral residual-errors at specific bands weighted through an NxN weighting matrix; the spectral error is derived by taking the difference between the pixel's original spectrum and its reconstructed spectrum using the first M dominant principal component vectors in principal component analysis. Promising results were obtained on the visualization of the collagen fiber and the non-collagen tissue structures, e. g., nuclei, cytoplasm and red blood cells (RBC), in a hematoxylin and eosin (H&E) stained image. C1 [Bautista, Pinky A.; Yagi, Yukako] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Bautista, PA (reprint author), MGH Pathol Imaging & Commun Technol PICT Ctr, 101 Merrimac St,Suite 820, Boston, MA 02114 USA. EM pbautista@partners.org FU Olympus, Inc. Japan FX This work is supported in part by Olympus, Inc. Japan. NR 23 TC 1 Z9 1 U1 1 U2 6 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 2210-7177 J9 ANAL CELL PATHOL JI Anal. Cell. Pathol. PY 2012 VL 35 IS 5-6 BP 407 EP 420 DI 10.3233/ACP-2012-0069 PG 14 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 045DS UT WOS:000311675800007 PM 22935779 ER PT J AU Mogabgab, O Giugliano, RP Sabatine, MS Cannon, CP Mohanavelu, S Wiviott, SD Antman, EM Braunwald, E AF Mogabgab, Owen Giugliano, Robert P. Sabatine, Marc S. Cannon, Christopher P. Mohanavelu, Satishkumar Wiviott, Stephen D. Antman, Elliott M. Braunwald, Eugene TI Circadian Variation in Patient Characteristics and Outcomes in ST-Segment Elevation Myocardial Infarction SO CHRONOBIOLOGY INTERNATIONAL LA English DT Article DE Fibrinolysis; Lytic resistance; Morning myocardial infarction ID OBSTRUCTIVE SLEEP-APNEA; UNFRACTIONATED HEPARIN; INTRAVENOUS NPA; SYMPTOM ONSET; TRIAL; CHRONOBIOLOGY; FIBRINOLYSIS; METAANALYSIS; ENOXAPARIN; PREVENTION AB A morning peak in ST-segment elevation myocardial infarction (STEMI) has been described. The authors explored the relationship between variation of symptom onset, patient characteristics, and outcomes in two worldwide fibrinolytic trials. A total of 35 492 patients with STEMI were grouped into 8-h intervals by time of symptom onset: early (06: 00 to 13: 59 h), late-day (14: 00 to 21: 59 h), overnight (22: 00 to 05: 59 h). The authors correlated timing with patient characteristics and outcomes (adjusted for thrombolysis in myocardial infarction [TIMI] risk score) first in InTIME II-TIMI 17 trial (N = 15 031), and confirmed in the ExTRACT-TIMI 25 trial (N = 20 461). Timing was similar in the derivation (early 49%, late-day 30%, and overnight 21%; p < .001) and validation set (48%, 31%, and 21%, respectively; p <.001). Some patient characteristics consistently varied with time of symptom onset. Patients in the early cohort were older with poorer renal function. The late-day group had more smokers with higher initial heart rate and systolic blood pressure. Those with overnight symptom onset had higher rates of obesity, prior myocardial infarction, and treatment delays. Prior use of aspirin and beta-blockers was also highest in the overnight group. Relative to the early cohort, adjusted mortality was higher with late-day onset (derivation odds ratio [OR]: 1.19, p=.04; validation OR: 1.18, p=.01), but there was no excess in mortality overnight compared with early (derivation OR:.97, p=.72; validation OR: 1.01, p=.90). Composite endpoints followed similar patterns. This study indicates that circadian patterns in onset of STEMI continue to exist with patient characteristics differing by time of day. Despite a potential physiologic resistance to morning thrombolysis, outcomes were best in the early cohort, intermediate overnight, and worst with late-day symptom onset. Efforts to reduce smoking and improve control of blood pressure could reduce the number of patients with late-day onset of STEMI who experience the worst outcomes. (Author correspondence: owen@mogabgab.com) C1 [Mogabgab, Owen] Univ Texas SW Med Sch, Div Cardiol, Dallas, TX 75390 USA. [Giugliano, Robert P.; Sabatine, Marc S.; Cannon, Christopher P.; Mohanavelu, Satishkumar; Wiviott, Stephen D.; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Giugliano, Robert P.; Sabatine, Marc S.; Cannon, Christopher P.; Mohanavelu, Satishkumar; Wiviott, Stephen D.; Antman, Elliott M.; Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA. RP Mogabgab, O (reprint author), Univ Texas SW Med Sch, Div Cardiol, 5323 Harry Hines Blvd,MC 8830, Dallas, TX 75390 USA. EM owen@mogabgab.com FU Sanofi-Aventis; Bristol-Myers Squibb FX Drs. Giugliano and Brauwald receive research grant support from Sanofi-Aventis and Bristol-Myers Squibb and Dr. Giugliano receives consulting fees and honoraria from Bristol-Myers Squibb and honoraria from Sanofi-Aventis. NR 26 TC 6 Z9 7 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0742-0528 J9 CHRONOBIOL INT JI Chronobiol. Int. PY 2012 VL 29 IS 10 BP 1390 EP 1396 DI 10.3109/07420528.2012.728658 PG 7 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 047JU UT WOS:000311837200012 PM 23131034 ER PT S AU Henson, JW Gonzalez, RG AF Henson, John W. Gonzalez, R. Gilberto BE Grisold, W Soffietti, R TI Neuroimaging SO NEURO-ONCOLOGY, PT I SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID CONTRAST-ENHANCED MR; MAGNETIC-RESONANCE-SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; HIGH-GRADE GLIOMAS; BRAIN METASTASES; IMAGING FINDINGS; TUMOR; CT; HISTOPATHOLOGY; FEATURES C1 [Henson, John W.] Swedish Neurosci Inst, Ivy Ctr Adv Brain Tumor Treatment, Dept Neurooncol, Seattle, WA 98040 USA. [Gonzalez, R. Gilberto] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol,Dept Radiol, Boston, MA USA. RP Henson, JW (reprint author), Swedish Neurosci Inst, Ivy Ctr Adv Brain Tumor Treatment, Dept Neurooncol, Seattle, WA 98040 USA. EM john.henson@swedish.org NR 57 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-44-453495-8 J9 HAND CLINIC PY 2012 VL 104 BP 109 EP 126 PG 18 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA BCX75 UT WOS:000311893800010 PM 22230438 ER PT S AU Chi, AS Wen, PY AF Chi, Andrew S. Wen, Patrick Y. BE Grisold, W Soffietti, R TI Inhibiting angiogenesis in malignant gliomas SO NEURO-ONCOLOGY, PT I SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; HIGH-GRADE GLIOMAS; TYROSINE KINASE INHIBITOR; METASTATIC COLORECTAL-CANCER; VASCULAR-PERMEABILITY FACTOR; HUMAN GLIOBLASTOMA CELLS; NECROSIS-FACTOR-ALPHA; LOW-DOSE CHEMOTHERAPY; PLASMINOGEN-ACTIVATOR RECEPTOR C1 [Wen, Patrick Y.] Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. [Chi, Andrew S.] Massachusetts Gen Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02114 USA. [Chi, Andrew S.] Massachusetts Gen Hosp, Dept Neurol, Div Hematol Oncol, Boston, MA 02114 USA. [Chi, Andrew S.; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Shields Warren 430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org NR 332 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-44-453495-8 J9 HAND CLINIC PY 2012 VL 104 BP 279 EP 308 PG 30 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA BCX75 UT WOS:000311893800021 PM 22230449 ER PT J AU Mueser, KT Gottlieb, JD Cather, C Glynn, SM Zarate, R Smith, MF Clark, RE Wolfe, R AF Mueser, Kim T. Gottlieb, Jennifer D. Cather, Corrine Glynn, Shirley M. Zarate, Roberto Smith, Melinda F. Clark, Robin E. Wolfe, Rosemarie TI Antisocial personality disorder in people with co-occurring severe mental illness and substance use disorders: clinical, functional, and family relationship correlates SO PSYCHOSIS-PSYCHOLOGICAL SOCIAL AND INTEGRATIVE APPROACHES LA English DT Article DE bipolar disorder; cannabis; carers; family therapy; families; personality disorder ID CONDUCT DISORDER; BIPOLAR DISORDER; DUAL DISORDERS; SCHIZOPHRENIA; ABUSE; SCALE; INTERVENTION; PSYCHOPATHOLOGY; METAANALYSIS; COMORBIDITY AB Antisocial personality disorder (ASPD) is an important correlate of substance abuse severity in the addiction population and in people with co-occurring serious mental illness and addiction. Because family members often provide vital supports to relatives with co-occurring disorders, this study explored the correlates of ASPD in 103 people with co-occurring disorders (79% schizophrenia-schizoaffective, 21% bipolar disorder) in high contact with relatives participating in a family intervention study. Clients with ASPD were more likely to have bipolar disorder and to have been married, but less likely to have graduated from high school. ASPD was associated with more severe drug abuse and depression, worse functioning, and less planning-based social problem solving. The relatives of clients with ASPD also reported less planning-based problem solving, worse attitudes towards the client, and worse mental health functioning. Client ASPD was associated with less long-term exposure to family intervention. The findings suggest that clients with ASPD in addition to co-occurring disorders are a particularly disadvantaged group with greater illness severity, more impaired functioning, and more strained family relationships. These difficulties may pose special challenges to delivering family intervention for this group. C1 [Mueser, Kim T.] Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. [Gottlieb, Jennifer D.] Boston Univ, Dept Occupat Therapy, Boston, MA 02215 USA. [Cather, Corrine] Harvard Univ, Sch Med, Dept Psychiat, Schizophrenia Program,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Glynn, Shirley M.; Zarate, Roberto] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Smith, Melinda F.; Wolfe, Rosemarie] Dartmouth Med Sch, Dartmouth Psychiat Res Ctr, Dept Psychiat, Concord, NH USA. [Clark, Robin E.] Univ Massachusetts, Sch Med, Ctr Hlth Policy & Res, Shrewsbury, MA USA. RP Mueser, KT (reprint author), Boston Univ, Ctr Psychiat Rehabil, Boston, MA 02215 USA. EM kim.t.Mueser@dartmouth.edu FU NIMH NIH HHS [R01 MH062629, R01 MH062629-05] NR 45 TC 9 Z9 9 U1 7 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1752-2439 J9 PSYCHOSIS JI Psychosis PY 2012 VL 4 IS 1 BP 52 EP 62 DI 10.1080/17522439.2011.639901 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 044OS UT WOS:000311630600006 PM 22389652 ER PT J AU Bansal, N Whooley, MA Regan, M McCulloch, CE Ix, JH Epel, E Blackburn, E Lin, J Hsu, CY AF Bansal, Nisha Whooley, Mary A. Regan, Mathilda McCulloch, Charles E. Ix, Joachim H. Epel, Elissa Blackburn, Elizabeth Lin, Jue Hsu, Chi-yuan TI Association between Kidney Function and Telomere Length: The Heart and Soul Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Kidney; Chronic kidney disease; Telomere ID CORONARY-ARTERY-DISEASE; CYSTATIN-C; CARDIOVASCULAR HEALTH; HEMODIALYSIS-PATIENTS; MONONUCLEAR-CELLS; MORTALITY; CREATININE; FAILURE; EVENTS; RISK AB Background: Telomere attrition is a novel risk factor for cardiovascular disease. Studies of telomere length in relation to kidney function are limited. We explored the association of kidney function with telomere length and telomere shortening. Methods: The Heart and Soul Study is a longitudinal study of patients with stable coronary heart disease. Measures of baseline kidney function included: serum creatinine, creatinine-derived estimated glomerular filtration rate (eGFR(CKD-EPI)), 24-hour urine measured creatinine clearance, cystatin C, cystatin C-derived estimated glomerular filtration rate (eGFRcys) and urine albumin to creatinine ratio. Telomere length was measured from peripheral blood leukocytes at baseline (n = 954) and 5 years later (n = 608). Linear regression models were used to test the association of kidney function with (i) baseline telomere length and (ii) change in telomere length over 5 years. Results: At baseline, mean eGFR(CKD-EPI) was 72.6 (+/- 21.5) ml/min/1.73 m(2), eGFRcys was 71.0 (+/- 23.1) ml/min/1.73 m(2) and ACR was 8.6 (+/- 12.3) mg/g. Only lower baseline eGFR(CKD-EPI) was associated with shorter baseline telomere length (9.1 (95% CI 1.2-16.9) fewer base pairs for every 5 ml/min/1.73 m(2) lower eGFR(CKD-EPI)). Lower baseline eGFR(CKD-EPI) (and all other measures of kidney function) predicted more rapid telomere shortening (10.8 (95% CI 4.3-17.3) decrease in base pairs over 5 years for every 5 ml/min/1.73 m(2) lower eGFR(CKD-EPI)). After adjustment for age, these associations were no longer statistically significant. Conclusions: In patients with coronary heart disease, reduced kidney function is associated with (i) shorter baseline telomere length and (ii) more rapid telomere shortening over 5 years; however, these associations are entirely explained by older age. Copyright (c) 2012 S. Karger AG, Basel C1 [Bansal, Nisha] Univ Calif San Francisco, Div Nephrol, Dept Med, San Francisco, CA 94143 USA. [Whooley, Mary A.; McCulloch, Charles E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Epel, Elissa] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Blackburn, Elizabeth; Lin, Jue] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. [Whooley, Mary A.; Regan, Mathilda] San Francisco VA Med Ctr, San Francisco, CA USA. [Ix, Joachim H.] Univ Calif San Diego, Nephrol Sect, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Med, Div Nephrol, San Diego, CA 92103 USA. [Ix, Joachim H.] Univ Calif San Diego, Dept Family & Preventat Med, Div Preventat Med, San Diego, CA 92103 USA. RP Bansal, N (reprint author), Univ Calif San Francisco, Div Nephrol, Dept Med, 521 Parnassus Ave,Box 0532, San Francisco, CA 94143 USA. EM nisha.bansal@ucsf.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK088865, K24 DK92291]; National Heart Lung and Blood Institute [1R01HL096851]; American Heart Association Fellow-to-Faculty Transition Award; Sandra Daugherty Foundation; Department of Veterans Affairs; American Federation of Aging Research; Robert Wood Johnson Foundation; Nancy Kirwan Heart Research Fund; Ischemia Research and Education Foundation; NHLBI [R01 HL079235] FX This study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK088865 to N.B. and K24 DK92291 to C.H.), National Heart Lung and Blood Institute (1R01HL096851) (J.H.I.), an American Heart Association Fellow-to-Faculty Transition Award (J.H.I.), and an award from the Sandra Daugherty Foundation (J.H.I.). The Heart and Soul Study was funded by the Department of Veterans Affairs, American Federation of Aging Research, Robert Wood Johnson Foundation, Nancy Kirwan Heart Research Fund, Ischemia Research and Education Foundation, and the NHLBI (R01 HL079235). NR 25 TC 10 Z9 11 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2012 VL 36 IS 5 BP 405 EP 411 DI 10.1159/000343495 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 042SZ UT WOS:000311492600002 PM 23108000 ER PT J AU Friedman, AN Yu, ZS Tabbey, R Denski, C Tamez, H Wenger, J Thadhani, R Li, Y Watkins, BA AF Friedman, Allon N. Yu, Zhangsheng Tabbey, Rebeka Denski, Cheryl Tamez, Hector Wenger, Julia Thadhani, Ravi Li, Yong Watkins, Bruce A. TI Low Blood Levels of Long-Chain n-3 Polyunsaturated Fatty Acids in US Hemodialysis Patients: Clinical Implications SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Omega-3; Fatty acids; Hemodialysis; Cardiovascular; Nutrition ID ADIPOSE-TISSUE; FISH-OIL; CARDIOVASCULAR-DISEASE; TERM HEMODIALYSIS; PLASMA; SERUM; OMEGA-3-FATTY-ACIDS; EVENTS; RISK; SUPPLEMENTATION AB Background: Cardioprotective and other clinical benefits of long-chain n-3 polyunsaturated fatty acids (PUFA) are inversely related to dietary intake and hence blood content. We therefore investigated, in the first study of its kind, the blood content and distribution of these fatty acids in a large representative population of US hemodialysis patients. Methods: Frozen sera were obtained from 400 individuals who were part of a large, contemporary, representative cohort of US incident hemodialysis patients. Long-chain n-3 PUFA were measured in total serum lipids and in the neutral and polar serum fractions using gas chromatography and solid phase extraction techniques. Mean long-chain n-3 PUFA levels were compared to levels in other dialysis and nondialysis populations from published reports. Results: The study population was qualitatively similar to the overall US hemodialysis population in terms of major clinical characteristics. Long-chain n-3 PUFA were present in the serum polar fraction, with essentially none being detected in the neutral fraction ( p < 0.0001 for polar vs. neutral fractions forall three long-chain n-3 PUFA). Mean serum long-chain n-3 PUFA levels (weight percent (+/- SD): total 1.55 +/- 0.95, polar 3.99 +/- 1.45) were low compared to nondialysis and most other non-US hemodialysis cohorts. Conclusions: While US hemodialysis patients have a blood distribution of longchain n-3 PUFA that is similar to that in the general population, blood content is among the lowest recorded in the medical literature. This has implications for renal dietary recommendations and makes US patients an ideal group for testing the clinical effects of long-chain n-3 PUFA supplementation. Copyright c 2012 S. Karger AG, Basel C1 [Friedman, Allon N.] Indiana Univ Sch Med, Dept Med, Div Nephrol, Indianapolis, IN USA. [Yu, Zhangsheng; Tabbey, Rebeka; Denski, Cheryl] Indiana Univ Sch Med, Dept Biostat, Indianapolis, IN USA. [Tamez, Hector; Wenger, Julia; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Li, Yong; Watkins, Bruce A.] Univ Connecticut, Dept Nutr Sci, Lipid Chem & Mol Biol Lab, Storrs, CT USA. RP Friedman, AN (reprint author), 535 Barnhill Dr,RT 150R, Indianapolis, IN 46202 USA. EM allfried@iupui.edu FU National Institutes of Health [DK084403, DK094872, HL112746]; National Kidney Foundation FX A.N.F. and B.A.W. were supported by funding from the National Institutes of Health (DK084403) and the National Kidney Foundation. R. T. is supported by funding from the National Institutes of Health (DK094872, HL112746). Some of the data described herein were presented at the 2012 International Society for Renal Metabolism and Nutrition meeting. NR 37 TC 8 Z9 8 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2012 VL 36 IS 5 BP 451 EP 458 DI 10.1159/000343741 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 042SZ UT WOS:000311492600009 PM 23128302 ER PT J AU Hui, JY Choi, JWJ Mount, DB Zhu, YY Zhang, YQ Choi, HK AF Hui, Janet Y. Choi, Jee Woong J. Mount, David B. Zhu, Yanyan Zhang, Yuqing Choi, Hyon K. TI The independent association between parathyroid hormone levels and hyperuricemia: a national population study SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID PURINE-RICH FOODS; URIC-ACID; PRIMARY HYPERPARATHYROIDISM; POSTMENOPAUSAL WOMEN; SERUM URATE; OSTEOPOROSIS; GOUT; TERIPARATIDE; PROTEIN; DISEASE AB Introduction: Increased frequencies of hyperuricemia and gout have been associated with primary hyperparathyroidism, and recent clinical trials of parathyroid hormone (PTH) have reported hyperuricemic adverse events. We evaluated the potential population impact of PTH on serum uric acid (SUA) levels by using a nationally representative sample of United States adults. Methods: By using data from 8,316 participants aged 18 years and older in the National Health and Nutrition Examination Survey 2003 to 2006, we examined the relation between serum PTH and SUA levels with weighted linear regression. Additionally, we examined the relation with hyperuricemia by using weighted logistic regression. Results: SUA levels increased with increasing serum PTH concentration. After adjusting for age, sex, dietary factors, glomerular filtration rate (GFR), and other potentially related biomarkers (calcium, phosphorus, alkaline-phosphatase, 25-hydroxyvitamin D), the SUA level differences from the bottom (referent) to top quintiles of serum PTH levels were 0, 8, 13, 14, and 19 mu M (95% CI, 12 to 26; P for trend, < 0.001). These estimates were larger among renally impaired individuals (multivariate SUA difference between the extreme quintiles of PTH, 26 versus 15 mu M among those with GFR >= 60 versus < 60 ml/min per 1.73 m(2), respectively) (P for interaction = 0.004). The odds of hyperuricemia by various definitions increased with increasing PTH levels as well (multivariate P values for trend, < 0.05). Conclusions: These nationally representative data indicate that serum PTH levels are independently associated with serum uric acid levels and the frequency of hyperuricemia at the population level. C1 [Hui, Janet Y.; Choi, Jee Woong J.; Zhu, Yanyan; Zhang, Yuqing; Choi, Hyon K.] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02118 USA. [Mount, David B.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Renal Div,Dept Med, Boston, MA 02115 USA. [Mount, David B.] VA Boston Healthcare Syst, Div Nephrol, Boston, MA 02130 USA. [Choi, Hyon K.] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA. RP Choi, HK (reprint author), Boston Univ, Sch Med, Clin Epidemiol Unit, 650 Albany St,Suite 200, Boston, MA 02118 USA. EM hchoius@bu.edu OI Zhang, Yuqing/0000-0001-7954-1149 FU National Institutes of Health [R01AR056291, P60AR047785] FX This work was supported in part by grants from the National Institutes of Health (R01AR056291, P60AR047785). NR 26 TC 17 Z9 18 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2012 VL 14 IS 2 AR R56 DI 10.1186/ar3769 PG 6 WC Rheumatology SC Rheumatology GA 036KX UT WOS:000311025900015 PM 22405053 ER PT B AU Horsley, MB Rhee, DJ AF Horsley, Michael B. Rhee, Douglas J. BE Kahook, MY TI COMBINED PHACOEMULSIFICATION AND TRABECTOME SO ESSENTIALS OF GLAUCOMA SURGERY LA English DT Article; Book Chapter ID OPEN-ANGLE GLAUCOMA; TRABECULECTOMY C1 [Rhee, Douglas J.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Rhee, Douglas J.] Harvard Univ, Sch Med, Boston, MA USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-012-2 PY 2012 BP 149 EP 152 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BCO13 UT WOS:000310814200017 ER PT B AU Ledoux, DM Johnston, S Walton, DS AF Ledoux, Danielle M. Johnston, Suzanne Walton, David S. BE Kahook, MY TI ANGLE SURGERY GONIOTOMY AND TRABECULOTOMY SO ESSENTIALS OF GLAUCOMA SURGERY LA English DT Article; Book Chapter C1 [Ledoux, Danielle M.; Walton, David S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Ledoux, Danielle M.; Johnston, Suzanne] Childrens Hosp Boston, Boston, MA USA. RP Ledoux, DM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE ROAD, THOROFARE, NJ 08086-9447 USA BN 978-1-61711-012-2 PY 2012 BP 261 EP 272 PG 12 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA BCO13 UT WOS:000310814200031 ER PT J AU Bharadwaj, PR Verdile, G Barr, RK Gupta, V Steele, JW Lachenmayer, ML Yue, ZY Ehrlich, ME Petsko, G Ju, SL Ringe, D Sankovich, SE Caine, JM Macreadie, IG Gandy, S Martins, RN AF Bharadwaj, Prashant R. Verdile, Giuseppe Barr, Renae K. Gupta, Veer Steele, John W. Lachenmayer, M. Lenard Yue, Zhenyu Ehrlich, Michelle E. Petsko, Gregory Ju, Shulin Ringe, Dagmar Sankovich, Sonia E. Caine, Joanne M. Macreadie, Ian G. Gandy, Sam Martins, Ralph N. TI Latrepirdine (Dimebon (TM)) Enhances Autophagy and Reduces Intracellular GFP-A beta(42) Levels in Yeast SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid-beta; autophagy; latrepirdine; yeast model ID AMYLOID-BETA PEPTIDE; IMMUNODEFICIENCY-VIRUS TYPE-1; HUNTINGTONS-DISEASE MODELS; GREEN FLUORESCENT PROTEIN; SMALL-MOLECULE ENHANCERS; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; NONSPECIFIC AUTOPHAGY; NEURONAL CELLS; IN-VITRO AB Latrepirdine (Dimebon (TM)), an anti-histamine, has shown some benefits in trials of neurodegenerative diseases characterized by accumulation of aggregated or misfolded protein such as Alzheimer's disease (AD) and has been shown to promote the removal of alpha-synuclein protein aggregates in vivo. An important pathway for removal of aggregated or misfolded proteins is the autophagy-lysosomal pathway, which has been implicated in AD pathogenesis, and enhancing this pathway has been shown to have therapeutic potential in AD and other proteinopathies. Here we use a yeast model, Saccharomyces cerevisiae, to investigate whether latrepirdine can enhance autophagy and reduce levels of amyloid-beta (A beta)(42) aggregates. Latrepirdine was shown to upregulate yeast vacuolar (lysosomal) activity and promote transport of the autophagic marker (Atg8) to the vacuole. Using an in vitro green fluorescent protein (GFP) tagged A beta yeast expression system, we investigated whether latrepirdine-enhanced autophagy was associated with a reduction in levels of intracellular GFP-A beta(42). GFP-A beta(42) was localized into punctate patterns compared to the diffuse cytosolic pattern of GFP and the GFP-A beta(42) (19 : 34), which does not aggregate. In the autophagy deficient mutant (Atg8 Delta), GFP-A beta(42) showed a more diffuse cytosolic localization, reflecting the inability of this mutant to sequester GFP-A beta(42). Similar to rapamycin, we observed that latrepirdine significantly reduced GFP-A beta(42) in wild-type compared to the Atg8 Delta mutant. Further, latrepirdine treatment attenuated A beta(42)-induced toxicity in wild-type cells but not in the Atg8 Delta mutant. Together, our findings provide evidence for a novel mechanism of action for latrepirdine in inducing autophagy and reducing intracellular levels of GFP-A beta(42). C1 [Bharadwaj, Prashant R.; Verdile, Giuseppe; Barr, Renae K.; Gupta, Veer; Martins, Ralph N.] Edith Cowan Univ, Sch Med Sci, Ctr Excellence Alzheimers Dis Res & Care, Churchlands, WA 6018, Australia. [Verdile, Giuseppe; Martins, Ralph N.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Crawley, WA, Australia. [Verdile, Giuseppe; Steele, John W.; Martins, Ralph N.] Hollywood Private Hosp, Sir James McCusker Alzheimers Dis Res Unit, Nedlands, WA, Australia. [Bharadwaj, Prashant R.; Sankovich, Sonia E.; Caine, Joanne M.; Macreadie, Ian G.] CSIRO Preventat Hlth Flagship, Mat Sci & Engn, Melbourne, Vic, Australia. [Lachenmayer, M. Lenard; Yue, Zhenyu; Ehrlich, Michelle E.; Gandy, Sam] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Yue, Zhenyu] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Steele, John W.; Gandy, Sam] Mt Sinai Sch Med, Alzheimers Dis Res Ctr, New York, NY USA. [Steele, John W.; Gandy, Sam] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Ehrlich, Michelle E.] Mt Sinai Sch Med, Dept Paediat, New York, NY USA. [Gandy, Sam] James J Peters VA Med Ctr, Bronx, NY USA. [Lachenmayer, M. Lenard] Univ Bonn, Dept Neurol, Bonn, Germany. [Petsko, Gregory; Ju, Shulin; Ringe, Dagmar] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Biochem & Chem, Waltham, MA 02254 USA. [Macreadie, Ian G.] RMIT Univ, Sch Appl Sci, Bundoora, Vic, Australia. RP Martins, RN (reprint author), Hollywood Med Ctr, Suite 22,85 Monash Ave, Nedlands, WA 6009, Australia. EM r.martins@ecu.edu.au RI Macreadie, Ian/F-5997-2010 OI Macreadie, Ian/0000-0001-5335-7220 FU NHMRC [APP1009295]; McCusker Alzheimer's Research Foundation; Cure Alzheimer's Fund; NIH 12 [AG10491]; Fidelity Biosciences Research Initiative; Deutsche Forschungsgemeinschaft; NIGMS [T32M062754]; Medivation, Inc.; Amicus Pharmaceuticals FX The authors acknowledge the generous support of NH&MRC (APP1009295 to RM, GV, SG), McCusker Alzheimer's Research Foundation (RM, GV), Cure Alzheimer's Fund (SG) and NIH 12 (AG10491 to SG), and the Fidelity Biosciences Research Initiative (SJ, JL, DR, GAP), Deutsche Forschungsgemeinschaft (MLL). JWS is a trainee in the Integrated Pharmacological Sciences Training Program supported by grant T32M062754 from the NIGMS. MEE holds research grant support from Medivation, Inc. SG holds research grant support from Amicus Pharmaceuticals and is a consultant to the Pfizer-Janssen Alzheimer's Immunotherapy Alliance. NR 79 TC 25 Z9 25 U1 2 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 32 IS 4 BP 949 EP 967 DI 10.3233/JAD-2012-120178 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 039EP UT WOS:000311227200008 PM 22903131 ER PT J AU Eastman, KL Lutton, MC Raugi, GJ Sakamoto, MR McDowell, JA McFarland, LV Reiber, GE AF Eastman, Kristin L. Lutton, Marie C. Raugi, Gregory J. Sakamoto, Mandy R. McDowell, Jennifer A. McFarland, Lynne V. Reiber, Gayle E. TI A teledermatology care management protocol for tracking completion of teledermatology recommendations SO JOURNAL OF TELEMEDICINE AND TELECARE LA English DT Article ID OUTCOMES AB In July 2009 we implemented a 3-year store-and-forward teledermatology project to provide dermatology care to veterans living in rural and underserved areas of the US Pacific Northwest. We also developed a follow-up protocol and tracking system. Information about all completed teledermatology consultations was entered into a database, and major procedures and select medications were tracked. In the first 21 months, 8202 dermatology conditions in 5232 veterans were treated and 3370 major procedures carried out. Ninety-five percent of conditions were associated with no more than two teledermatology consultations, and no condition required more than ten consultations. In total, 1454 conditions were reviewed for clinical pathological correlation, and in 310 (21%) there was a subsequent clinical pathological correlation conference, resulting in a change in final diagnosis for 93 conditions. The follow-up was important in ensuring high quality patient care. C1 [Eastman, Kristin L.; Lutton, Marie C.; Sakamoto, Mandy R.; McDowell, Jennifer A.; McFarland, Lynne V.; Reiber, Gayle E.] VA Puget Sound Healthcare Syst, Hlth Serv R&D, Seattle, WA 98101 USA. [Eastman, Kristin L.; Raugi, Gregory J.] Univ Washington, Sch Med, Seattle, WA USA. [Eastman, Kristin L.; Reiber, Gayle E.] VA Puget Sound Healthcare Syst, Rehabil Res & Dev, Seattle, WA 98101 USA. [Raugi, Gregory J.] VA Puget Sound Healthcare Syst, Dermatol Sect, Hosp & Specialty Med Serv, Seattle, WA 98101 USA. [Reiber, Gayle E.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP McFarland, LV (reprint author), VA Puget Sound Healthcare Syst, Hlth Serv R&D, Metropolitan Pk W,1100 Olive Way,1400, Seattle, WA 98101 USA. EM lynne.mcfarland@va.gov FU US Department of Veterans Affairs; VISN 20 Office of Rural Health Services; VA Health Services Research and Development; [RCS 98-353] FX This work was funded by the US Department of Veterans Affairs, VISN 20 Office of Rural Health Services, VA Health Services Research and Development, and the Career Scientist Award (RCS 98-353) of Dr Gayle Reiber. The views expressed in this article do not necessarily reflect those of the Department of Veterans Affairs or the United States Government. NR 14 TC 4 Z9 4 U1 0 U2 2 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1357-633X J9 J TELEMED TELECARE JI J. Telemed. Telecare PY 2012 VL 18 IS 7 BP 374 EP 378 DI 10.1258/jtt.2012.120417 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 043DE UT WOS:000311522300002 PM 23086980 ER PT B AU Randolph, GW Kulcsar, MAV Brandao, LG AF Randolph, Gregory W. Kulcsar, Marco A. V. Brandao, Lenine Garcia BE Cernea, CR TI New Aspects of Nerve Monitoring in Thyroid and Parathyroid Surgery SO PEARLS AND PITFALLS IN HEAD AND NECK SURGERY: PRACTICAL TIPS TO MINIMIZE COMPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID RECURRENT LARYNGEAL NERVE C1 [Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Thyroid Surg Div, Boston, MA USA. [Kulcsar, Marco A. V.] Head & Neck Surg Canc Inst Sao Paulo ICESP, Sao Paulo, Brazil. [Brandao, Lenine Garcia] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. RP Randolph, GW (reprint author), 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu RI Brandao, Lenine/J-5334-2013; Kulcsar, Marco/L-8779-2013 OI Kulcsar, Marco/0000-0002-4751-0476 NR 7 TC 0 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND BN 978-3-8055-9972-6 PY 2012 BP 6 EP 7 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA BCO08 UT WOS:000310813700004 ER PT B AU Deschler, DG Haughey, BH Rocco, JW AF Deschler, Daniel G. Haughey, Bruce H. Rocco, James W. BE Cernea, CR TI Influence of Human Papillomavirus Status on the Management of Oropharyngeal Tumors SO PEARLS AND PITFALLS IN HEAD AND NECK SURGERY: PRACTICAL TIPS TO MINIMIZE COMPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID CLINICAL-IMPLICATIONS; CANCER INCIDENCE; HEAD C1 [Deschler, Daniel G.; Rocco, James W.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Deschler, Daniel G.; Rocco, James W.] Massachusetts Eye & Ear Infirm, Div Head & Neck Surg, Boston, MA 02114 USA. [Rocco, James W.] Massachusetts Eye & Ear Infirm, Head & Neck Mol Oncol Res Lab, Boston, MA 02114 USA. [Haughey, Bruce H.] Washington Univ, Sch Med, Head & Neck Canc Ctr, St Louis, MO USA. RP Deschler, DG (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM daniel_deschler@meei.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND BN 978-3-8055-9972-6 PY 2012 BP 68 EP 69 DI 10.1159/000338195 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA BCO08 UT WOS:000310813700035 ER PT B AU Zeitels, SM Guerra, GL AF Zeitels, Steven M. Guerra, Gerardo Lopez BE Cernea, CR TI Practical Suggestions for Phonomicrosurgical Treatment of Benign Vocal Fold Lesions SO PEARLS AND PITFALLS IN HEAD AND NECK SURGERY: PRACTICAL TIPS TO MINIMIZE COMPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID LASER TREATMENT; MANAGEMENT; SINGERS C1 [Zeitels, Steven M.; Guerra, Gerardo Lopez] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Zeitels, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. EM zeitels.steven@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND BN 978-3-8055-9972-6 PY 2012 BP 72 EP 73 DI 10.1159/000337966 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA BCO08 UT WOS:000310813700037 ER PT J AU Ma, D Zhang, B Hoffmann, U Sundrup, MG Eikermann, M Isaacs, L AF Ma, Da Zhang, Ben Hoffmann, Ulrike Sundrup, Martina Grosse Eikermann, Matthias Isaacs, Lyle TI Acyclic Cucurbit[n]uril-Type Molecular Containers Bind Neuromuscular Blocking Agents In Vitro and Reverse Neuromuscular Block In Vivo SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE cucurbit[n]uril; host-guest systems; medicinal chemistry; molecular recognition; neuromuscular blocking agents ID HOST-GUEST COMPLEXATION; ACETYLCHOLINE-RECEPTOR; MUSCLE-ACTIVITY; DRUG-DELIVERY; CUCURBITURIL; SUGAMMADEX; CHEMISTRY; NANOPARTICLES; RECOGNITION; ANESTHETICS C1 [Ma, Da; Zhang, Ben; Isaacs, Lyle] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Hoffmann, Ulrike; Sundrup, Martina Grosse; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Hoffmann, Ulrike; Sundrup, Martina Grosse; Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Hoffmann, Ulrike] Tech Univ Munich, Klin Anaesthesiol, Klinikum Rechts Isar, D-81675 Munich, Germany. [Eikermann, Matthias] Essen Duisburg Univ, Dept Anesthesia & Intens Care Med, Duisburg, Germany. RP Eikermann, M (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM meikermann@partners.org; LIsaacs@umd.edu RI Isaacs, Lyle/B-4472-2009; Zhang, Ben/F-6580-2014 OI Isaacs, Lyle/0000-0002-4079-332X; FU National Science Foundation [CHE-0615049, CHE-1110911]; Department of Anesthesia, Critical Care, and Pain Medicine at the Massachusetts General Hospital in Boston FX We thank the National Science Foundation (CHE-0615049 and CHE-1110911 to L.I.) for financial support. M. E. thanks the Department of Anesthesia, Critical Care, and Pain Medicine at the Massachusetts General Hospital in Boston for financial support. NR 49 TC 44 Z9 44 U1 3 U2 72 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 45 BP 11358 EP 11362 DI 10.1002/anie.201206031 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 034LJ UT WOS:000310874400034 PM 23047893 ER PT J AU Tegos, G Mylonakis, E AF Tegos, George Mylonakis, Eleftherios BE Tegos, G Mylonakis, E TI Advances in Molecular and Cellular Microbiology 22 Antimicrobial Drug Discovery Emerging Strategies Introduction SO ANTIMICROBIAL DRUG DISCOVERY: EMERGING STRATEGIES SE Advances in Molecular and Cellular Microbiology LA English DT Editorial Material; Book Chapter ID RESISTANT STAPHYLOCOCCUS-AUREUS; PHOTODYNAMIC INACTIVATION; PATHOGENIC BACTERIA; ANTIBIOTIC-ACTIVITY; EFFLUX PUMPS; MODEL HOST; PHOTOINACTIVATION; TUBERCULOSIS; METABOLITES; INHIBITORS C1 [Tegos, George] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Tegos, George] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Tegos, George] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Mylonakis, Eleftherios] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Tegos, G (reprint author), Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. EM gtegos@partners.org; emylonakis@partners.org NR 36 TC 3 Z9 3 U1 0 U2 0 PU CABI PUBLISHING-C A B INT PI WALLINGFORD PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND BN 978-1-84593-943-4 J9 ADV M C M PY 2012 IS 22 BP 1 EP 6 D2 10.1079/9781845939434.0000 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCU57 UT WOS:000311503500001 ER PT J AU Coleman, JJ Mylonakis, E AF Coleman, Jeffrey J. Mylonakis, Eleftherios BE Tegos, G Mylonakis, E TI In Vivo High-throughput Antimicrobial Discovery Screens Utilizing Caenorhabditis elegans as an Alternative Host SO ANTIMICROBIAL DRUG DISCOVERY: EMERGING STRATEGIES SE Advances in Molecular and Cellular Microbiology LA English DT Article; Book Chapter ID ANIMAL INFECTION MODEL; INNATE IMMUNE-RESPONSE; CANDIDA-ALBICANS; ANTIFUNGAL COMPOUNDS; DRUG DISCOVERY; VIRULENCE; IDENTIFICATION; PATHOGENESIS; ENTEROCOCCI; RESISTANCE C1 [Coleman, Jeffrey J.; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Coleman, JJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jjcoleman@partners.org; emylonakis@partners.org OI Coleman, Jeffrey/0000-0001-8579-1996 NR 42 TC 0 Z9 0 U1 0 U2 2 PU CABI PUBLISHING-C A B INT PI WALLINGFORD PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND BN 978-1-84593-943-4 J9 ADV M C M PY 2012 IS 22 BP 292 EP 299 D2 10.1079/9781845939434.0000 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCU57 UT WOS:000311503500019 ER PT J AU Sharma, SK Dai, TH Hamblin, MR AF Sharma, Sulbha K. Dai, Tianhong Hamblin, Michael R. BE Tegos, G Mylonakis, E TI Antimicrobial Photosensitizers: Harnessing the Power of Light to Treat Infections SO ANTIMICROBIAL DRUG DISCOVERY: EMERGING STRATEGIES SE Advances in Molecular and Cellular Microbiology LA English DT Article; Book Chapter ID RESISTANT STAPHYLOCOCCUS-AUREUS; GRAM-POSITIVE BACTERIA; MESOSUBSTITUTED CATIONIC PORPHYRINS; CONVENTIONAL ENDODONTIC TREATMENT; TARGETED PHOTODYNAMIC THERAPY; 5-AMINOLEVULINIC ACID; IN-VITRO; HELICOBACTER-PYLORI; METHYLENE-BLUE; EFFICIENT PHOTOSENSITIZERS C1 [Sharma, Sulbha K.; Dai, Tianhong; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Sharma, SK (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM ssharma0@partners.org; tdai@partners.org; hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 NR 84 TC 4 Z9 4 U1 0 U2 1 PU CABI PUBLISHING-C A B INT PI WALLINGFORD PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND BN 978-1-84593-943-4 J9 ADV M C M PY 2012 IS 22 BP 310 EP 322 D2 10.1079/9781845939434.0000 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCU57 UT WOS:000311503500021 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Thomas Bewick: The complete illustrative work SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PY 2012 VL 10 IS 4 BP 443 EP 445 DI 10.1080/17460654.2012.723503 PG 4 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 034DC UT WOS:000310849300007 ER PT J AU Jensen, JK Ueland, T Aukrust, P Antonsen, L Kristensen, SR Januzzi, JL Ravkilde, J AF Jensen, J. K. Ueland, T. Aukrust, P. Antonsen, L. Kristensen, S. R. Januzzi, J. L. Ravkilde, J. TI Highly Sensitive Troponin T in Patients with Acute Ischemic Stroke SO EUROPEAN NEUROLOGY LA English DT Article DE Highly sensitive troponin; Acute ischemic stroke; Long-term prognosis ID CORONARY-ARTERY-DISEASE; CARDIAC TROPONIN; MYOCARDIAL-INFARCTION; HEART-FAILURE; ELEVATED TROPONIN; PROGNOSTIC VALUE; EARLY-DIAGNOSIS; ASSAY; MORTALITY; ASSOCIATION AB Background: Newly developed troponin assays have superior diagnostic and prognostic performance in acute coronary syndrome (ACS), when compared to conventional troponin assays; however, highly sensitive troponin has not been evaluated in patients with acute ischemic stroke. Methods: Highly sensitive troponin T (hsTnT) was measured daily during the first 4 days in 193 consecutive patients with acute ischemic stroke without overt ACS or atrial fibrillation. The patients were previously tested normal with a fourth-generation TnT assay. The patients were followed for 47 months, with all-cause and cardiovascular mortality end-points. Results: A total of 33.7% of the patients had hsTnT levels 1 14 ng/l following admission. Patients with increased hsTnT were older, had decreased hemoglobin levels and increased creatinine, NT-proBNP and CRP levels. hsTnT concentrations at admission were significantly higher in decedents than in survivors. After adjustment for stroke severity, C-reactive protein, age, NT-proBNP and prior heart and/or renal failure, hsTnT levels were not a significant predictor of long-term allcause or cardiovascular mortality. Conclusion: Elevated levels of hsTnT are frequently present in patients with acute ischemic stroke previously tested normal with a fourth-generation TnT assay. hsTnT did not provide additional prognostic information in these subjects. Copyright (C) 2012 S. Karger AG, Basel C1 [Jensen, J. K.; Antonsen, L.] Odense Univ Hosp, Dept Cardiol, DK-5000 Odense C, Denmark. [Ueland, T.; Aukrust, P.] Univ Oslo, Internal Med Res Inst, Oslo, Norway. [Aukrust, P.] Univ Oslo, Rikshosp, Sect Clin Immunol & Infect Dis, Oslo Univ Hosp, N-0027 Oslo, Norway. [Ueland, T.; Aukrust, P.] Univ Oslo, Fac Med, Oslo, Norway. [Kristensen, S. R.; Ravkilde, J.] Aarhus Univ Hosp, Heart Ctr Aalborg, Dept Cardiol, Aalborg, Denmark. [Kristensen, S. R.; Ravkilde, J.] Aarhus Univ Hosp, Heart Ctr Aalborg, Cardiovasc Res Ctr, Aalborg, Denmark. [Januzzi, J. L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Jensen, JK (reprint author), Odense Univ Hosp, Dept Cardiol, Sdr Blvd 29, DK-5000 Odense C, Denmark. EM jesperkjensen@dadlnet.dk RI Kristensen, Soren/D-4440-2013 OI Kristensen, Soren/0000-0002-2649-506X NR 31 TC 9 Z9 9 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PY 2012 VL 68 IS 5 BP 287 EP 293 DI 10.1159/000341340 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 036PZ UT WOS:000311042800005 PM 23051820 ER PT J AU Pang, CY Jiang, G Wang, SP Hu, BQ Liu, QZ Deng, YP Huang, XD AF Pang, Chaoyang Jiang, Gang Wang, Shipeng Hu, Benqiong Liu, Qingzhong Deng, Youping Huang, Xudong TI Gene order computation using Alzheimer's DNA microarray gene expression data and the Ant Colony Optimisation algorithm SO INTERNATIONAL JOURNAL OF DATA MINING AND BIOINFORMATICS LA English DT Article DE gene order; ACO; ant colony optimisation; AD; Alzheimer's disease; DNA microarray ID SELF-ORGANIZING MAPS; CLUSTER-ANALYSIS; DISEASE; PATTERNS; NETWORK; STRESS AB As Alzheimer's Disease (AD) is the most common form of dementia, the study of AD-related genes via biocomputation is an important research topic. One method of studying AD-related gene is to cluster similar genes together into a gene order. Gene order is a good clustering method as the results can be optimal globally while other clustering methods are only optimal locally. Herein we use the Ant Colony Optimisation (ACO)-based algorithm to calculate the gene order from an Alzheimer's DNA microarray dataset. We test it with four distance measurements: Pearson distance, Spearmen distance, Euclidean distance, and squared Euclidean distance. Our computing results indicate: a different distance formula generated a different quality of gene order the squared Euclidean distance approach produced the optimal AD-related gene order. C1 [Huang, Xudong] Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Boston, MA 02114 USA. [Huang, Xudong] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Pang, Chaoyang; Jiang, Gang; Wang, Shipeng] Sichuan Normal Univ, Grp Gene Computat, Coll Math & Software Sci, Chengdu 610066, Peoples R China. [Hu, Benqiong] Chengdu Univ Technol, Coll Informat Management, Chengdu 610059, Peoples R China. [Liu, Qingzhong] Sam Houston State Univ, Dept Comp Sci, Huntsville, TX 77341 USA. [Deng, Youping] Rush Univ, Med Ctr, Ctr Canc, Chicago, IL 60612 USA. RP Huang, XD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Boston, MA 02114 USA. EM cypang@live.cn; jianggang060615@163.com; tylererer@126.com; bqh402@126.com; qxl005@shsu.edu; youping_deng@rush.edu; xhuang3@partners.org FU BWH Radiology Department; Education Department of Sichuan Province, China [09zz028] FX The work was supported by funds from BWH Radiology Department and key developing program of technology innovation from Education Department of Sichuan Province (No. 09zz028), China. The authors appreciate the advice from Prof. J. Zhang of Sichuan Normal University. The authors acknowledge the help from the following members of gene computation team: W. Hu, C-B. Wang, Q. Yang, X. Li, H. Liu, L.-J. Ye, J-L. Zhou, P. Shuai, Y. Li, Z-C. Dan, M-X. Chen, D-X. Zhang, L. Yang, and X-P. Xia. Finally, the authors would like to thank Ms. Kimberly Lawson of BWH Radiology Department for her manuscript editing. NR 38 TC 1 Z9 1 U1 1 U2 7 PU INDERSCIENCE ENTERPRISES LTD PI GENEVA PA WORLD TRADE CENTER BLDG, 29 ROUTE DE PRE-BOIS, CASE POSTALE 856, CH-1215 GENEVA, SWITZERLAND SN 1748-5673 J9 INT J DATA MIN BIOIN JI Int. J. Data Min. Bioinform. PY 2012 VL 6 IS 6 BP 617 EP 632 DI 10.1504/IJDMB.2012.050247 PG 16 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 037WK UT WOS:000311137000004 PM 23356011 ER PT J AU Awwad, J Ghazeeri, G Toth, T Hannoun, A Abou Abdallah, M Farra, C AF Awwad, Johnny Ghazeeri, Ghina Toth, Thomas Hannoun, Antoine Abou Abdallah, Michel Farra, Chantal TI Fever in women may interfere with follicular development during controlled ovarian stimulation SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE hyperthermia; febrile illness; oocytes; controlled ovarian stimulation; follicular development ID MATERNAL HEAT-STRESS; LACTATING HOLSTEIN COWS; DOMINANT FOLLICLES; MEIOTIC MATURATION; DAIRY-CATTLE; EMBRYOS; OOCYTE; GROWTH; STEROIDOGENESIS; HYPERTHERMIA AB Purpose: This study aims to evaluate the effects of fever on follicular development in women undergoing controlled ovarian stimulation during in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) cycles. Materials and methods: This was a retrospective observational self-controlled study at a tertiary-care fertility centre. Six gonadotropin stimulation cycles characterised by poor ovarian response in which women reported the occurrence of a febrile illness, were considered for evaluation. Fever-exposed cycles were compared to the next stimulation cycle in the same women. Primary outcome measures were final number of pre-ovulatory follicles (>= 16mm) and final peak serum estradiol levels (pg/mL). Other outcome measures were final number of medium-sized follicles (12-15 mm), final mean estradiol serum level per follicle >= 12mm (pg/mL), total days of stimulation and total gonadotropin ampoules utilised. Results: Fever-exposed cycles were associated with significantly lower number of pre-ovulatory follicles (0.7 +/- 0.8), significantly higher number of medium-size follicles (21.0 +/- 4.5), and significantly reduced serum estradiol per follicle >= 12mm (50.7 +/- 11.7 pg/mL). They also required a significantly longer duration of ovarian stimulation (15.7 +/- 3.3 days) and a significantly increased number of gonadotropin ampoules (47.2 +/- 10.9). Four women had polycystic ovary syndrome and one hypothalamic hypogonadism. Conclusion: This preliminary report suggests a possible negative effect of fever on follicular development and ovarian estradiol production in some women undergoing controlled ovarian stimulation. C1 [Farra, Chantal] Amer Univ Beirut, Dept Pathol & Lab Med, Med Ctr, Beirut, Lebanon. [Awwad, Johnny; Ghazeeri, Ghina; Hannoun, Antoine; Abou Abdallah, Michel] Amer Univ Beirut, Dept Obstet & Gynecol, Med Ctr, Beirut, Lebanon. [Toth, Thomas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA USA. RP Farra, C (reprint author), Amer Univ Beirut, Dept Pathol & Lab Med, Med Ctr, POB 113-6044, Beirut, Lebanon. EM cf07@aub.edu.lb NR 28 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PY 2012 VL 28 IS 8 BP 742 EP 746 DI 10.3109/02656736.2012.724516 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 039HU UT WOS:000311236300006 PM 23072616 ER PT J AU Goulidaki, N Palumbo, T Vorvis, C Spandidos, DA Sourvinos, G Iliopoulos, D AF Goulidaki, Nektaria Palumbo, Tiziana Vorvis, Christina Spandidos, Demetrios A. Sourvinos, George Iliopoulos, Dimitrios TI Identification of host miRNAs that are implicated in the NF kappa B and PI3K pathways during HCMV lytic infection SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Goulidaki, Nektaria; Spandidos, Demetrios A.; Sourvinos, George] Univ Crete, Fac Med, Dept Virol, Iraklion, Crete, Greece. [Palumbo, Tiziana; Vorvis, Christina; Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PY 2012 VL 30 SU 1 MA 329 BP S62 EP S62 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031ON UT WOS:000310651600230 ER PT J AU Goulidaki, N Palumbo, T Vorvis, C Spandidos, DA Sourvinos, G Iliopoulos, D AF Goulidaki, Nektaria Palumbo, Tiziana Vorvis, Christina Spandidos, Demetrios A. Sourvinos, George Iliopoulos, Dimitrios TI HCMV controls the expression of miR-155 and miR-548c through NF kappa B activation SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Goulidaki, Nektaria; Spandidos, Demetrios A.; Sourvinos, George] Univ Crete, Fac Med, Dept Virol, Iraklion, Crete, Greece. [Palumbo, Tiziana; Vorvis, Christina; Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PY 2012 VL 30 SU 1 MA 330 BP S62 EP S62 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031ON UT WOS:000310651600231 ER PT J AU Goulidaki, N Palumbo, T Vorvis, C Spandidos, DA Sourvinos, G Iliopoulos, D AF Goulidaki, Nektaria Palumbo, Tiziana Vorvis, Christina Spandidos, Demetrios A. Sourvinos, George Iliopoulos, Dimitrios TI Gene targets of cellular miRNAs differentially expressed during HCMV lytic infection SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Goulidaki, Nektaria; Spandidos, Demetrios A.; Sourvinos, George] Univ Crete, Fac Med, Dept Virol, Iraklion, Crete, Greece. [Palumbo, Tiziana; Vorvis, Christina; Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PY 2012 VL 30 SU 1 MA 328 BP S61 EP S61 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031ON UT WOS:000310651600229 ER PT J AU Goulidaki, N Palumbo, T Vorvis, C Spandidos, DA Sourvinos, G Iliopoulos, D AF Goulidaki, Nektaria Palumbo, Tiziana Vorvis, Christina Spandidos, Demetrios A. Sourvinos, George Iliopoulos, Dimitrios TI Human Cytomegalovirus dynamically induces a host miRNA response favoring viral lytic infection SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Goulidaki, Nektaria; Spandidos, Demetrios A.; Sourvinos, George] Univ Crete, Fac Med, Dept Virol, Iraklion, Crete, Greece. [Palumbo, Tiziana; Vorvis, Christina; Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PY 2012 VL 30 SU 1 MA 327 BP S61 EP S61 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031ON UT WOS:000310651600228 ER PT J AU Kobayashi, KS AF Kobayashi, Koichi S. TI Molecular mechanism of downregualtion of MHC class I molecules in cancer SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Meeting Abstract C1 [Kobayashi, Koichi S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PY 2012 VL 30 SU 1 MA 103 BP S5 EP S5 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031ON UT WOS:000310651600004 ER PT J AU Ghoshhajra, BB Maurovich-Horvat, P Techasith, T Medina, HM Verdini, D Sidhu, MS Blankstein, R Brady, TJ Cury, RC AF Ghoshhajra, Brian B. Maurovich-Horvat, Pal Techasith, Tust Medina, Hector M. Verdini, Daniel Sidhu, Manavjot S. Blankstein, Ron Brady, Thomas J. Cury, Ricardo C. TI Infarct detection with a comprehensive cardiac CT protocol SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Diagnostic imaging; Cardiovascular disease; Myocardial perfusion; Myocardial infarction; X-ray computed tomography; Myocardial perfusion imaging; Cardiac-gated imaging techniques ID CORONARY-ARTERY-DISEASE; MULTIDETECTOR COMPUTED-TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; AMERICAN-HEART-ASSOCIATION; LEFT-VENTRICULAR FUNCTION; DUAL-SOURCE CT; MAGNETIC-RESONANCE; DIAGNOSTIC PERFORMANCE; STRESS PERFUSION; ADIPOSE-TISSUE AB BACKGROUND: Cardiac CT has the potential to offer comprehensive infarct detection by assessing regional wall motion abnormalities (RWMAs), rest perfusion defects (RPDs), and delayed contrast enhancement (DCE). However, the diagnostic accuracy of these techniques for the detection of myocardial infarction (MI) is unknown. METHODS: Forty-eight patients with intermediate-to-high probability for coronary artery disease after single-photon emitting CT myocardial perfusion imaging were prospectively enrolled for a research comprehensive 64-detector row dual-source cardiac CT protocol that included cine images for RWMA, first-pass images for RPD, and delayed images for DCE. Blinded readers independently assessed each technique. Subsequently, a final combined analysis (cine + rest + DCE) was performed. The universal definition for MI by the 2007 American Heart Association task force was used as the "gold standard." RESULTS: Twenty-four of 48 patients (50%) had infarct by the universal definition. The combined CT analysis was most accurate (90%) with the highest per-patient sensitivity (88%) and specificity (92%) versus individual assessments (RWMA, 79% and 88%; RPD, 67% and 92%; DCE, 79% and 88%). Similar findings were observed on a per-vessel basis analysis. A combination of DCE and eine showed a good accuracy (85%) and high sensitivity (92%). CONCLUSIONS: Infarct detection with CT is feasible with overall good diagnostic accuracy compared with the universal definition. A combined evaluation that included all techniques (eine, RPD, and DCE) had the highest diagnostic accuracy. These findings may have implications when designing future clinical and research CT protocols for optimal infarct detection. (C) 2012 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Ghoshhajra, Brian B.; Maurovich-Horvat, Pal; Techasith, Tust; Medina, Hector M.; Verdini, Daniel; Sidhu, Manavjot S.; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Ghoshhajra, Brian B.; Maurovich-Horvat, Pal; Techasith, Tust; Medina, Hector M.; Verdini, Daniel; Sidhu, Manavjot S.; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Ghoshhajra, Brian B.; Maurovich-Horvat, Pal; Techasith, Tust; Medina, Hector M.; Verdini, Daniel; Sidhu, Manavjot S.; Brady, Thomas J.; Cury, Ricardo C.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Blankstein, Ron] Brigham & Womens Hosp, Div Cardiovasc, Noninvas Cardiovasc Imaging Program, Boston, MA 02115 USA. [Cury, Ricardo C.] Baptist Cardiac & Vasc Inst, Cardiovasc MRI & CT Program, Miami, FL USA. [Blankstein, Ron] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Sidhu, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM msidhu1@partners.org OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU Astellas Pharma, Inc; National Institutes of Health [1T32 HL076136]; RSNA [213740]; Astellas, Pharma, Inc FX This study was supported in part by a grant from Astellas Pharma, Inc, the National Institutes of Health (grant 1T32 HL076136 to Drs. Blankstein and Ghoshhajra), from RSNA 213740 (Dr. Ghoshhajra), and Astellas, Pharma, Inc (Dr. Cury). NR 35 TC 8 Z9 11 U1 0 U2 1 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 JAN-FEB PY 2012 VL 6 IS 1 BP 14 EP 23 DI 10.1016/j.jcct.2011.10.014 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 035HK UT WOS:000310933800003 PM 22210535 ER PT J AU Uthamalingam, S Gurm, GS Sidhu, MS Verdini, DJ Vorasettakarnkij, Y Engel, LC Blankstein, R Mamuya, WS Hoffman, U Brady, TJ Cury, RC Ghoshhajra, BB AF Uthamalingam, Shanmugam Gurm, Gagandeep S. Sidhu, Manavjot S. Verdini, Daniel J. Vorasettakarnkij, Yongkasem Engel, Leif-Christopher Blankstein, Ron Mamuya, Wilfred S. Hoffman, Udo Brady, Thomas J. Cury, Ricardo C. Ghoshhajra, Brian B. TI Comparison of dual-source 64-slice adenosine stress CT perfusion with stress-gated SPECT-MPI for evaluation of left ventricular function and volumes SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Stress myocardial CT perfusion; Single-photon emission CT myocardial perfusion imaging, SPECT-MPI; Stress testing; Coronary artery disease ID CARDIAC COMPUTED-TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; AMERICAN-HEART-ASSOCIATION; EJECTION FRACTIONS; NUCLEAR CARDIOLOGY; ANGIOGRAPHY; SURVIVAL; ECHOCARDIOGRAPHY; ISCHEMIA; DEFECTS AB BACKGROUND: Evaluation of left ventricular (LV) volumes and ejection fraction (LVEF) represent important components of pharmacologic stress imaging with either myocardial CT perfusion (CTP) or gated single-photon emission CT (SPECT) myocardial perfusion imaging (SPECT-MPI). OBJECTIVES: We compared measurements of left ventricular function and volumes obtained with CTP and SPECT-MPI. METHODS: Forty-seven patients (mean age, 62 +/- 11 years; male, n = 39) underwent stress CTP and SPECT-MPI. LVEF (in %), end-systolic volume (ESV; in mL), and end-diastolic volume (EDV; in mL) derived from stress CTP images were compared with SPECT-MP1. RESULTS: Stress CTP was in good agreement with SPECT-MPI for quantification of LVEF (r = 0.91), EDV (r = 0.75), and ESV (r = 0.83; all P < 0.001). The mean LVEF measured by stress CTP (66% +/- 17%) was similar to SPECT-MPI (64% +/- 15%). Similar values were also derived for mean EDV (123 +/- 30 mL vs 120 +/- 34 mL) and ESV (44 +/- 28 mL vs 51 +/- 34 mL) for CTP and SPECT-MPI, respectively. Good agreement was also shown between both techniques for the assessment of regional wall motion with identical wall motion scores in 95.3% of the segments (kappa = 0.79). CONCLUSIONS: LVEF and LV volume parameters as determined by dual-source 64-slice adenosine stress CTP show a high correlation with values obtained with stress-gated SPECT-MPI. (C) 2012 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Uthamalingam, Shanmugam; Gurm, Gagandeep S.; Sidhu, Manavjot S.; Verdini, Daniel J.; Vorasettakarnkij, Yongkasem; Engel, Leif-Christopher; Mamuya, Wilfred S.; Hoffman, Udo; Brady, Thomas J.; Ghoshhajra, Brian B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MRI PET CT Program,Dept Radiol, Boston, MA 02114 USA. [Vorasettakarnkij, Yongkasem] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Blankstein, Ron] Harvard Univ, Sch Med, Div Cardiovasc, Brigham & Womens Hosp, Boston, MA 02114 USA. [Cury, Ricardo C.] Baptist Hosp Miami, Baptist Cardiac & Vasc Inst, Cardiovasc MRI & CT Program, Miami, FL USA. [Blankstein, Ron] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02114 USA. RP Ghoshhajra, BB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MRI PET CT Program,Dept Radiol, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM bghoshhajra@partners.org NR 24 TC 2 Z9 2 U1 1 U2 2 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 JAN-FEB PY 2012 VL 6 IS 1 BP 24 EP 30 DI 10.1016/j.jcct.2011.10.016 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 035HK UT WOS:000310933800004 PM 22222164 ER PT J AU Kilcullen, NM Woo, JKH Abbara, S Barrett, CD Baggish, A AF Kilcullen, Niamh M. Woo, James K. H. Abbara, Suhny Barrett, Conor D. Baggish, Aaron TI The missing left atrial appendage SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Echocardiography; CT; Left atrial appendage; Multimodality imaging; Anatomical variation; Congenital heart disease AB A 34 year old man underwent a transesophageal echocardiogram (TEE) prior to implantation of a biventricular ICD and DC cardioversion, to exclude left atrium and left atrial appendage thrombus. He had a history of repaired tetralogy of Fallot as a child, Stickler syndrome, atrial flutter and was status post recent mitral valve replacement, pulmonary valve replacement and tricuspid valve repair. The left atrial appendage was not visualized on TEE. A cardiac CT clarified that there was a left atrial appendage and provided an explanation as to why it was not visualized on TEE, highlighting the importance of multimodality imaging in patients with complex congenital heart disease. (C) 2012 Society of Cardiovascular Computed Tomography. All rights reserved. C1 [Kilcullen, Niamh M.; Barrett, Conor D.; Baggish, Aaron] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Woo, James K. H.; Abbara, Suhny] Massachusetts Gen Hosp, Dept Radiol, Cardiac Imaging Div, Boston, MA 02114 USA. RP Kilcullen, NM (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. EM niamhkilcullen@doctors.org.uk NR 2 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 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD JAN-FEB PY 2012 VL 6 IS 1 BP 60 EP 61 DI 10.1016/j.jcct.2011.07.002 PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 035HK UT WOS:000310933800009 PM 22212436 ER PT J AU Lehavot, K Ben-Zeev, D Neville, RE AF Lehavot, Keren Ben-Zeev, Dror Neville, Robin E. TI Ethical Considerations and Social Media: A Case of Suicidal Postings on Facebook SO JOURNAL OF DUAL DIAGNOSIS LA English DT Article DE social media; Facebook; serious mental illness; suicide; ethics ID INFORMATION; SCHIZOPHRENIA; PSYCHOTHERAPY; DEPRESSION; MANAGEMENT; NETWORKING; STUDENTS; INTERNET; MYSPACE; SITE AB Social media sites such as Facebook are increasingly accessed and used by mental health professionals and clients alike, creating fertile ground for ethical challenges and complex decision making. We review a case report in which a clinician discovers suicidal ideation on Facebook (in the form of both photos and explicit statements) by a client with serious mental illness. Ethical issues relevant to this case and others involving social media are discussed, including the principles of beneficence and maleficence, issues of privacy and confidentiality, multiple relationships, clinical judgment, and informed consent. In using social media to obtain information about clients, we highlight potential benefits and harm, including harm to the therapeutic alliance, the difference and consequent impact of actual versus perceived privacy violations, and the necessity of obtaining the client's informed consent. (Journal of Dual Diagnosis, 8:341-346, 2012) C1 [Lehavot, Keren] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. [Lehavot, Keren] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Ben-Zeev, Dror] Dartmouth Psychiat Res Ctr, Geisel Sch Med Dartmouth, Lebanon, NH USA. [Ben-Zeev, Dror] Thresholds Dartmouth Res Ctr, Chicago, IL USA. [Neville, Robin E.] Thresholds Psychiat Rehabil Ctr, Chicago, IL USA. RP Lehavot, K (reprint author), 1660 S Columbian Way,116 POC, Seattle, WA 98108 USA. EM klehavot@uw.edu NR 34 TC 9 Z9 9 U1 5 U2 46 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1550-4263 J9 J DUAL DIAGN JI J. Dual Diagn. PY 2012 VL 8 IS 4 SI SI BP 341 EP 346 DI 10.1080/15504263.2012.718928 PG 6 WC Psychology, Clinical; Substance Abuse; Psychiatry SC Psychology; Substance Abuse; Psychiatry GA 035OJ UT WOS:000310956300011 ER PT J AU Oktay, JS Nedjat-Haiem, FR Davis, C Kern, KC AF Oktay, Julianne S. Nedjat-Haiem, Frances R. Davis, Cindy Kern, Kathleen C. TI Distress Screening: Experiences of Oncology Social Workers SO JOURNAL OF PSYCHOSOCIAL ONCOLOGY LA English DT Article DE cancer; oncology social work; distress screening; social workers; NCCN Distress Thermometer ID CANCER; THERMOMETER AB The purpose of this pilot study was to explore oncology social workers experiences with the introduction and use of distress screening tools with patients who are diagnosed with cancer. Focus groups were conducted with 15 oncology social workers, who were primarily employed in large hospitals or cancer centers. The results fell into three broad areas: initiating distress screening, adapting distress screening to the setting, and evaluating distress screening. Findings revealed that social workers face many decisions as they adapt distress screening to their settings, including when and how to measure distress, and how to refer patients to services. Social workers were concerned about being overwhelmed with referrals and sought to manage the screening to better identify those who are likely to benefit from services. This research suggests a need for further study, the development of practice guidelines, and training of oncology social workers. C1 [Oktay, Julianne S.] Univ Maryland, Sch Social Work, Baltimore, MD 21201 USA. [Nedjat-Haiem, Frances R.] HSR&D Ctr Excellence, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Davis, Cindy] Univ Tennessee, Coll Social Work, Nashville, TN USA. [Kern, Kathleen C.] Clifton T Perkins Hosp Ctr, Jessup, MD USA. RP Oktay, JS (reprint author), Univ Maryland, Sch Social Work, 525 W Redwood St, Baltimore, MD 21201 USA. EM joktay@ssw.umaryland.edu NR 17 TC 4 Z9 4 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0734-7332 J9 J PSYCHOSOC ONCOL JI J. Psychosoc. Oncol. PY 2012 VL 30 IS 6 SI SI BP 652 EP 666 DI 10.1080/07347332.2012.721490 PG 15 WC Psychology, Social SC Psychology GA 030TT UT WOS:000310593700004 PM 23101549 ER PT J AU Song, JW Daubriac, J Tse, JM Bazou, D Munn, LL AF Song, Jonathan W. Daubriac, Julien Tse, Janet M. Bazou, Despina Munn, Lance L. TI RhoA mediates flow-induced endothelial sprouting in a 3-D tissue analogue of angiogenesis SO LAB ON A CHIP LA English DT Article ID SHEAR-STRESS; CELL-CULTURE; CAPILLARY MORPHOGENESIS; INTERSTITIAL FLOW; SMALL GTPASES; IN-VITRO; MIGRATION; MATRIX; GENERATION; FILOPODIA AB Endothelial cells (ECs) integrate signals from the local microenvironment to guide their behaviour. RhoA is involved in vascular endothelial growth factor (VEGF)-driven angiogenesis, but its role in mechanotransduction during sprouting has not been established. Using dominant negative cell transfections in a microfluidic device that recapitulates angiogenic sprouting, we show that endothelial cells respond to interstitial flow in a RhoA-dependent manner while invading a 3-D extracellular matrix. Furthermore, RhoA regulates flow-induced, but not VEGF gradient-induced, tip cell filopodial extensions. Thus, RhoA pathways mediate mechanically-activated but not VEGF-induced endothelial morphogenesis. C1 [Munn, Lance L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumour Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumour Biol, Charlestown, MA 02129 USA. EM munn@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; Song, Jonathan/C-1922-2013 OI Munn, Lance/0000-0003-0698-7232; Song, Jonathan/0000-0002-6991-5298 FU National Institutes of Health [R01CA149285, T32CA073479] FX This study was supported by grants from the National Institutes of Health: R01CA149285 (LLM) and T32CA073479. NR 42 TC 9 Z9 9 U1 2 U2 21 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2012 VL 12 IS 23 BP 5000 EP 5006 DI 10.1039/c2lc40389g PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 035BJ UT WOS:000310916500010 PM 23073300 ER PT J AU Athanasoulia, AP Ising, M Pfister, H Mantzoros, CS Stalla, GK Sievers, C AF Athanasoulia, A. P. Ising, M. Pfister, H. Mantzoros, C. S. Stalla, G. K. Sievers, C. TI Distinct Dopaminergic Personality Patterns in Patients with Prolactinomas: A Comparison with Nonfunctioning Pituitary Adenoma Patients and Age- and Gender-Matched Controls SO NEUROENDOCRINOLOGY LA English DT Article DE Prolactinoma; Personality; Dopamine; Pituitary; Nonfunctioning pituitary adenomas ID QUALITY-OF-LIFE; LONG-TERM CURE; CUSHINGS-SYNDROME; NOVELTY SEEKING; HARM AVOIDANCE; DISEASE; TRAITS; HYPERPROLACTINEMIA; PSYCHOPATHOLOGY; POLYMORPHISMS AB Introduction: Personality patterns such as extraversion and novelty seeking have been associated with an altered dopaminergic activity in healthy subjects. Patients with prolactinomas have been described as exhibiting an altered dopaminergic tone and are often treated with dopamine agonists. Little is known about the personality traits of this patient group. Hence, we aimed at examining whether patients with prolactinomas exhibit modified personality patterns compared to patients with nonfunctioning pituitary adenomas and healthy controls. Subjects/Methods: In this cross-sectional study, 86 patients with prolactinomas and 58 patients with nonfunctioning pituitary adenomas (NFPA) were compared with 172 mentally healthy age- and gender-matched controls. To assess personality traits, standardized personality questionnaires (Eysenck personality questionnaire-EPQ-RK and Tridimensional Personality Questionnaire devised by Cloninger-TPQ) were administered. Results: Patients with either prolactinomas or NFPA showed a distinct personality profile compared to the normal population, characterized by increased neuroticism and they also answered in a socially desirable mode. On harm-avoidant total and subscales, they presented with a higher fear of uncertainty and also increased fatigability and asthenia. The prolactinoma patients, when contrasted with the 'clinical' control group of patients with NFPA and after post hoc tests for multiple comparisons following the Bonferroni-Holm procedure showed significantly reduced extraversion (p = 0.044) and increased shyness with strangers (p = 0.044), tending to be more neurotic and present lower scores in the novelty seeking subscale impulsiveness. Conclusion: This is, to our knowledge, the first study providing new evidence of an altered personality profile of prolactinoma patients which might affect the patient-doctor relationship, treatment and patient's quality of life. Copyright (c) 2012 S. Karger AG, Basel C1 [Athanasoulia, A. P.; Stalla, G. K.; Sievers, C.] Max Planck Inst Psychiat, Dept Internal Med Endocrinol & Clin Chem, DE-80804 Munich, Germany. [Ising, M.; Pfister, H.] Max Planck Inst Psychiat, Dept Mol Psychol, DE-80804 Munich, Germany. [Mantzoros, C. S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Sch Med, Boston, MA 02215 USA. [Mantzoros, C. S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. RP Athanasoulia, AP (reprint author), Max Planck Inst Psychiat, Dept Internal Med Endocrinol & Clin Chem, Kraepelinstr 2-10, DE-80804 Munich, Germany. EM athanasoulia@mpipsykl.mpg.de FU Pfizer Pharma GmbH, Karlsruhe, Germany FX This work was supported by a scholarship from Pfizer Pharma GmbH, Karlsruhe, Germany (to A.P.-A.). NR 39 TC 7 Z9 7 U1 2 U2 13 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2012 VL 96 IS 3 BP 204 EP 211 DI 10.1159/000335996 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 039WR UT WOS:000311279000004 PM 22343218 ER PT J AU Bikle, DD AF Bikle, Daniel D. TI Protective actions of vitamin D in UVB induced skin cancer SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Review ID SQUAMOUS-CELL CARCINOMA; HUMAN EPIDERMAL-KERATINOCYTES; TRANSCRIPTION-COUPLED REPAIR; CALCIUM-SENSING RECEPTOR; BASAL-CELL; BETA-CATENIN; DNA-REPAIR; 1,25-DIHYDROXYVITAMIN D-3; ULTRAVIOLET-RADIATION; EXCISION-REPAIR AB Non-melanoma skin cancers (NMSC) are the most common type of cancer, occurring at a rate of over 1 million per year in the United States. Although their metastatic potential is generally low, they can and do metastasize, especially in the immune compromised host, and their surgical treatment is often quite disfiguring. Ultraviolet radiation (UVR) as occurs with sunlight exposure is generally regarded as causal for these malignancies, but UVR is also required for vitamin D synthesis in the skin. Based on our own data and that reported in the literature, we hypothesize that the vitamin D produced in the skin serves to suppress UVR epidermal tumor formation. In this review we will first discuss the evidence supporting the conclusion that the vitamin D receptor (VDR), with or without its ligand 1,25-dihydroxyvitamin D, limits the propensity for cancer formation following UVR. We will then explore three potential mechanisms for this protection: inhibition of proliferation and stimulation of differentiation, immune regulation, and stimulation of DNA damage repair (DDR). C1 [Bikle, Daniel D.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94112 USA. [Bikle, Daniel D.] San Francisco VA Med Ctr, Dept Dermatol, San Francisco, CA USA. [Bikle, Daniel D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Bikle, DD (reprint author), San Francisco VA Med Ctr, Dept Med, San Francisco, CA 94112 USA. EM daniel.bikle@ucsf.edu FU American Institute for Cancer Research; VA Merit Review; Department of Defense [CA110338]; National Institute of Health [RO1 AR050023] FX This work was supported by grants from the American Institute for Cancer Research, the VA Merit Review, the Department of Defense (CA110338), and the National Institute of Health (RO1 AR050023). Much of the data referred to was generated in collaboration with Drs. Arnaud Teichert, Yuko Oda, Dennis Oh, and JoEllen Welsh. Teresa Tong and Victoria Lee provided administrative support. NR 132 TC 19 Z9 20 U1 1 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X EI 1474-9092 J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2012 VL 11 IS 12 BP 1808 EP 1816 DI 10.1039/c2pp25251a PG 9 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 039XP UT WOS:000311281900005 PM 22990497 ER PT J AU Zollner, FG Emblem, KE Schad, LR AF Zoellner, Frank G. Emblem, Kyrre E. Schad, Lothar R. TI SVM-based glioma grading: Optimization by feature reduction analysis SO ZEITSCHRIFT FUR MEDIZINISCHE PHYSIK LA English DT Article DE Perfusion MRI; Glioma grading; Machine learning; Support vector machines; Computer aided diagnostics (CAD); Feature reduction ID SUPPORT VECTOR MACHINES; BLOOD-VOLUME MAPS; INDEPENDENT COMPONENT ANALYSIS; HISTOGRAM ANALYSIS; MUTUAL INFORMATION; FEATURE-SELECTION; GLIAL NEOPLASMS; BRAIN-TUMORS; MRI; CLASSIFICATION AB We investigated the predictive power of feature reduction analysis approaches in support vector machine (SVM)-based classification of glioma grade. In 101 untreated glioma patients, three analytic approaches were evaluated to derive an optimal reduction in features; (i) Pearson's correlation coefficients (PCC), (ii) principal component analysis (PCA) and (iii) independent component analysis (ICA). Tumor grading was performed using a previously reported SVM approach including whole-tumor cerebral blood volume (CB V) histograms and patient age. Best classification accuracy was found using PCA at 85% (sensitivity = 89%, specificity = 84%) when reducing the feature vector from 101 (100-bins rCBV histogram + age) to 3 principal components. In comparison, classification accuracy by PCC was 82% (89%, 77%, 2 dimensions) and 79% by ICA (87%, 75%, 9 dimensions). For improved speed (up to 30%) and simplicity, feature reduction by all three methods provided similar classification accuracy to literature values (similar to 87%) while reducing the number of features by up to 98%. C1 [Zoellner, Frank G.; Schad, Lothar R.] Heidelberg Univ, Med Fac Mannheim, D-68167 Mannheim, Germany. [Emblem, Kyrre E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Emblem, Kyrre E.] Massachusetts Gen Hosp, MGH HST AA Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Emblem, Kyrre E.] Oslo Univ Hosp, Rikshosp, Intervent Ctr, N-0027 Oslo, Norway. RP Zollner, FG (reprint author), Heidelberg Univ, Med Fac Mannheim, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. EM frank.zoellner@medma.uni-heidelberg.de RI Zollner, Frank/A-2725-2012; Emblem, Kyrre/H-6691-2012 OI Zollner, Frank/0000-0003-3405-1394; Emblem, Kyrre/0000-0002-6580-9519 NR 41 TC 9 Z9 10 U1 2 U2 8 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0939-3889 J9 Z MED PHYS JI Z. Med. Phys. PY 2012 VL 22 IS 3 BP 205 EP 214 DI 10.1016/j.zemedi.2012.03.007 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 028JY UT WOS:000310419800005 PM 22503911 ER PT J AU Gutierrez, OM Sun, CC Chen, WJ Babitt, JL Lin, HY AF Gutierrez, Orlando M. Sun, Chia Chi Chen, Wenjie Babitt, Jodie L. Lin, Herbert Y. TI Statement of Concern about a Commercial Assay Used to Measure Soluble Hemojuvelin in Humans SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Letter ID SERUM HEMOJUVELIN C1 [Gutierrez, Orlando M.] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [Sun, Chia Chi; Chen, Wenjie; Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Syst Biol, Program Anemia Signaling Res,Div Nephrol,Program, Boston, MA USA. RP Lin, HY (reprint author), Richard B Simches Res Ctr, 185 Cambridge St,CPZN 8216, Boston, MA 02114 USA. EM Lin.Herbert@mgh.harvard.edu FU NIDDK NIH HHS [R01 DK071837] NR 3 TC 9 Z9 9 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2012 VL 36 IS 4 BP 332 EP 333 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 030IH UT WOS:000310563900005 PM 23006450 ER PT J AU Stein, M Middendorp, SI Carta, V Pejo, E Raines, DE Forman, SA Sigel, E Trauner, D AF Stein, Marco Middendorp, Simon I. Carta, Valentina Pejo, Ervin Raines, Douglas E. Forman, Stuart A. Sigel, Erwin Trauner, Dirk TI Azo-Propofols: Photochromic Potentiators of GABAA Receptors SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE azo compounds; GABA receptors; ion channels; photochromism; photopharmacology ID IONOTROPIC GLUTAMATE RECEPTORS; VISUAL RESPONSES; PHARMACOLOGY; PHOTOSWITCH; CHANNELS; SUBTYPES; BINDING C1 [Middendorp, Simon I.; Carta, Valentina; Sigel, Erwin] Univ Bern, Inst Biochem & Mol Med, CH-3012 Bern, Switzerland. [Stein, Marco; Trauner, Dirk] Univ Munich, Dept Chem, D-81377 Munich, Germany. [Stein, Marco; Trauner, Dirk] Ctr Integrated Prot Sci, D-81377 Munich, Germany. [Pejo, Ervin; Raines, Douglas E.; Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Sigel, E (reprint author), Univ Bern, Inst Biochem & Mol Med, Buhlstr 28, CH-3012 Bern, Switzerland. EM erwin.sigel@ibmm.unibe.ch; dirk.trauner@Imu.de RI Sigel, Erwin/F-7736-2015 FU Fonds der Chemischen Industrie; Swiss National Science Foundation [31003A-132806/1]; European Science Foundation (ERC grant) [268795]; National Institutes of Health [GM089745, GM087316] FX We thank Dr. Peter Mayer (LMU Munich) for the determination of the X-ray structure. M. S. is grateful to the Fonds der Chemischen Industrie for a Ph.D. fellowship. This work was supported by the Swiss National Science Foundation grants 31003A-132806/1 (E.S.) and the European Science Foundation (ERC grant No 268795 to D.T.) and the National Institutes of Health (GM089745 to S.A.F and GM087316 to D.E.R.). GABA=gamma-aminobutyric acid. NR 27 TC 48 Z9 48 U1 3 U2 47 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 42 BP 10500 EP 10504 DI 10.1002/anie.201205475 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 019NC UT WOS:000309745600011 PM 22968919 ER PT J AU Krum, H Swergold, G Gammaitoni, A Peloso, PM Smugar, SS Curtis, SP Brater, DC Wang, HW Kaur, A Laine, L Weir, MR Cannon, CP AF Krum, Henry Swergold, Gary Gammaitoni, Arnold Peloso, Paul M. Smugar, Steven S. Curtis, Sean P. Brater, D. Craig Wang, Hongwei Kaur, Amarjot Laine, Loren Weir, Matthew R. Cannon, Christopher P. TI Blood Pressure and Cardiovascular Outcomes in Patients Taking Nonsteroidal Antiinflammatory Drugs SO CARDIOVASCULAR THERAPEUTICS LA English DT Article DE Cardiovascular events; Cyclo-oxygenase-2 inhibitors; Hypertension; Nonsteroidal antiinflammatory drugs ID SODIUM GASTROINTESTINAL TOLERABILITY; MYOCARDIAL-INFARCTION; RHEUMATOID-ARTHRITIS; CLINICAL-TRIAL; CYCLO-OXYGENASE-2 INHIBITORS; CYCLOOXYGENASE-2 INHIBITORS; RISK; ETORICOXIB; METAANALYSIS; DICLOFENAC AB Introduction: The increased thrombotic cardiovascular (CV) risk in trials of cyclo-oxygenase-2 (COX-2) inhibitors versus placebo, and the apparent similar risk with nonsteroidal antiinflammatory drugs (NSAIDs), may be related to their potential to elevate blood pressure (BP). Aims: We evaluated the relationship between baseline BP and change in BP on CV events (CVEs) in patients receiving NSAIDs or COX-2 inhibitors in the prospective randomized, double-blind, Multinational Etoricoxib and Diclofenac Arthritis Long-term Program (N = 34,701) comparing etoricoxib 60 or 90 mg or diclofenac 150 mg daily for a mean duration of 18 months. The main outcome measure was confirmed thrombotic CVEs. The Antiplatelet Trialists Collaboration endpoint, all-cause mortality, CV/congestive heart failure (CHF) mortality, and CHF incidence were similarly evaluated. Results: We found that baseline systolic BP (SBP) was associated with significantly higher risk of all events (P < 0.001). Baseline diastolic BP (DBP) was inversely and significantly associated with risk of all events (P < 0.001 to P= 0.016) except CV/CHF mortality (P= 0.054). There was no significant differential effect between etoricoxib and diclofenac in relation to CVEs, except for confirmed CHF, for which the risk was significantly higher with etoricoxib (P= 0.019). Only CHF risk (P= 0.020 for both SBP and DBP change), but not thrombotic endpoints, was significantly associated with change in BP from months 0 to 4. These findings were not meaningfully altered after covariate adjustment for baseline CV risk. Conclusions: Baseline BP, but not change in BP, was significantly associated with risk of thrombotic CVEs through 18 months. The CV risk of COX-2s and NSAIDs did not appear to be related to the BP-elevating effects of these agents, although such analyses, i.e., from randomized controlled trials, are unable to definitively exclude such a relationship. C1 [Krum, Henry] Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. [Swergold, Gary] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Gammaitoni, Arnold; Peloso, Paul M.; Smugar, Steven S.; Curtis, Sean P.; Wang, Hongwei; Kaur, Amarjot] Merck Res Labs, Rahway, NJ USA. [Brater, D. Craig] Indiana Univ Sch Med, Indianapolis, IN USA. [Laine, Loren] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Weir, Matthew R.] Univ Maryland, Sch Med, Div Nephrol, Baltimore, MD 21201 USA. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Krum, H (reprint author), Monash Univ, Sch Publ Hlth & Prevent Med, Dept Epidemiol & Prevent Med, Ctr Cardiovasc Res & Educ Therapeut, Melbourne, Vic 3004, Australia. EM henry.krum@monash.edu FU Merck Research Laboratories; Pfizer; Bayer; Merck; Novartis; Accumetrics; AstraZeneca; Bristol-Myers Squibb; Glaxo Smith Kline; Interkin Therapeutics; Merck/Schering Plough Partnership; Takeda FX The original MEDAL program and the present analysis were funded by Merck Research Laboratories.; Henry Krum is on the advisory board for Merck. D. Craig Brater has served on the steering committee as a consultant for Merck. Matthew Weir is on the speaker's bureau for Merck and has acted as a consultant for Merck. Loren Laine has acted as a consultant for Merck, Novartis, and Bayer, and has received grants from Pfizer, Bayer, Merck, and Novartis. Christopher Cannon has received research grants from Accumetrics, AstraZeneca, Bristol-Myers Squibb, Glaxo Smith Kline, Interkin Therapeutics, Merck, Merck/Schering Plough Partnership, Novartis, and Takeda; and is a Clinical Advisor to and holds equity in Automedics Medical Systems. Arnold Gammaitoni, Paul Peloso, Sean Curtis, Amarjot Kaur, and Steven Smugar are current employees of Merck and may own or have options to earn company stock. Gary Swergold and Hongwei Wang are former employees of Merck. NR 35 TC 6 Z9 7 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5914 J9 CARDIOVASC THER JI Cardiovasc. Ther. PY 2012 VL 30 IS 6 BP 342 EP 350 DI 10.1111/j.1755-5922.2011.00283.x PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 034LF UT WOS:000310874000006 PM 21884017 ER PT J AU Zhu, ZL Li, GA AF Zhu, Zhonglin Li, Guoan TI An automatic 2D-3D image matching method for reproducing spatial knee joint positions using single or dual fluoroscopic images SO COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING LA English DT Article DE fluoroscopic image; in vivo knee kinematics; in vivo knee biomechanics; knee; computational biomechanics ID PLANE FLUOROSCOPY; REPLACEMENT KINEMATICS; REGISTRATION; VALIDATION; WEIGHT; MODELS; SYSTEM AB Fluoroscopic image technique, using either a single image or dual images, has been widely applied to measure in vivo human knee joint kinematics. However, few studies have compared the advantages of using single and dual fluoroscopic images. Furthermore, due to the size limitation of the image intensifiers, it is possible that only a portion of the knee joint could be captured by the fluoroscopy during dynamic knee joint motion. In this paper, we presented a systematic evaluation of an automatic 2D-3D image matching method in reproducing spatial knee joint positions using either single or dual fluoroscopic image techniques. The data indicated that for the femur and tibia, their spatial positions could be determined with an accuracy and precision less than 0.2 mm in translation and less than 0.4 degrees in orientation when dual fluoroscopic images were used. Using single fluoroscopic images, the method could produce satisfactory accuracy in joint positions in the imaging plane (in average up to 0.5 mm in translation and 1.3 degrees in rotation), but large variations along the out-plane direction (in average up to 4.0 mm in translation and 2.2 degrees in rotation). The precision of using single fluoroscopic images to determine the actual knee positions was worse than its accuracy obtained. The data also indicated that when using dual fluoroscopic image technique, if the knee joint outlines in one image were incomplete by 80%, the algorithm could still reproduce the joint positions with high precisions. C1 [Zhu, Zhonglin; Li, Guoan] Harvard Univ, Sch Med, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02115 USA. [Zhu, Zhonglin; Li, Guoan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhu, Zhonglin] Tsinghua Univ, Digital Med Engn Lab, Dept Biomed Engn, Beijing 100084, Peoples R China. RP Li, GA (reprint author), Harvard Univ, Sch Med, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02115 USA. EM gli1@partners.org FU National Institutes of Health [R01 AR055612]; China Scholarship Council [2010621146] FX The authors thank the technical assistant of Shaobai Wang, Jing-Sheng Li and Ali Hosseini. This study was partially supported by a grant from the National Institutes of Health (R01 AR055612) and a grant from the China Scholarship Council (2010621146). NR 18 TC 14 Z9 16 U1 1 U2 14 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-5842 J9 COMPUT METHOD BIOMEC JI Comput. Methods Biomech. Biomed. Eng. PY 2012 VL 15 IS 11 BP 1245 EP 1256 DI 10.1080/10255842.2011.597387 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical SC Computer Science; Engineering GA 032RH UT WOS:000310736300011 PM 21806411 ER PT J AU Wadsworth, LP Lorius, N Donovan, NJ Locascio, JJ Rentz, DM Johnson, KA Sperling, RA Marshall, GA AF Wadsworth, Lauren P. Lorius, Natacha Donovan, Nancy J. Locascio, Joseph J. Rentz, Dorene M. Johnson, Keith A. Sperling, Reisa A. Marshall, Gad A. CA Alzheimer's Dis Neuroimaging Initi TI Neuropsychiatric Symptoms and Global Functional Impairment along the Alzheimer's Continuum SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Alzheimer's disease; Anxiety; Apathy; Disease progression; Hallucinations; Mild cognitive impairment; Neuropsychiatric symptoms ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; NURSING-HOME PLACEMENT; PSYCHOLOGICAL SYMPTOMS; EXECUTIVE DYSFUNCTION; PROSPECTIVE COHORT; DISEASE; APATHY; DEMENTIA; PROGRESSION AB Background/Aims: Neuropsychiatric symptoms in Alzheimer's disease (AD) are highly prevalent. We sought to determine whether neuropsychiatric symptoms were related to global functional impairment at baseline and over a 3-year period in older normal control (NC), mild cognitive impairment (MCI) and mild AD dementia subjects. Methods: Eight hundred and twelve subjects (229 NC, 395 MCI, 188 AD) from the Alzheimer's Disease Neuroimaging Initiative study underwent cognitive and behavioral assessments over 3 years. Results: Greater hallucinations, anxiety and apathy were associated with greater global functional impairment at baseline, while the presence of hallucinations and apathy at baseline was associated with greater global functional impairment over time across all subjects. The following neuropsychiatric symptoms were not significantly associated with global functioning: delusions, agitation, depression, euphoria, disinhibition, irritability, aberrant motor behaviors, sleep and appetite. Conclusions: These results suggest that increased baseline hallucinations, apathy and anxiety are associated with current and future disease progression in AD. Copyright (C) 2012 S. Karger AG, Basel C1 [Lorius, Natacha; Donovan, Nancy J.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Wadsworth, Lauren P.; Lorius, Natacha; Locascio, Joseph J.; Rentz, Dorene M.; Sperling, Reisa A.; Marshall, Gad A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Donovan, Nancy J.] Cambridge Hlth Alliance, Dept Psychiat, Cambridge, MA USA. RP Marshall, GA (reprint author), Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, 221 Longwood Ave,BL-104H, Boston, MA 02115 USA. EM gamarshall@partners.org FU Rosalinde and Arthur Gilbert Foundation/American Federation for Aging Research New Investigator Awards in Alzheimer's Disease; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; Harvard Aging Brain Study [P01 AGO36694]; ADNI (National Institutes of Health) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; National Institutes of Health [P30 AG010129, K01 AG030514]; Dana Foundation; [R01 AG027435S]; [K23 AG033634]; [K24 AG035007] FX This study was supported by grants R01 AG027435S, K23 AG033634 and K24 AG035007, the Rosalinde and Arthur Gilbert Foundation/American Federation for Aging Research New Investigator Awards in Alzheimer's Disease, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134), the Harvard Aging Brain Study (P01 AGO36694) and the ADNI (National Institutes of Health grant U01 AG024904). The ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace Inc., Merck and Co. Inc., Novartis AG, Pfizer Inc., F. Hoffman-La Roche, Schering-Plough and Synarc Inc., as well as the nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of California, Los Angeles. This research was also supported by National Institutes of Health grants P30 AG010129 and K01 AG030514 and the Dana Foundation. NR 59 TC 44 Z9 46 U1 2 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2012 VL 34 IS 2 BP 96 EP 111 DI 10.1159/000342119 PG 16 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 036AF UT WOS:000310997000005 PM 22922821 ER PT J AU McDonald, LT LaRue, AC AF McDonald, Lindsay T. LaRue, Amanda C. TI Hematopoietic stem cell derived carcinoma-associated fibroblasts: a novel origin SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Review DE Hematopoietic stem cells; carcinoma associated fibroblasts; tumor associated fibroblasts; stem cell plasticity; tumor progression; metastasis ID PERIPHERAL-BLOOD FIBROCYTES; GROWTH-FACTOR-BETA; EPITHELIAL-MESENCHYMAL TRANSITION; CANCER-ASSOCIATED FIBROBLASTS; TUMOR-ASSOCIATED FIBROBLASTS; COLONY-STIMULATING FACTOR; PRIMARY MURINE STROMA; CIRCULATING FIBROCYTES; BREAST-CANCER; PROSTATE-CANCER AB Researchers have begun to appreciate the significant role that the microenvironment plays in tumorigenesis and are now shedding light on the role of the stroma in induction and progression of solid tumors. While the stroma of solid tumors is comprised of many cell types, including vascular and immune cells, one of the most prominent cell types in the tumor stroma is the fibroblast, called the carcinoma-associated fibroblast (CAF) or tumor-associated fibroblast (TAF). The interaction between CAFs and tumor cells is quite complex. CAFs have been implicated in tumor angiogenesis, immunosuppression, tumor cell proliferation and aggressiveness, genetic instability, and metastasis. However, their specific roles in each of these processes have only been partially elucidated. Determining the role of CAFs has been complicated by the fact that researchers have demonstrated heterogeneity in the stromal fibroblast population. This heterogeneity has brought about the concept of multiple origins for CAFs. While many origins of CAFs have been suggested, in our own laboratory we have identified a novel hematopoietic stem cell (HSC) origin of CAFs. Given the profound role of CAFs in tumor progression and prognosis, the CAF represents an exciting potential therapeutic target. The heterogeneity of the CAF population makes research directed at investigating the roles and origins of CAFs critical to development of such anti-tumor therapies. C1 [McDonald, Lindsay T.; LaRue, Amanda C.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29403 USA. [McDonald, Lindsay T.; LaRue, Amanda C.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [McDonald, Lindsay T.; LaRue, Amanda C.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. RP LaRue, AC (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Res Serv, 109 Bee St, Charleston, SC 29403 USA. EM laruerc@musc.edu FU Flow Cytometry and Cell Sorting Shared Resource; Cancer Center [P30 CA138313]; NIH/NCI [R01 CA148772]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; Hollings Cancer Center [P30 CA138313] FX The research presented in this article was supported in part by the Flow Cytometry and Cell Sorting Shared Resource, funded by a Cancer Center Support Grant P30 CA138313, to the Hollings Cancer Center at the Medical University of South Carolina. The authors would like to specifically thank Dr. Haiqun Zeng for assistance in FACS sorting reviewed in this manuscript. We also thank Ms. Dayvia A. Laws for her assistance in manuscript preparation. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government.; This work is supported in part by the NIH/NCI (R01 CA148772, ACL), the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs (Merit Award, ACL), and the Hollings Cancer Center (Translational Research Pilot Project, P30 CA138313, ACL). NR 77 TC 13 Z9 13 U1 0 U2 7 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1936-2625 J9 INT J CLIN EXP PATHO JI Int. J. Clin. Exp. Pathol. PY 2012 VL 5 IS 9 BP 863 EP 873 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA 033WN UT WOS:000310832200002 PM 23119103 ER PT J AU Yakoumakis, N Winey, B Killoran, J Mayo, C Niedermayr, T Panayiotakis, G Lingos, T Court, L AF Yakoumakis, Nikolaos Winey, Brian Killoran, Joseph Mayo, Charles Niedermayr, Thomas Panayiotakis, George Lingos, Tania Court, Laurence TI Using four-dimensional computed tomography images to optimize the internal target volume when using volume-modulated arc therapy to treat moving targets SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE treatment margins; ITV ID RESPIRATORY MOTION; RADIOTHERAPY; ERRORS; REGISTRATION AB In this work we used 4D dose calculations, which include the effects of shape deformations, to investigate an alternative approach to creating the ITV. We hypothesized that instead of needing images from all the breathing phases in the 4D CT dataset to create the outer envelope used for treatment planning, it is possible to exclude images from the phases closest to the inhale phase. We used 4D CT images from 10 patients with lung cancer. For each patient, we drew a gross tumor volume on the exhale-phase image and propagated this to the images from other phases in the 4D CT dataset using commercial image registration software. We created four different ITVs using the N phases closest to the exhale phase (where N = 10, 8, 7, 6). For each ITV contour, we created a volume-modulated arc therapy plan on the exhale-phase CT and normalized it so that the prescribed dose covered at least 95% of the ITV. Each plan was applied to CT images from each CT phase (phases 1-10), and the calculated doses were then mapped to the exhale phase using deformable registration. The effect of the motion was quantified using the dose to 95% of the target on the exhale phase (D-95) and tumor control probability. For the three-dimensional and 4D dose calculations of the plan where N = 10, differences in the D-95 value varied from 3% to 14%, with an average difference of 7%. For 9 of the 10 patients, the reduction in D-95 was less than 5% if eight phases were used to create the ITV. For three of the 10 patients, the reduction in the D-95 was less than 5% if seven phases were used to create the ITV. We were unsuccessful in creating a general rule that could be used to create the ITV. Some reduction (8/10 phases) was possible for most, but not all, of the patients, and the ITV reduction was small. C1 [Court, Laurence] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Unit 94, Houston, TX 77030 USA. [Yakoumakis, Nikolaos; Winey, Brian; Killoran, Joseph; Niedermayr, Thomas; Lingos, Tania] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Mayo, Charles] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. [Yakoumakis, Nikolaos] Univ Patras, Sch Med, Dept Med Phys, GR-26110 Patras, Greece. RP Court, L (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Unit 94, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM lecourt@mdanderson.org NR 12 TC 0 Z9 0 U1 0 U2 0 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2012 VL 13 IS 6 BP 181 EP 188 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 033ZW UT WOS:000310840900017 ER PT J AU Hinton, DE Hinton, AL Eng, KT Choung, S AF Hinton, Devon E. Hinton, Alexander L. Eng, Kok-Thay Choung, Sophearith TI PTSD and Key Somatic Complaints and Cultural Syndromes among Rural Cambodians: The Results of a Needs Assessment Survey SO MEDICAL ANTHROPOLOGY QUARTERLY LA English DT Article DE assessment; PTSD; somatization; cultural syndromes; Cambodia; dizziness ID POSTTRAUMATIC-STRESS-DISORDER; REFUGEES; DISTRESS; TRAUMA; SOMATIZATION; DEPRESSION; SURVIVORS; SYMPTOMS; VIOLENCE; ATTACKS AB This article describes a culturally sensitive assessment tool for traumatized Cambodians, the Cambodian "Somatic Symptom and Syndrome Inventory" (SSI), and reports the outcome of a needs assessment conducted in rural Cambodia using the instrument. Villagers locally identified (N = 139) as still suffering the effects of the Pol Pot genocide were evaluated. All 139 had post-traumatic stress disorder (PTSD) as assessed by the PTSD Checklist (PCL), and they had elevated SSI scores. The severity of the SSI items varied by level of PTSD severity, and several items-for example, dizziness, dizziness on standing, khyal (a windlike substance) attacks, and "thinking a lot"-were extremely elevated in those participants with higher levels of PTSD. The SSI was more highly correlated to self-perceived health (Short Form Health Survey-3) and past trauma events (Harvard Trauma Questionnaire) than was the PCL. The study shows the SSI items to be a core aspect of the Cambodian trauma ontology. C1 [Hinton, Devon E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hinton, Devon E.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Hinton, Alexander L.] Rutgers State Univ, Dept Anthropol, Piscataway, NJ 08855 USA. [Hinton, Alexander L.] Rutgers State Univ, Ctr Study Genocide Conflict Resolut & Human Right, Piscataway, NJ 08855 USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 46 TC 14 Z9 14 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0745-5194 J9 MED ANTHROPOL Q JI Med. Anthropol. Q. PY 2012 VL 26 IS 3 BP 383 EP 407 DI 10.1111/j.1548-1387.2012.01224.x PG 25 WC Anthropology; Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Anthropology; Public, Environmental & Occupational Health; Biomedical Social Sciences GA 026AB UT WOS:000310238900004 PM 23259349 ER PT S AU Ramos-Mendez, JA Perl, J Faddegon, B Paganetti, H AF Ramos-Mendez, J. A. Perl, J. Faddegon, B. Paganetti, H. BE Zamudio, FET Brandan, ME GamboadeBuen, I HerreraCorral, G MedinaVelazquez, LA TI Geometrical Splitting Technique To Improve The Computational Efficiency In Monte Carlo Calculations For Proton Therapy SO MEDICAL PHYSICS SE AIP Conference Proceedings LA English DT Proceedings Paper CT 12th Mexican Symposium on Medical Physics CY MAR 16-19, 2012 CL Hosp Reg Alta Especialidad Oaxaca (HRAEO), Oaxaca, MEXICO SP Soc Mexicana Fisica, Div Fisica Medica, Centro Latinoamericano Fisica (CLAF) HO Hosp Reg Alta Especialidad Oaxaca (HRAEO) DE Variance reduction; proton therapy; computational efficiency AB In this work, the well accepted particle splitting technique has been adapted to proton therapy and implemented in a new Monte Carlo simulation tool (TOPAS) for modeling the gantry mounted treatment nozzles at the Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital (MGH). Gains up to a factor of 14.5 in computational efficiency were reached with respect to a reference simulation in the generation of the phase space data in the cylindrically symmetric region of the nozzle. Comparisons between dose profiles in a water tank for several configurations show agreement between the simulations done with and without particle splitting within the statistical precision. C1 [Ramos-Mendez, J. A.] Benemerita Univ Autonoma Puebla, San Claudio Av, Puebla 72750, Mexico. [Perl, J.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA. [Faddegon, B.] Helen Diller Family Comprehens Canc Ctr, Dept Oncol Radiat, San Francisco, CA 94143 USA. [Paganetti, H.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Oncol Radiat, Boston, MA 02114 USA. RP Ramos-Mendez, JA (reprint author), Benemerita Univ Autonoma Puebla, San Claudio Av, Puebla 72750, Mexico. FU National Institutes of Health/National Cancer Institute (NIH/NCI) [R01 CA 140735-01.] FX This work was supported by National Institutes of Health/National Cancer Institute (NIH/NCI) under R01 CA 140735-01. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1106-7 J9 AIP CONF PROC PY 2012 VL 1494 BP 12 EP 15 DI 10.1063/1.4764586 PG 4 WC Engineering, Biomedical; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BCM03 UT WOS:000310678900003 ER PT J AU Ybarra, ML Bull, SS Kiwanuka, J Bangsberg, DR Korchmaros, J AF Ybarra, Michele L. Bull, Sheana S. Kiwanuka, Julius Bangsberg, David R. Korchmaros, Josephine TI Prevalence rates of sexual coercion victimization and perpetration among Uganda SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE coercive sex; adolescents; Uganda; developing country ID INTIMATE PARTNER VIOLENCE; SOUTH-AFRICA; REPRODUCTIVE HEALTH; CAPE-TOWN; WOMEN; ADOLESCENT; AGGRESSION; RISK; HIV; MEN AB Coercion is consistently reported as a risk factor for HIV in sub-Saharan Africa (SSA). Because of the gendered nature of previous research, however, little is known about male victims or female perpetrators. To address this gap, we report survey data from 354 sexually experienced secondary school students in Mbarara, Uganda. Findings suggest that females are more likely to report involvement in coercive sex compared to males (66% vs. 56%, respectively). Of those involved, females are most likely to report being a victim-only (40%) and males, perpetrator-victims (32%). Although involvement in violent and coercive sex is gendered, 47% of males report victim experiences and 25% of females report perpetration behavior. Furthermore, about one in ten female and male perpetrators reported using physical force or threats to compel sex. When all potentially influential factors were considered simultaneously, several characteristics seem to differentiate youth by their coercive sex (in) experience. For example, victims are more likely to have lower levels of social support from their families and feel that they have an above average or very strong chance of getting HIV compared to otherwise similar youth with no experience with coercive sex. Perpetrators are more likely to have had an HIV test but use condoms less than half the time or never compared to their otherwise similar, yet uninvolved peers. They also are significantly more likely to report dating violence perpetration. Perpetrator-victims share some similarities with other involved youth, as well as some differences. Findings underscore both the importance of asking all youth, irrespective of biological sex, perpetrator and victimization questions; and also the need for more work to be done to help youth plan for a healthy and wanted first sexual experience. C1 [Ybarra, Michele L.; Korchmaros, Josephine] Internet Solut Kids, San Clemente, CA USA. [Bull, Sheana S.] Univ Colorado Denver, Dept Community & Behav Hlth, Aurora, CO USA. [Kiwanuka, Julius] Mbarara Univ Sci & Technol, Dept Pediat, Mbarara, Uganda. [Bangsberg, David R.] Harvard Univ, Sch Med, Harvard Initiat Global Hlth, Massachusetts Gen Hosp,Ctr Global Hlth, Cambridge, MA 02138 USA. RP Ybarra, ML (reprint author), Internet Solut Kids, San Clemente, CA USA. EM Michele@IS4K.com FU NIMH NIH HHS [R01 MH080662, K24 MH087227, R01 MH054907, R01MH080662] NR 33 TC 7 Z9 7 U1 0 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2012 VL 24 IS 11 BP 1392 EP 1400 DI 10.1080/09540121.2011.648604 PG 9 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 029GV UT WOS:000310483700009 PM 22299764 ER PT J AU Thomas, B Mimiaga, MJ Mayer, KH Perry, NS Swaminathan, S Safren, SA AF Thomas, Beena Mimiaga, Matthew J. Mayer, Kenneth H. Perry, Nicholas S. Swaminathan, Soumya Safren, Steven A. TI The influence of stigma on HIV risk behavior among men who have sex with men in Chennai, India SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE men who have sex with men; MSM; depression; India; HIV; stigma ID BASE-LINE DATA; DEPRESSIVE SYMPTOMS; POSITIVE MEN; US CITIES; GAY MEN; PREVENTION; TRANSMISSION; EXPERIENCES; PREVALENCE; STRESSORS AB Stigma has been shown to increase vulnerability to HIV acquisition in many settings around the world. However, limited research has been conducted examining its role among men who have sex with men (MSM) in India, whose HIV prevalence is far greater than the general population. In 2009, 210 MSM in Chennai completed an interviewer-administered assessment, including questions about stigma, sexual risk, demographics, and psychosocial variables. More than one fifth of the MSM reported unprotected anal sex (UAS) in the past three months. Logistic regression procedures were used to examine correlates of having experienced stigma. The 11-item stigma scale had high internal consistency reliability (Cronbach's alpha = 0.99). Almost 2/5 (39%) reported a high-level of experienced stigma (>= 12 mean scale-score) in their lifetime, and the mean stigma scale score was 12 (SD = 2.0). Significant correlates of having experienced prior stigma, after adjusting for age and educational attainment, included the following: identifying as a kothi (feminine acting/appearing and predominantly receptive in anal sex) compared to a panthi (masculine appearing, predominantly insertive) (AOR = 63.23; 95% CI: 15.92-251.14; p < 0.0001); being "out" about one's MSM behavior (AOR = 5.63; 95% CI: 1.46-21.73; p = 0.01); having clinically significant depressive symptoms (AOR = 2.68; 95% CI: 1.40-5.12; p = 0.003); and engaging in sex work in the prior three months (AOR = 4.89; 95% CI: 2.51-9.51; p < 0.0001). These findings underscore the need to address psychosocial issues of Indian MSM. Unless issues such as stigma are addressed, effective HIV prevention interventions for this hidden population remain a challenge. C1 [Mimiaga, Matthew J.; Perry, Nicholas S.; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Thomas, Beena; Swaminathan, Soumya] Indian Council Med Res, TB Res Ctr, Madras, Tamil Nadu, India. [Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mimiaga, Matthew J.; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Dept Med & Community Hlth, Providence, RI 02906 USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM mmimiaga@partners.org FU NIAID NIH HHS [P30 AI060354]; NIMH NIH HHS [K24 MH094214]; PHS HHS [P30A1060354] NR 29 TC 16 Z9 17 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2012 VL 24 IS 11 BP 1401 EP 1406 DI 10.1080/09540121.2012.672717 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 029GV UT WOS:000310483700010 PM 22519945 ER PT J AU Chartier, M Carrico, AW Weiser, SD Kushel, MB Riley, ED AF Chartier, Maggie Carrico, Adam W. Weiser, Sheri D. Kushel, Margot B. Riley, Elise D. TI Specific psychiatric correlates of acute care utilization among unstably housed HIV-positive adults SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV/AIDS; homelessness; depression; stimulant abuse; healthcare utilization; acute care ID HEALTH-SERVICES UTILIZATION; SUBSTANCE-ABUSE TREATMENT; EMERGENCY-DEPARTMENT; CASE-MANAGEMENT; VULNERABLE POPULATIONS; HOMELESS PERSONS; RANDOMIZED-TRIAL; BEHAVIORAL-MODEL; MENTAL-HEALTH; HIV/AIDS AB The role of specific psychiatric diagnoses in emergency department use and/or inpatient hospitalizations (acute care) has not been extensively examined among HIV-infected, unstably housed persons. A community-recruited sample of 284 HIV-infected, unstably housed adults completed the Diagnostic Interview Schedule for DSM-IV. One-third of participants screened positive for major depression and stimulant use disorders. Sleeping on the street [adjusted odds ratio (AOR) = 4.21], major depression (AOR = 2.88) and stimulant use disorders (AOR = 4.45) were associated with greater odds of acute care use. Housing and effective treatment of depression and stimulant use disorders may decrease use of acute care services in this population. C1 [Chartier, Maggie] San Francisco VA Med Ctr, San Francisco, CA USA. [Chartier, Maggie] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Carrico, Adam W.; Weiser, Sheri D.] Univ Calif San Francisco, Sch Med, Ctr AIDS Prevent Studies, San Francisco, CA USA. [Carrico, Adam W.] Univ Calif San Francisco, Sch Nursing, Dept Community Hlth Syst, San Francisco, CA 94143 USA. [Weiser, Sheri D.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. [Kushel, Margot B.] UCSF San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA USA. [Riley, Elise D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Chartier, M (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA. EM maggie.chartier@ucsf.edu FU NCRR NIH HHS [UL1 RR024131]; NIDA NIH HHS [R01 DA015605, DA15605] NR 39 TC 3 Z9 3 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2012 VL 24 IS 12 BP 1514 EP 1518 DI 10.1080/09540121.2012.672720 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 029HA UT WOS:000310484200007 PM 22533713 ER PT J AU Epino, HM Rich, ML Kaigamba, F Hakizamungu, M Socci, AR Bagiruwigize, E Franke, MF AF Epino, Henry M. Rich, Michael L. Kaigamba, Felix Hakizamungu, Massudi Socci, Adrienne R. Bagiruwigize, Emmanuel Franke, Molly F. TI Reliability and construct validity of three health-related self-report scales in HIV-positive adults in rural Rwanda SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE Rwanda; HIV; depression; health-related quality of life; social support; validation ID SOCIAL SUPPORT; MEDICAL OUTCOMES; DEPRESSION; WOMEN; QUESTIONNAIRE; PREVALENCE; SYMPTOM; UGANDA AB Depression, low health-related quality of life, and low perceived social support have been shown to predict poor health outcomes, including HIV-related outcomes. Mental health morbidity and HIV are important public health concerns in Rwanda, where approximately half of the current population is estimated to have survived the genocide and 3% is living with HIV. We examined the reliability and construct validity of the Hopkins Symptom Checklist-15 (HSCL-15), the Medical Outcomes Study HIV Health Survey (MOS-HIV), and the Duke/UNC Functional Social Support Questionnaire (DUFSSQ), which were used to assess depression, health-related quality of life, and perceived social support, respectively, among HIV-infected adults in rural Rwanda. We also studied whether scale reliability differed by gender, literacy status, or antiretroviral therapy (ART) delivery strategy. The Kinyarwanda versions of the HSCL-15, MOS-HIV, and DUFSSQ performed well in the study population. Reliability was favorable (Cronbach's alpha coefficients >= 0.75 or above) for the scales overall and across subgroups of gender, literacy, and mode of ART delivery. The scales also demonstrated good convergent, discriminant, and known-group validity. C1 [Epino, Henry M.; Rich, Michael L.; Hakizamungu, Massudi; Socci, Adrienne R.; Franke, Molly F.] Partners Hlth Inshuti Mu Buzima, Rwinkwavu, Rwanda. [Epino, Henry M.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Epino, Henry M.; Rich, Michael L.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Kaigamba, Felix; Bagiruwigize, Emmanuel] Ruhengeri Hosp, Rwanda Minist Hlth, Ruhengeri, Rwanda. [Franke, Molly F.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. RP Epino, HM (reprint author), Partners Hlth Inshuti Mu Buzima, Rwinkwavu, Rwanda. EM hepino@pih.org NR 20 TC 11 Z9 11 U1 2 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2012 VL 24 IS 12 BP 1576 EP 1583 DI 10.1080/09540121.2012.661840 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 029HA UT WOS:000310484200014 PM 22428702 ER PT S AU Benjamin, DJ Cesarini, D Chabris, CF Glaeser, EL Laibson, DI Gudnason, V Harris, TB Launer, LJ Purcell, S Smith, AV Johannesson, M Magnusson, PKE Beauchamp, JP Christakis, NA Atwood, CS Hebert, B Freese, J Hauser, RM Hauser, TS Grankvist, A Hultman, CM Lichtenstein, P AF Benjamin, Daniel J. Cesarini, David Chabris, Christopher F. Glaeser, Edward L. Laibson, David I. Gudnason, Vilmundur Harris, Tamara B. Launer, Lenore J. Purcell, Shaun Smith, Albert Vernon Johannesson, Magnus Magnusson, Patrik K. E. Beauchamp, Jonathan P. Christakis, Nicholas A. Atwood, Craig S. Hebert, Benjamin Freese, Jeremy Hauser, Robert M. Hauser, Taissa S. Grankvist, Alexander Hultman, Christina M. Lichtenstein, Paul CA Age Gene Environm Swedish Twin Registry Framingham Heart Study Wisconsin Longitudinal Study Swedish Large Schizophrenia Study BE Arrow, KJ Bresnahan, TF TI The Promises and Pitfalls of Genoeconomics SO ANNUAL REVIEW OF ECONOMICS, VOL 4 SE Annual Review of Economics LA English DT Article; Book Chapter DE genetics; heritability; GWAS ID GENOME-WIDE ASSOCIATION; SEMIALDEHYDE DEHYDROGENASE-DEFICIENCY; BY-ENVIRONMENT INTERACTION; COMMON SNPS EXPLAIN; CANDIDATE GENE; COMPLEX TRAITS; FUNCTIONAL POLYMORPHISM; MENDELIAN RANDOMIZATION; PERSONALITY DIMENSIONS; RISK PREFERENCES AB This article reviews existing research at the intersection of genetics and economics, presents some new findings that illustrate the state of genoeconomics research, and surveys the prospects of this emerging field. Twin studies suggest that economic outcomes and preferences, once corrected for measurement error, appear to be about as heritable as many medical conditions and personality traits. Consistent with this pattern, we present new evidence on the heritability of permanent income and wealth. Turning to genetic association studies, we survey the main ways that the direct measurement of genetic variation across individuals is likely to contribute to economics, and we outline the challenges that have slowed progress in making these contributions. The most urgent problem facing researchers in this field is that most existing efforts to find associations between genetic variation and economic behavior are based on samples that are too small to ensure adequate statistical power. This has led to many false positives in the literature. We suggest a number of possible strategies to improve and remedy this problem: (a) pooling data sets, (b) using statistical techniques that exploit the greater information content of many genes considered jointly, and (c) focusing on economically relevant traits that are most proximate to known biological mechanisms. C1 [Benjamin, Daniel J.] Cornell Univ, Dept Econ, Ithaca, NY 14853 USA. [Benjamin, Daniel J.; Glaeser, Edward L.; Laibson, David I.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Cesarini, David] NYU, Ctr Expt Social Sci, New York, NY 10012 USA. [Cesarini, David] NYU, Dept Econ, New York, NY 10012 USA. [Chabris, Christopher F.] Union Coll, Dept Psychol, Schenectady, NY 12308 USA. [Glaeser, Edward L.; Laibson, David I.; Hebert, Benjamin] Harvard Univ, Dept Econ, Cambridge, MA 02138 USA. [Gudnason, Vilmundur; Smith, Albert Vernon] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Purcell, Shaun] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Johannesson, Magnus] Stockholm Sch Econ, Dept Econ, SE-11383 Stockholm, Sweden. [Magnusson, Patrik K. E.; Grankvist, Alexander; Hultman, Christina M.; Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. [Beauchamp, Jonathan P.] McKinsey Consulting, Montreal, PQ H3B 4W8, Canada. [Christakis, Nicholas A.] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA. [Christakis, Nicholas A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Atwood, Craig S.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Freese, Jeremy] Northwestern Univ, Dept Sociol, Evanston, IL 60208 USA. [Hauser, Robert M.; Hauser, Taissa S.] Univ Wisconsin, Dept Sociol, Madison, WI 53706 USA. RP Benjamin, DJ (reprint author), Cornell Univ, Dept Econ, Ithaca, NY 14853 USA. EM db468@cornell.edu RI Johannesson, Magnus/E-9680-2011; Gudnason, Vilmundur/K-6885-2015; Smith, Albert/K-5150-2015; Magnusson, Patrik/C-4458-2017; OI Johannesson, Magnus/0000-0001-8759-6393; lichtenstein, paul/0000-0003-3037-5287; Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845; Cesarini, David/0000-0002-0043-009X FU NIA NIH HHS [P01 AG005842, T32 AG000186] NR 117 TC 43 Z9 43 U1 4 U2 40 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1941-1383 BN 978-0-8243-4604-1 J9 ANNU REV ECON JI Annu. Rev. Econ. PY 2012 VL 4 BP 627 EP + DI 10.1146/annurev-economics-080511-110939 PG 37 WC Economics SC Business & Economics GA BCG24 UT WOS:000310144600023 PM 23482589 ER PT J AU Zhang, ZJ Kwiatkowski, N Zeng, H Lim, SM Gray, NS Zhang, W Yang, PL AF Zhang, Zijuan Kwiatkowski, Nicholas Zeng, Hong Lim, Sang Min Gray, Nathanael S. Zhang, Wei Yang, Priscilla L. TI Leveraging kinase inhibitors to develop small molecule tools for imaging kinases by fluorescence microscopy SO MOLECULAR BIOSYSTEMS LA English DT Article ID POLO-LIKE KINASES; DNA STRAND BREAKS; BOX DOMAIN; PLK1; BODIPY; PHOSPHORYLATION; CYTOKINESIS; CHECKPOINT; MPS1; APOPTOSIS AB As the usage of fluorescence microscopy as a tool to study biological systems continues to grow, so does the need for additional tools that permit the selective detection of proteins of interest. Existing selective and well-characterized kinase inhibitors may be exploited to develop novel small molecule probes useful in imaging kinases by fluorescence microscopy. C1 [Yang, Priscilla L.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02115 USA. [Zhang, Zijuan; Zeng, Hong; Zhang, Wei] Univ Massachusetts, Dept Chem, Boston, MA 02125 USA. [Kwiatkowski, Nicholas; Lim, Sang Min; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Kwiatkowski, Nicholas; Lim, Sang Min; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Yang, PL (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, 200 Longwood Ave, Boston, MA 02115 USA. EM wei2.zhang@umb.edu; nathanael_gray@dfci.harvard.edu; priscilla_yang@hms.harvard.edu FU National Institutes of Health/National Cancer Institute [U54 CA156732]; NIH/NIAID [AI076442] FX This work was supported by the National Institutes of Health/National Cancer Institute grant U54 CA156732 to the University of Massachusetts Boston - Dana-Farber Harvard Cancer Center (UMB-DFHCC) U54 Comprehensive Partnership to Reduce Cancer Health Disparities (Project 3, Co-PIs: N. S. Gray, W. Zhang, and P. L. Yang) and by NIH/NIAID AI076442 (PI: P. L. Yang). NR 31 TC 12 Z9 12 U1 0 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2012 VL 8 IS 10 BP 2523 EP 2526 DI 10.1039/c2mb25099c PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 996OB UT WOS:000308098600007 PM 22673640 ER PT J AU Choi, SY Fogelgren, B Zuo, XF Huang, LW McKenna, S Lingappa, VR Lipschutz, JH AF Choi, Soo Young Fogelgren, Ben Zuo, Xiaofeng Huang, Liwei McKenna, Sarah Lingappa, Vishwanath R. Lipschutz, Joshua H. TI Exocyst Sec10 Is Involved in Basolateral Protein Translation and Translocation in the Endoplasmic Reticulum SO NEPHRON EXPERIMENTAL NEPHROLOGY LA English DT Article DE Exocyst; Polarity; Translation; Endoplasmic reticulum ID SECRETORY PROTEINS; PRIMARY CILIOGENESIS; PLASMA-MEMBRANE; SEC6/8 COMPLEX; BETA-SUBUNIT; MDCK CELLS; CYSTOGENESIS; COMPONENTS; INTERACTS; DELIVERY AB Background: Protein translation and translocation at the rough endoplasmic reticulum (RER) are the first steps in the secretory pathway. The translocon through which newly made proteins are translocated into or across the RER membrane consists of three main subunits: Sec61 alpha, -beta, and -gamma. Sec61 beta facilitates translocation, and we and others have shown that the highly conserved eight-protein exocyst complex interacts with Sec61 beta. We have also shown that the exocyst is involved in basolateral, not apical, protein synthesis and delivery. Recently, however, exocyst involvement in apical protein delivery has been reported. Furthermore, we have shown that the exocyst is necessary for formation of primary cilia, organelles found on the apical surface. Methods: GST pulldown was performed on lysate of renal tubule cells to investigate biochemical interactions. Cell-free assays consisting of cell-free extracts from rabbit reticulocytes, pancreatic endoplasmic reticulum (ER) microsomal membranes, transcripts of cDNA from apical and basolateral proteins, ATP/GTP, amino acids, and S-35-methionine for protein detection were used to investigate the role of the exocyst in synthesis of polarized proteins. P-32-orthophosphate and immunoprecipitation with antibody against Sec61 beta was used to investigate Sec61 beta phosphorylation in exocyst Sec10-overexpressing cells. Results: Sec10 biochemically interacts with Sec61 beta using GST pulldown. Using cell-free assays, there is enhanced exocyst recruitment to endoplasmic reticulum membranes following exocyst depletion and basolateral G protein of vesicular stomatitis virus protein translation, compared to apical hemagglutinin of influenza virus protein translation. Finally, Sec10 overexpression increases Sec61 beta phosphorylation. Conclusion: These data confirm that the exocyst is preferentially involved in basolateral protein translation and translocation, and may well act through the phosphorylation of Sec61 beta. Copyright (C) 2012 S. Karger AG, Basel C1 [Lipschutz, Joshua H.] Univ Penn, Renal Electrolyte & Hypertens Div, Dept Med, Philadelphia, PA 19104 USA. [Lipschutz, Joshua H.] Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. [Lingappa, Vishwanath R.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA USA. [Lingappa, Vishwanath R.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Lipschutz, JH (reprint author), Univ Penn, Renal Electrolyte & Hypertens Div, Dept Med, Clin Res Bldg,Room 538A,415 Curie Blvd, Philadelphia, PA 19104 USA. EM jhlipsch@mail.med.upenn.edu FU VA (Merit Award); NIH [DK069909, DK047757, K01DK087852, K08DK093625]; University of Pennsylvania Research Foundation; Satellite Healthcare FX This work was supported in part by grants from the VA (Merit Award to J.H.L.), NIH (DK069909 and DK047757 to J.H.L.; K01DK087852 to B. F., K08DK093625 to L. H.), University of Pennsylvania Research Foundation (to J.H.L.), and Satellite Healthcare (Norman S. Coplon Extramural Research Grant to J.H.L.). NR 25 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2129 J9 NEPHRON EXP NEPHROL JI Nephron Exp. Nephrol PY 2012 VL 120 IS 4 BP E133 EP E139 DI 10.1159/000342366 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 030NE UT WOS:000310576600003 PM 23037926 ER PT J AU Mills, KA Scherzer, R Starr, PA Ostrem, JL AF Mills, Kelly A. Scherzer, Rebecca Starr, Philip A. Ostrem, Jill L. TI Weight Change after Globus Pallidus Internus or Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease and Dystonia SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE Deep brain stimulation; Parkinson's disease; Dystonia; Subthalamic nucleus; Globus pallidus internus; Weight change ID BODY-WEIGHT; ESSENTIAL TREMOR; THALAMIC-STIMULATION; GAIN; SURGERY; PALLIDOTOMY; EFFICACY; SAFETY AB Background: Weight gain has been described in Parkinson's disease (PD) patients after subthalamic nucleus (STN) deep brain stimulation (DBS). Objectives: We examined change in weight following DBS in both PD and dystonia patients to further investigate the role of disease and brain target (STN or globus pallidus internus, GPi) specificity. Methods: Data was retrospectively collected on 61 PD DBS patients (STN n = 31 or GPi n = 30) and on 36 dystonia DBS patients (STN n = 9 and GPi n = 27) before and after surgery. Annual change in body mass index (BMI) was evaluated with nonparametric tests between groups and multiple quantile regression. Results: PD patients treated with STN DBS had a small increase in median BMI while those with GPi had a small decrease in BMI. Dystonia patients treated with STN DBS had a greater increase in BMI per year compared to those treated with GPi DBS. Multivariable regression analyses for each disease showed little difference between targets in weight gain in those with PD, but STN target was strongly associated with weight gain in dystonia patients (STN vs. GPi, +7.99 kg, p = 0.012). Conclusions: Our results support previous reports of weight gain after DBS in PD. This is the first report to suggest a target-specific increase in weight following STN DBS in dystonia patients. Copyright (C) 2012 S. Karger AG, Basel C1 [Mills, Kelly A.; Ostrem, Jill L.] Univ Calif San Francisco, Surg Movement Disorders Ctr, Dept Neurol, San Francisco, CA 94115 USA. [Starr, Philip A.] Univ Calif San Francisco, Surg Movement Disorders Ctr, Dept Neurosurg, San Francisco, CA 94115 USA. [Scherzer, Rebecca] Univ Calif San Francisco, Dept Med, San Francisco, CA 94115 USA. [Mills, Kelly A.; Scherzer, Rebecca; Starr, Philip A.; Ostrem, Jill L.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Ostrem, JL (reprint author), Univ Calif San Francisco, Surg Movement Disorders Ctr, Dept Neurol, 1635 Divisadero St,Suite 502, San Francisco, CA 94115 USA. EM jill.ostrem@ucsf.edu FU University of California San Francisco Clinical and Translational Science Institute Resident Research Funding Award; Clinical and Translational Science Institute Strategic Opportunities Support Novel Clinical/Translational Methods Catalyst Awards; NIH/NCRR UCSF-CTSI [UL1RR024131]; MRI Interventions Inc.; St. Jude Medical; Medtronic Inc. FX Kelly Mills is funded by the University of California San Francisco Clinical and Translational Science Institute Resident Research Funding Award, he is also Co-PI on a grant from the Clinical and Translational Science Institute Strategic Opportunities Support Novel Clinical/Translational Methods Catalyst Awards, NIH/NCRR UCSF-CTSI grant No. UL1RR024131. Philip Starr is a consultant for Medtronic Inc. and Boston Scientific Inc. and holds a research grant from MRI Interventions Inc. (formerly called Surgivision). Jill Ostrem is a consultant for Ipsen Inc., Merz Inc., Boston Scientific Inc. and is on an advisory board for Ipsen Inc. and Merz Inc. She has received honoraria from Medtronic Inc. and Allergan Inc. and currently receives research grant funding from St. Jude Medical and MRI Interventions Inc. (formally called SurgiVision). She is also mentor for a fellowship grant from Medtronic Inc. NR 31 TC 15 Z9 15 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2012 VL 90 IS 6 BP 386 EP 393 DI 10.1159/000340071 PG 8 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 027MU UT WOS:000310357500007 PM 22922491 ER PT J AU Weller, DS Polimeni, JR Grady, L Wald, LL Adalsteinsson, E Goyal, VK AF Weller, Daniel S. Polimeni, Jonathan R. Grady, Leo Wald, Lawrence L. Adalsteinsson, Elfar Goyal, Vivek K. GP IEEE TI ACCELERATED PARALLEL MAGNETIC RESONANCE IMAGING RECONSTRUCTION USING JOINT ESTIMATION WITH A SPARSE SIGNAL MODEL SO 2012 IEEE STATISTICAL SIGNAL PROCESSING WORKSHOP (SSP) LA English DT Proceedings Paper CT IEEE Statistical Signal Processing Workshop (SSP) CY AUG 05-08, 2012 CL Ann Arbor, MI SP IEEE DE Magnetic resonance imaging; image reconstruction; parallel imaging; sparsity; Bayesian estimation ID LEAST-SQUARES; SENSE; MRI AB Accelerating magnetic resonance imaging (MRI) by reducing the number of acquired k-space scan lines benefits conventional MRI significantly by decreasing the time subjects remain in the magnet. In this paper, we formulate a novel method for Joint estimation from Undersampled LinEs in Parallel MRI (JULEP) that simultaneously calibrates the GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) reconstruction kernel and reconstructs the full multi-channel k-space. We employ a joint sparsity signal model for the channel images in conjunction with observation models for both the acquired data and GRAPPA reconstructed k-space. We demonstrate using real MRI data that JULEP outperforms conventional GRAPPA reconstruction at high levels of undersampling, increasing the peak-signal-to-noise ratio by up to 10 dB. C1 [Weller, Daniel S.; Adalsteinsson, Elfar; Goyal, Vivek K.] MIT, Dept EECS, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Polimeni, Jonathan R.; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr, Charlestown, MA USA. [Grady, Leo] Siemens Corp Res, Dept Image Analyt & Informat, Princeton, NJ USA. RP Weller, DS (reprint author), MIT, Dept EECS, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM dweller@mit.edu; jonp@nmr.mgh.harvard.edu; leo.grady@siemens.com; wald@nmr.mgh.harvard.edu; elfar@mit.edu; vgoyal@mit.edu RI Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Polimeni, Jonathan/0000-0002-1348-1179; FU NSF CAREER [CCF-0643836]; NIH [R01 EB007942, EB006847, NIH NCRR P41 RR014075]; Siemens Corporate Research; NSF Graduate Research Fellowship FX Funding acknowledgments: NSF CAREER Grant CCF-0643836, NIH R01 EB007942 and EB006847, NIH NCRR P41 RR014075, Siemens Corporate Research, and an NSF Graduate Research Fellowship. NR 12 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-0183-1 PY 2012 BP 221 EP 224 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA BCE18 UT WOS:000309943200056 ER PT S AU Pfab, F Valet, M Napadow, V Tolle, TR Behrendt, H Ring, J Darsow, U AF Pfab, F. Valet, M. Napadow, V. Toelle, T-R Behrendt, H. Ring, J. Darsow, U. BE Bienenstock, J TI Itch and the Brain SO ALLERGY AND THE NERVOUS SYSTEM SE Chemical Immunology and Allergy LA English DT Article; Book Chapter ID HISTAMINE-INDUCED ITCH; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; HUMAN CEREBRAL-CORTEX; ATOPIC-DERMATITIS; NEURAL RESPONSES; PAIN; FMRI; DISEASE; SKIN AB The sensation of itch defined as unpleasant sensation inducing the urge to scratch is processed by a network of different brain regions contributing to the encoding of sensory, emotional, attention-dependent, cognitive-evaluative and motivational patterns. Patients with atopic eczema show different activation patterns and kinetics compared to healthy volunteers. This review summarizes current studies investigating itch in the brain. (C) 2012 S. Karger AG, Basel C1 [Pfab, F.; Napadow, V.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Pfab, F.; Ring, J.; Darsow, U.] Tech Univ Munich, Dept Dermatol & Allergy, Klinikum Rd Isar, Munich, Germany. [Valet, M.; Toelle, T-R; Darsow, U.] Tech Univ Munich, Dept Neurol, Klinikum Rd Isar, Munich, Germany. [Behrendt, H.; Ring, J.] Helmholtz Zentrum Munchen TUM, ZAUM Ctr Allergy & Environm, Div Environm Dermatol & Allergy, Munich, Germany. RP Pfab, F (reprint author), Harvard Univ, Dept Radiol, Massachusetts Gen Hosp, Sch Med, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. EM pfab@nmr.mgh.harvard.edu NR 36 TC 12 Z9 13 U1 0 U2 10 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1660-2242 BN 978-3-8055-9984-9 J9 CHEM IMMUNOL ALLERGY JI Chem. Immunol. Allergy PY 2012 VL 98 BP 253 EP 265 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA BBH16 UT WOS:000306817500016 PM 22767068 ER PT S AU Schneider, JA Montine, TJ Sperling, RA Bennett, DA AF Schneider, Julie A. Montine, Thomas J. Sperling, Reisa A. Bennett, David A. BE Hampel, H Carrillo, MC TI Neuropathological Basis of Alzheimer's Disease and Alzheimer's Disease Diagnosis SO ALZHEIMER'S DISEASE - MODERNIZING CONCEPT, BIOLOGICAL DIAGNOSIS AND THERAPY SE Advances in Biological Psychiatry LA English DT Article; Book Chapter ID MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID BIOMARKERS; PITTSBURGH COMPOUND-B; CEREBRAL GREY MATTER; DEMENTED OLD PEOPLE; BETA-AMYLOID LOAD; A-BETA; SENILE-DEMENTIA; ASSOCIATION WORKGROUPS; NATIONAL INSTITUTE AB Great strides in the understanding of the neuropathologic basis of Alzheimer's disease (AD) have been achieved over the past century. An overview of the history, current understanding and recent advances in the neuropathologic basis of AD are highlighted in this chapter. Recent advances include the conceptualization and study of the preclinical phase of AD, mild cognitive impairment, mixed pathologies, and the specific roles of beta-amyloid and hyperphosphorylated tau protein, as well as other protein accumulations such as soluble amyloid and TDP-43. Furthermore, cerebrospinal fluid and imaging biomarkers in symptomatic and presymptomatic disease are emerging as exciting new tools for both clinical practice and research. These and other advances have led to the formation of new clinical criteria followed by new pathologic criteria for the diagnosis of AD. These advances are likely to have a profound impact on the direction of future research on the prevention and treatment of AD. Copyright (C) 2012 S. Karger AG, Basel C1 [Schneider, Julie A.] Rush Univ, Ctr Med, Rush Alzheimers Dis Ctr, Armour Acad Ctr,Dept Pathol Neuropathol & Neurol, Chicago, IL 60612 USA. [Schneider, Julie A.; Bennett, David A.] Rush Univ, Ctr Med, Dept Neurol Sci, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Ctr Med, Dept Pathol Neuropathol, Chicago, IL 60612 USA. [Montine, Thomas J.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol,Massachusetts Gen Hosp,Med Sch, Boston, MA 02115 USA. RP Schneider, JA (reprint author), Rush Univ, Ctr Med, Rush Alzheimers Dis Ctr, Armour Acad Ctr,Dept Pathol Neuropathol & Neurol, 600 S Paulina St,Suite 1022F, Chicago, IL 60612 USA. EM julie_a_schneider@rush.edu NR 132 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0378-7354 BN 978-3-8055-9802-6 J9 ADV BIOL PSYCH-KARG JI Adv.Biol.Psychiatry PY 2012 VL 28 BP 49 EP 70 PG 22 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BBI12 UT WOS:000306935400004 ER PT S AU Teipel, S Sperling, RA Skudlarski, P Jack, C Hampel, H Fellgiebel, A Herholz, K AF Teipel, Stefan Sperling, Reisa A. Skudlarski, Pawel Jack, Clifford Hampel, Harald Fellgiebel, Andreas Herholz, Karl BE Hampel, H Carrillo, MC TI MRI- and PET-Based Imaging Markers for the Diagnosis of Alzheimer's Disease SO ALZHEIMER'S DISEASE - MODERNIZING CONCEPT, BIOLOGICAL DIAGNOSIS AND THERAPY SE Advances in Biological Psychiatry LA English DT Article; Book Chapter ID MILD COGNITIVE IMPAIRMENT; MEDIAL TEMPORAL-LOBE; VOXEL-BASED MORPHOMETRY; PITTSBURGH COMPOUND-B; GRAY-MATTER LOSS; INDEPENDENT COMPONENT ANALYSIS; DEFAULT-MODE NETWORK; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL AMYLOID ANGIOPATHY; APOLIPOPROTEIN-E EPSILON-4 AB Imaging markers of early neurodegeneration play an important role for the definition of predementia and preclinical stages of Alzheimer's disease according to the newly proposed diagnostic consensus criteria. Markers of regional and global brain atrophy in MRI and the detection of cortical metabolic decline and cerebral amyloid deposition using PET are the best established imaging markers for prodromal and clinical Alzheimer's disease to date. Detection of structural and functional cortical disconnection using functional MRI and diffusion tensor imaging add to the diagnostic sensitivity and specificity. Important areas of future research are the application of imaging markers in large multicenter studies, and their implementation in radiological expert systems for diagnosis. Additionally, we need to consider the effect of these new markers on care for patients and counseling of at-risk subjects. Copyright (C) 2012 S. Karger AG, Basel C1 [Teipel, Stefan] Univ Rostock, Dept Psychiat, DE-18147 Rostock, Germany. [Teipel, Stefan] German Ctr Neurodegenerat Dis, DZNE, DE-18147 Rostock, Germany. [Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol,Massachusetts Gen Hosp,Med Sch, Boston, MA 02115 USA. [Skudlarski, Pawel] IOL, Hartford Hosp, Olin Neuropsychiat Res Ctr, Hartford, CT USA. [Jack, Clifford] Mayo Clin, Dept Radiol, Rochester, MN USA. [Hampel, Harald] Goethe Univ Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany. [Fellgiebel, Andreas] Johannes Gutenberg Univ Mainz, Dept Psychiat, D-6500 Mainz, Germany. [Herholz, Karl] Univ Manchester, Manchester, Lancs, England. RP Teipel, S (reprint author), Univ Rostock, Dept Psychiat, Gehlsheimer Str 20, DE-18147 Rostock, Germany. EM stefan.teipel@med.uni-rostock.de NR 282 TC 1 Z9 1 U1 3 U2 5 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0378-7354 BN 978-3-8055-9802-6 J9 ADV BIOL PSYCH-KARG JI Adv.Biol.Psychiatry PY 2012 VL 28 BP 80 EP 114 PG 35 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA BBI12 UT WOS:000306935400006 ER PT J AU McCarthy, DM Gioioso, V Zhang, X Sharma, N Bhide, PG AF McCarthy, Deirdre M. Gioioso, Valeria Zhang, Xuan Sharma, Nutan Bhide, Pradeep G. TI Neurogenesis and Neuronal Migration in the Forebrain of the TorsinA Knockout Mouse Embryo SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Dystonia; DYT1; Medial ganglionic eminence; Nkx2-1 ID DYT1 DYSTONIA MUTATION; CELL-CYCLE; NUCLEAR-ENVELOPE; DEVELOPING NEOCORTEX; SYNAPTIC PLASTICITY; PROGENITOR CELLS; CEREBRAL-CORTEX; MOTOR DEFICITS; NEURAL STEM; MODEL AB Early-onset generalized torsion dystonia, also known as DYT1 dystonia, is a childhood onset heritable neurological movement disorder involving painful, involuntary muscle contractions, sustained abnormal postures, and repetitive movements. It is caused by a GAG deletion in the Tor1A gene located on chromosome 9. TorsinA, the product of the Tor1A gene, is expressed throughout the brain beginning early in embryonic development. It plays a role in the regulation of nuclear envelope-cytoskeletal interactions, and presumably nuclear translocation. Since nuclear translocation, powered by cytoskeletal traction, is critical for cell proliferation and migration, we examined whether neurogenesis and neuronal migration are affected in Tor1A-/- mouse brain. Our data show that interkinetic nuclear migration and the pattern of migration of newly generated neurons are impaired in the dorsal forebrain of the Tor1A-/- embryo. However, neurogenesis is not altered significantly. The rate of migration of cells from explants of the medial ganglionic eminence is also impaired in the Tor1A-/- embryo. Thus, loss of torsinA results in subtle but significant alterations in cell proliferation and migration in the embryonic forebrain. These subtle developmental changes are consistent with a lack of significant changes in neuronal numbers, neuronal positioning or size of brain regions in DYT1 dystonia patients. Copyright (C) 2012 S. Karger AG, Basel C1 [McCarthy, Deirdre M.; Zhang, Xuan; Bhide, Pradeep G.] Florida State Univ, Coll Med, Dept Biomed Sci, Tallahassee, FL 32303 USA. [McCarthy, Deirdre M.; Gioioso, Valeria; Sharma, Nutan; Bhide, Pradeep G.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [McCarthy, Deirdre M.; Gioioso, Valeria; Sharma, Nutan; Bhide, Pradeep G.] Harvard Univ, Sch Med, Charlestown, MA USA. RP Bhide, PG (reprint author), Florida State Univ, Coll Med, Dept Biomed Sci, 1115 W Call St, Tallahassee, FL 32303 USA. EM Pradeep.Bhide@med.fsu.edu OI Bhide, Pradeep/0000-0003-4236-9415 FU USPHS [P50 NS037409, P30NS045776] FX This work was supported by USPHS grants P50 NS037409 and P30NS045776. We are grateful to Igor Bagayev of the Massachusetts General Hospital confocal microscope facility for expert assistance with confocal microscopy and to the staff of the Massachusetts General Hospital's Center for Comparative Medicine for expert assistance with mouse colony management. NR 77 TC 9 Z9 9 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2012 VL 34 IS 4 BP 366 EP 378 DI 10.1159/000342260 PG 13 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 024IG UT WOS:000310102300008 PM 23018676 ER PT J AU Tranah, GJ Nalls, MA Katzman, SM Yokoyama, JS Lam, ET Zhao, YQ Mooney, S Thomas, F Newman, AB Liu, YM Cummings, SR Harris, TB Yaffe, K AF Tranah, Gregory J. Nalls, Michael A. Katzman, Shana M. Yokoyama, Jennifer S. Lam, Ernest T. Zhao, Yiqiang Mooney, Sean Thomas, Fridtjof Newman, Anne B. Liu, Yongmei Cummings, Steven R. Harris, Tamara B. Yaffe, Kristine CA Hlth Aging & Body Composition Stud TI Mitochondrial DNA Sequence Variation Associated with Dementia and Cognitive Function in the Elderly SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Cognitive function; dementia; DNA sequencing; mitochondria; mtDNA; oxidative phosphorylation ID GENOME-WIDE ASSOCIATION; ALPHA-KETOGLUTARATE DEHYDROGENASE; CYTOCHROME-C-OXIDASE; HUMAN SUBSTANTIA-NIGRA; ACTIVITY ENERGY-EXPENDITURE; AMYLOID PRECURSOR PROTEIN; AMINO-ACID SUBSTITUTIONS; INDUCED OXIDATIVE STRESS; HUMAN SKELETAL-MUSCLE; ALZHEIMERS-DISEASE AB Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). Mitochondrial DNA (mtDNA) damage may be a major cause of abnormal reactive oxidative species production in AD or increased neuronal susceptibility to oxidative injury during aging. The purpose of this study was to assess the influence of mtDNA sequence variation on clinically significant cognitive impairment and dementia risk in the population-based Health, Aging, and Body Composition (Health ABC) Study. We first investigated the role of common mtDNA haplogroups and individual variants on dementia risk and 8-year change on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) among 1,631 participants of European genetic ancestry. Participants were free of dementia at baseline and incidence was determined in 273 cases from hospital and medication records over 10-12 follow-up years. Participants from haplogroup T had a statistically significant increased risk of developing dementia (OR = 1.86, 95% CI = 1.23, 2.82, p = 0.0008) and haplogroup J participants experienced a statistically significant 8-year decline in 3MS (beta = -0.14, 95% CI = -0.27, -0.03, p = 0.0006), both compared with common haplogroup H. The m. 15244A>G, p.G166G, CytB variant was associated with a significant decline in DSST score (beta = -0.58, 95% CI -0.89, -0.28, p = 0.00019) and the m.14178T>C, p.I166V, ND6 variant was associated with a significant decline in 3MS score (beta = -0.87, 95% CI-1.31, -3.86, p = 0.00012). Finally, we sequenced the complete similar to 16.5 kb mtDNA from 135 Health ABC participants and identified several highly conserved and potentially functional nonsynonymous variants unique to 22 dementia cases and aggregate sequence variation across the hypervariable 2-3 regions that influences 3MS and DSST scores. C1 [Tranah, Gregory J.] UCSF, Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, San Francisco, CA 94107 USA. [Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Katzman, Shana M.; Zhao, Yiqiang; Mooney, Sean] Buck Inst Res Aging, Novato, CA USA. [Yokoyama, Jennifer S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Lam, Ernest T.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Thomas, Fridtjof] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Tranah, GJ (reprint author), UCSF, Calif Pacific Med Ctr, Res Inst, San Francisco Coordinating Ctr, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA. EM gtranah@sfcc-cpmc.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Institute on Aging (NIA) [N01 AG62101, N01 AG62103, N01 AG62106, R01 AG028050, R03 AG032498, 1R01 AG032098-01A1]; NINR [R01 NR012459, Z01 AG000951]; NIH [T32 GM007175]; NLM [LM009722]; Intramural Research Program of the NIH, NIA; National Institutes of Health [HHSN268200782096C] FX This research was supported by National Institute on Aging (NIA) Contracts N01 AG62101; N01 AG62103; N01 AG62106; NIA grants R01 AG028050 and R03 AG032498, NINR grant R01 NR012459; and Z01 AG000951. E. T. L. was supported in part by NIH Training Grant T32 GM007175 and Y.Z. by NLM grant LM009722. This research was supported in part by the Intramural Research Program of the NIH, NIA. The genome-wide association study was funded by NIA grant 1R01 AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to Johns Hopkins University, contract number HHSN268200782096C. Data analyses for this study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, Maryland (http://biowulf.nih.gov). NR 170 TC 9 Z9 9 U1 3 U2 15 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 32 IS 2 BP 357 EP 372 DI 10.3233/JAD-2012-120466 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 022QY UT WOS:000309977800010 PM 22785396 ER PT J AU Farr, SA Price, TO Banks, WA Ercal, N Morley, JE AF Farr, Susan A. Price, Tulin O. Banks, William A. Ercal, Nuran Morley, John E. TI Effect of Alpha-Lipoic Acid on Memory, Oxidation, and Lifespan in SAMP8 Mice SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alpha-lipoic acid; antioxidants; learning and memory; lifespan; SAMP8 mice ID SENESCENCE-ACCELERATED MOUSE; AGING RAT-HEART; ALZHEIMERS-DISEASE; BRAIN PROTEINS; C57BL/6 MICE; STRESS; DAMAGE; SUPPLEMENTATION; ANTIOXIDANTS; EXPRESSION AB Oxidative damage is associated with neurodegenerative disorders such as Alzheimer's disease (AD). The antioxidant alpha-lipoic acid has been found to improve memory in mouse models of AD. Here, we administered alpha-lipoic acid daily to SAMP8 mice starting at 11 months of age and continuing until death. We found that treatment with alpha-lipoic acid decreased survival from 34 weeks in those receiving vehicle to 20 weeks. A subset of 18 month old mice given alpha-lipoic acid for two weeks and then tested in an object-place recognition paradigm had improved memory. A second subset of 18 month old mice given alpha-lipoic acid for two weeks and tested in the Barnes maze had improved learning. After testing, the mice were sacrificed and indices of oxidative damage were measured in the brain tissue. The mice that received alpha-lipoic acid had significantly increased glutathione and decreased glutathione peroxidase and malondialdehyde indicating reversal of oxidative stress. These results indicate that alpha-lipoic acid improves memory and reverses indices of oxidative stress in extremely old SAMP8 mice, but decreases lifespan. These findings are similar to studies using other types of antioxidants. C1 [Farr, Susan A.] St Louis Univ, Sch Med, VA Med Ctr St Louis, Div Geriatr Med, St Louis, MO 63106 USA. [Farr, Susan A.] VA Med Ctr, Res & Dev Serv, St Louis, MO USA. [Price, Tulin O.; Morley, John E.] St Louis Univ, Sch Med, Div Endocrinol, St Louis, MO 63106 USA. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Ercal, Nuran] Missouri Univ Sci & Technol, Dept Chem, Rolla, MO USA. RP Farr, SA (reprint author), St Louis Univ, Sch Med, VA Med Ctr St Louis, Div Geriatr Med, 915 N Grand Blvd,151-JC, St Louis, MO 63106 USA. EM farrsa@slu.edu FU VA Medical Center, St. Louis, MO FX This work was supported by VA Medical Center, St. Louis, MO. NR 59 TC 20 Z9 21 U1 2 U2 12 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 32 IS 2 BP 447 EP 455 DI 10.3233/JAD-2012-120130 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 022QY UT WOS:000309977800017 PM 22785389 ER PT J AU Royall, DR Palmer, RF Vidoni, ED Honea, RA Burns, JM AF Royall, Donald R. Palmer, Raymond F. Vidoni, Eric D. Honea, Robyn A. Burns, Jeffrey M. TI The Default Mode Network and Related Right Hemisphere Structures may be the Key Substrates of Dementia SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aging; cognition; dementia; g; functional status ID MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; CLINICAL DEMENTIA; CARDIORESPIRATORY FITNESS; HIPPOCAMPAL VOLUME; MISSING DATA; HUMAN BRAIN; MATTER LOSS; CONNECTIVITY; ATROPHY AB We have employed structural equation models to explicitly distinguish dementia-relevant variance in cognitive task performance (i.e., delta) from the variance that is unrelated to a dementing process (i.e., g'). Together g' and d comprise Spearman's "g". Although d represents only a minor fraction of the total variance in cognitive task performance, it is more strongly associated with dementia severity than is g'. In this analysis, we replicate delta in a new dataspace, the University of Kansas Brain Aging Project, and associate it specifically with regional grey matter atrophy by voxel-based morphometry of magnetic resonance imaging data. The latent variable d localizes to elements of the default mode network and related structures in the R hemisphere. C1 [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Royall, Donald R.; Palmer, Raymond F.; Vidoni, Eric D.; Honea, Robyn A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Royall, Donald R.] S Texas Vet Hlth Syst, Audie L Murphy Div, GRECC, San Antonio, TX USA. [Burns, Jeffrey M.] Univ Kansas, Med Ctr, KU Alzheimer & Memory Program, Dept Neurol, Kansas City, KS 66103 USA. RP Royall, DR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. EM royall@uthscsa.edu FU Julia and Van Buren Parr endowment for the study of Alzheimer's disease; National Institutes of Aging [R03AG026374, R21AG029615]; National Institute on Neurological Disorders and Stroke [K23NS058252]; University of Kansas General Clinical Research Center [M01RR023940]; University of Kansas Alzheimer's Disease Center [P30AG035982]; Heartland Institute for Clinical & Translational Research, University of Kansas Medical Center's CTSA [KL2 TR000119, UL1 TR00001]; [R01AG034614]; [R01AG033673]; [K01AG035042] FX This study was made possible by the Julia and Van Buren Parr endowment for the study of Alzheimer's disease. The sponsor had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The Brain Aging Project is supported by grants R03AG026374 and R21AG029615 from the National Institutes of Aging, grant K23NS058252 from the National Institute on Neurological Disorders and Stroke. The University of Kansas General Clinical Research Center (M01RR023940) provided essential space, expertise, and nursing support. Dr. Burns and Vidoni are supported by the University of Kansas Alzheimer's Disease Center (P30AG035982). Dr. Burns is also supported by R01AG034614 and R01AG033673. Dr. Vidoni is also supported by the Heartland Institute for Clinical & Translational Research, University of Kansas Medical Center's CTSA, KL2 TR000119 & UL1 TR00001. Dr. Honea is supported by K01AG035042. NR 65 TC 26 Z9 26 U1 1 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 32 IS 2 BP 467 EP 478 DI 10.3233/JAD-2012-120424 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 022QY UT WOS:000309977800019 PM 22842866 ER PT J AU Bianchi, MT Thomas, RJ Ellenbogen, JM AF Bianchi, Matt T. Thomas, Robert J. Ellenbogen, Jeffrey M. TI Hypnotics and Mortality Risk SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Editorial Material ID OBSTRUCTIVE SLEEP-APNEA C1 [Bianchi, Matt T.; Ellenbogen, Jeffrey M.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. [Bianchi, Matt T.; Thomas, Robert J.; Ellenbogen, Jeffrey M.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [Thomas, Robert J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Wang 720,55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org NR 6 TC 2 Z9 2 U1 0 U2 9 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2012 VL 8 IS 4 BP 351 EP 352 DI 10.5664/jcsm.2016 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 023TU UT WOS:000310059400001 PM 22893762 ER PT J AU Chen, ML Olson, HC Picciano, JF Starr, JR Owens, J AF Chen, Maida Lynn Olson, Heather Carmichael Picciano, Joseph F. Starr, Jacqueline R. Owens, Judith TI Sleep Problems in Children with Fetal Alcohol Spectrum Disorders SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE sleep disorders; fetal alcohol spectrum disorders; prenatal alcohol; pediatric insomnia; school-age children; fetal alcohol syndrome; maternal pregnancy drinking ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SCHOOL-AGED CHILDREN; PRENATAL ALCOHOL; EXPOSED INFANTS; YOUNG-CHILDREN; APNEA SYNDROME; BEHAVIOR; ADENOTONSILLECTOMY; MANAGEMENT; OUTCOMES AB Study Objectives: Sleep problems in children with fetal alcohol spectrum disorders (FASD) are reportedly common but not well characterized. Objectives were to: (1) assess sleep concerns in children with FASD using a caregiver-report survey, the Children's Sleep Habits Questionnaire (CSHQ); (2) compare CSHQ results with those of previously reported community sample; and (3) describe pilot polysomnography findings in children with FASD. Methods: Children with FASD were recruited from a behavioral intervention study, and participating caregivers completed the CSHQ. CSHQ results were compared with the original data from a previously published community sample of similar age. Participants with FASD and elevated CSHQ scores were offered overnight polysomnography. Results: Thirty-three children with FASD (4.1-12.1 years) were enrolled; 85% of children with FASD scored above the clinical cutoff Total Score of 41, reflecting marked sleep disturbance. Elevated subdomain scores occurred primarily in areas concerning for pediatric insomnia. Those with comorbid ADHD had elevated CSHQ on additional subdomains with no difference in Total Scores. Compared with the community sample, children with FASD had higher Total Scores on the CSHQ (52 vs. 39, p < 0.001). Polysomnography, completed in 5 subjects, revealed mild sleep disordered breathing and fragmented sleep with elevated non-respiratory arousal indices. Conclusions: Clinically significant sleep problems are present in children with FASD on both subjective and objective measures. Further investigation is needed to better describe these sleep disturbances and their impact on overall health and daytime neurobehavioral problems in this clinical population. C1 [Chen, Maida Lynn; Picciano, Joseph F.] Seattle Childrens Hosp, Res Inst, Ctr Child Hlth Dev & Behav, Seattle, WA 98105 USA. [Chen, Maida Lynn] Univ Washington, Sch Med, Dept Pediat, Div Pulm & Sleep Med, Seattle, WA 98195 USA. [Olson, Heather Carmichael] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Div Child Psychiat,Seattle Childrens Hosp,Res Ins, Seattle, WA 98195 USA. [Starr, Jacqueline R.] Forsyth Inst, Cambridge, MA USA. [Starr, Jacqueline R.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Owens, Judith] Childrens Natl Med Ctr, Div Pulm & Sleep Med, Washington, DC 20010 USA. RP Chen, ML (reprint author), Seattle Childrens Hosp, Res Inst, Ctr Child Hlth Dev & Behav, 4800 Sand Point Way NE,MS A-5937, Seattle, WA 98105 USA. EM maida.chen@seattlechildrens.org OI Starr, Jacqueline/0000-0002-3039-2311 FU Seattle Children's Research Institute Center for Clinical and Translational Research Mentored Scholar Program; U.S. Centers for Disease Control and Prevention [U01-0000DD038-05]; Seattle Children's Research Institute FX The authors express deep appreciation to the participating families and dedicated clinical and research team of the Washington State Fetal Alcohol Syndrome Diagnostic and Prevention Network (FAS DPN), led by Susan J. Astley, Ph.D. The FAS DPN is the source of participants for this research project. Without the generous participation of families, and the unwavering efforts of the team to better serve individuals with FASD, this research would not have been possible. Work related to this study was performed at Seattle Children's Hospital and Seattle Children's Research Institute. Support for this study provided by Seattle Children's Research Institute Center for Clinical and Translational Research Mentored Scholar Program; U.S. Centers for Disease Control and Prevention, Grant number U01-0000DD038-05; and Seattle Children's Research Institute. NR 40 TC 11 Z9 11 U1 2 U2 13 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2012 VL 8 IS 4 BP 421 EP 429 DI 10.5664/jcsm.2038 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 023TU UT WOS:000310059400012 PM 22893773 ER PT J AU Bianchi, MT Wang, W Klerman, EB AF Bianchi, Matt T. Wang, Wei Klerman, Elizabeth B. TI Sleep Misperception in Healthy Adults: Implications for Insomnia Diagnosis SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Insomnia; subjective sleep estimation; time perception; time cues ID STATE MISPERCEPTION; TIME-ESTIMATION; PERCEPTIONS; SUFFERERS; MEMORY AB Study Objectives: Time estimation is a complex cognitive task that is especially challenging when the time period includes sleep. To determine the accuracy of sleep duration perception, we investigated 44 healthy subjects participating in multi-day inpatient sleep protocols during which they had extended nighttime and short daytime sleep opportunities but no time cues or knowledge of time of day. Methods: The first sleep opportunity was at habitual sleep time and duration. The subsequent 3, 4, or 11 days had 12-h nighttime sleep opportunities and 4-h daytime nap opportunities, potentially creating an experimentally induced "insomnia" with substantial time awake during scheduled sleep. Results: Subjective sleep duration estimates were accurate for the first (habitual) sleep opportunity. The subjective reports following nighttime 12-h sleep opportunities significantly underestimated objective sleep duration, while those following daytime 4-h sleep opportunities significantly overestimated objective sleep duration. Misperception errors were not explained by poor sleep efficiency, which was lower during 4-h (similar to 39%) than 12-h opportunities (similar to 71%). Subjective sleep estimates after 4-h opportunities correlated with the percentage of REM and N3 sleep. Subjective sleep estimates following 12-h opportunities were, unexpectedly, negatively correlated with NREM stage 2 sleep. Conclusion: The estimation of sleep duration in the absence of time cues may depend on length of sleep opportunity and/or time of day. The results have implications for understanding sleep state misperception, which is an important consideration in patients with insomnia. C1 [Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. [Bianchi, Matt T.; Wang, Wei; Klerman, Elizabeth B.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Bianchi, Matt T.; Wang, Wei; Klerman, Elizabeth B.] Harvard Univ, Sch Med, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Sleep Div, 55 Fruit St,Wing 720, Boston, MA 02114 USA. EM mtbianchi@partners.org FU Department of Neurology, Massachusetts General Hospital; Center for Integration of Medicine and Innovative Technology; Clinical Investigator Training Program: Harvard/MIT Health Sciences and Technology - Beth Israel Deaconess Medical Center; NIH [P01-AG009975, RC2-HL101340, K02-HD045459, K24-HL105664]; NSBRI [HFP01603]; Respironics Corporation; Sony Corporation; [NCRR-GCRC-M01-RR02635] FX The authors thank Drs. Andrew Phillips and Catherine Chu-Shore for valuable discussions. Funding: Department of Neurology, Massachusetts General Hospital, Center for Integration of Medicine and Innovative Technology, and the Clinical Investigator Training Program: Harvard/MIT Health Sciences and Technology - Beth Israel Deaconess Medical Center, in collaboration with Pfizer, Inc. and Merck & Co. (MTB); NIH P01-AG009975, NSBRI HFP01603, NIH RC2-HL101340, K02-HD045459, and NIH K24-HL105664 (EBK); and NCRR-GCRC-M01-RR02635 to the BWH GCRC.; This was not an industry supported study. Dr. Bianchi has a patent pending on a home sleep monitoring device that may be used in the future for insomnia patients. Dr. Klerman has received support from Respironics and Sony Corporations. The other author has indicated no financial conflicts of interest. NR 26 TC 12 Z9 14 U1 0 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2012 VL 8 IS 5 BP 547 EP + DI 10.5664/jcsm.2154 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 023UC UT WOS:000310060400013 PM 23066367 ER PT J AU Montesi, SB Edwards, BA Malhotra, A Bakker, JP AF Montesi, Sydney B. Edwards, Bradley A. Malhotra, Atul Bakker, Jessie P. TI The Effect of Continuous Positive Airway Pressure Treatment on Blood Pressure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Review DE Systematic review; meta-analysis; obstructive sleep apnea; positive airway pressure; hypertension; blood pressure; lung ID OBSTRUCTIVE SLEEP-APNEA; PLACEBO-CONTROLLED TRIAL; HYPOPNEA SYNDROME; CPAP; HYPERTENSION; THERAPY; IMPACT; HEALTH; OXYGEN; MALES AB Study Objectives: We sought to provide an updated systematic review and meta-analysis of studies investigating the effect of positive airway pressure (PAP) treatment for obstructive sleep apnea (OSA) on systolic and diastolic blood pressure (SBP, DBP). Methods: Two independent investigators undertook a systematic search of the PubMed database (1980-2012) to identify randomized controlled trials comparing therapeutic PAP to sham-PAP, pill placebo, or standard care over at least one week in adult OSA patients without major comorbidities. The mean, variance, and sample size for diurnal and nocturnal SBP and DBP data were also extracted independently from each study. Random effects meta-analyses were conducted, followed by pre-specified subgroup and meta-regression analyses. Results: 32 studies were identified, with data available from 28 studies representing n = 1,948 patients. The weighted mean difference in diurnal SBP (-2.58 mm Hg, 95% CI -3.57 to -1.59 mm Hg) and DBP (-2.01 mm Hg, 95% CI -2.84 to -1.18 mm Hg) both significantly favored PAP treatment over control arms, with similar results seen in nocturnal readings. Statistically significant reductions in BP were seen in studies whose patients were younger, sleepier, had more severe OSA, and exhibited greater PAP adherence. Meta-regression indicated that the reductions in DBP with PAP were predicted by mean baseline BP (beta = -0.22, p = 0.02) and Epworth Sleepiness Scale scores (beta = -0.27, p = 0.04). Conclusions: PAP treatment for OSA is associated with modest but significant reductions in diurnal and nocturnal SBP and DBP. Future research should be directed towards identifying subgroups likely to reap greater treatment benefits as well as other therapeutic benefits provided by PAP therapy. C1 [Montesi, Sydney B.; Edwards, Bradley A.; Malhotra, Atul; Bakker, Jessie P.] Brigham & Womens Hosp, Sleep Disorders Res Program, Boston, MA 02115 USA. [Montesi, Sydney B.; Edwards, Bradley A.; Malhotra, Atul; Bakker, Jessie P.] Harvard Univ, Sch Med, Boston, MA USA. [Montesi, Sydney B.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Bakker, JP (reprint author), Brigham & Womens Hosp, Sleep Disorders Res Program, 221 Longwood Ave 036BLI, Boston, MA 02115 USA. EM jpbakker@partners.org FU National Health and Medical Research Council of Australia [1035115]; NIH [5R01HL085188-04, 5R01HL090897-03, 5K24HL093218-03, 1P01HL095491-01A1]; AHA [0840159N]; Philips Respironics FX The authors thank Drs. Dimsdale, Drager, Lloberes, Lozano, Oliveira, Poyares, Sharma, and Tomfohr for their help in providing missing data for these analyses. Dr. Edwards is supported by the National Health and Medical Research Council of Australia's CJ Martin Overseas Biomedical Fellowship (1035115). Dr. Malhotra is supported by NIH (5R01HL085188-04, 5R01HL090897-03, 5K24HL093218-03, 1P01HL095491-01A1) and AHA (0840159N) grants. No financial support was obtained for this investigation. All work performed at Sleep Disorders Research Program, Brigham & Women's Hospital & Harvard Medical School, Boston MA.; This was not an industry supported study. Dr. Malhotra is a consultant for Philips Respironics, SHC, SGS, Apnicure, Apnex, and Pfizer. Dr. Bakker has received funding from Philips Respironics. The other authors have indicated no financial conflicts of interest. NR 40 TC 81 Z9 87 U1 1 U2 13 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2012 VL 8 IS 5 BP 587 EP 596 DI 10.5664/jcsm.2170 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 023UC UT WOS:000310060400021 PM 23066375 ER PT J AU Berry, RB Budhiraja, R Gottlieb, DJ Gozal, D Iber, C Kapur, VK Marcus, CL Mehra, R Parthasarathy, S Quan, SF Redline, S Strohl, KP Ward, SLD Tangredi, MM AF Berry, Richard B. Budhiraja, Rohit Gottlieb, Daniel J. Gozal, David Iber, Conrad Kapur, Vishesh K. Marcus, Carole L. Mehra, Reena Parthasarathy, Sairam Quan, Stuart F. Redline, Susan Strohl, Kingman P. Ward, Sally L. Davidson Tangredi, Michelle M. TI Rules for Scoring Respiratory Events in Sleep: Update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE AASM Manual for the Scoring of Sleep and Associated Events; scoring respiratory events in sleep; sleep apnea definitions; apnea and hypopnea; respiratory effort related arousals; hypoventilation; Cheyne-Stokes breathing ID POSITIVE AIRWAY PRESSURE; CHEYNE-STOKES RESPIRATION; EXCESSIVE DAYTIME SLEEPINESS; INSPIRATORY FLOW LIMITATION; HEART-FAILURE PATIENTS; CARBON-DIOXIDE; NASAL CANNULA; INDUCTIVE PLETHYSMOGRAPHY; APNEA-HYPOPNEA; NONINVASIVE VENTILATION AB The American Academy of Sleep Medicine (AASM) Sleep Apnea Definitions Task Force reviewed the current rules for scoring respiratory events in the 2007 AASM Manual for the Scoring and Sleep and Associated Events to determine if revision was indicated. The goals of the task force were (1) to clarify and simplify the current scoring rules, (2) to review evidence for new monitoring technologies relevant to the scoring rules, and (3) to strive for greater concordance between adult and pediatric rules. The task force reviewed the evidence cited by the AASM systematic review of the reliability and validity of scoring respiratory events published in 2007 and relevant studies that have appeared in the literature since that publication. Given the limitations of the published evidence, a consensus process was used to formulate the majority of the task force recommendations concerning revisions. The task force made recommendations concerning recommended and alternative sensors for the detection of apnea and hypopnea to be used during diagnostic and positive airway pressure (PAP) titration polysomnography. An alternative sensor is used if the recommended sensor fails or the signal is inaccurate. The PAP device flow signal is the recommended sensor for the detection of apnea, hypopnea, and respiratory effort related arousals (RERAs) during PAP titration studies. Appropriate filter settings for recording (display) of the nasal pressure signal to facilitate visualization of inspiratory flattening are also specified. The respiratory inductance plethysmography (RIP) signals to be used as alternative sensors for apnea and hypopnea detection are specified. The task force reached consensus on use of the same sensors for adult and pediatric patients except for the following: (1) the end-tidal PCO2 signal can be used as an alternative sensor for apnea detection in children only, and (2) polyvinylidene fluoride (PVDF) belts can be used to monitor respiratory effort (thoracoabdominal belts) and as an alternative sensor for detection of apnea and hypopnea (PVDFsum) only in adults. The task force recommends the following changes to the 2007 respiratory scoring rules. Apnea in adults is scored when there is a drop in the peak signal excursion by >= 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative apnea sensor, for >= 10 seconds. Hypopnea in adults is scored when the peak signal excursions drop by >= 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for >= 10 seconds in association with either >= 3% arterial oxygen desaturation or an arousal. Scoring a hypopnea as either obstructive or central is now listed as optional, and the recommended scoring rules are presented. In children an apnea is scored when peak signal excursions drop by >= 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative sensor; and the event meets duration and respiratory effort criteria for an obstructive, mixed, or central apnea. A central apnea is scored in children when the event meets criteria for an apnea, there is an absence of inspiratory effort throughout the event, and at least one of the following is met: (1) the event is >= 20 seconds in duration, (2) the event is associated with an arousal or >= 3% oxygen desaturation, (3) (infants under 1 year of age only) the event is associated with a decrease in heart rate to less than 50 beats per minute for at least 5 seconds or less than 60 beats per minute for 15 seconds. A hypopnea is scored in children when the peak signal excursions drop is >= 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for >= the duration of 2 breaths in association with either >= 3% oxygen desaturation or an arousal. In children and adults, surrogates of the arterial PCO2 are the end-tidal PCO2 or transcutaneous PCO2 (diagnostic study) or transcutaneous PCO2 (titration study). For adults, sleep hypoventilation is scored when the arterial PCO2 (or surrogate) is > 55 mm Hg for >= 10 minutes or there is an increase in the arterial PCO2 (or surrogate) >= 10 mm Hg (in comparison to an awake supine value) to a value exceeding 50 mm Hg for >= 10 minutes. For pediatric patients hypoventilation is scored when the arterial PCO2 (or surrogate) is > 50 mm Hg for > 25% of total sleep time. In adults Cheyne-Stokes breathing is scored when both of the following are met: (1) there are episodes of >= 3 consecutive central apneas and/or central hypopneas separated by a crescendo and decrescendo change in breathing amplitude with a cycle length of at least 40 seconds (typically 45 to 90 seconds), and (2) there are five or more central apneas and/or central hypopneas per hour associated with the crescendo/decrescendo breathing pattern recorded over a minimum of 2 hours of monitoring. C1 [Berry, Richard B.] Univ Florida, Hlth Sci Ctr, Div Pulm Med, Gainesville, FL 32610 USA. [Budhiraja, Rohit] So Arizona VA Healthcare Syst, Tucson, AZ USA. [Gottlieb, Daniel J.] VA Boston Healthcare Syst, Boston, MA USA. [Gozal, David] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Iber, Conrad] Univ Minnesota, Minneapolis, MN USA. [Kapur, Vishesh K.] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Marcus, Carole L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Mehra, Reena; Strohl, Kingman P.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Parthasarathy, Sairam] Univ Arizona, Tucson, AZ USA. [Redline, Susan] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Redline, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Ward, Sally L. Davidson] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Pediat Pulmonol, Los Angeles, CA 90033 USA. [Tangredi, Michelle M.] American Acad Sleep Med, Darien, IL USA. RP Berry, RB (reprint author), Univ Florida, Hlth Sci Ctr, Div Pulm Med, POB 100225, Gainesville, FL 32610 USA. EM richard.berry@medicine.ufl.edu RI Parthasarathy, Sairam/L-1612-2013; Kapur, Vishesh/K-1054-2014; OI Kapur, Vishesh/0000-0002-5417-1097; Mehra, Reena/0000-0002-6222-2675 FU Board of Directors of the AASM; Dymedix, Inc. FX The task force thanks Christine Stepanski, MS, and Richard Rosenberg, PhD, for their valuable assistance during the consensus process and the Board of Directors of the AASM for their guidance and support. The task force also thanks Drs. Berry and Marcus for supplying the figures.; This was not an industry supported study. Drs. Berry and Redline have received a research grant from Dymedix, Inc. The other authors have indicated no financial conflicts of interest. NR 114 TC 552 Z9 574 U1 9 U2 62 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2012 VL 8 IS 5 BP 597 EP 619 DI 10.5664/jcsm.2172 PG 23 WC Clinical Neurology SC Neurosciences & Neurology GA 023UC UT WOS:000310060400022 PM 23066376 ER PT J AU Slavin-Mulford, J Sinclair, SJ Stein, M Malone, J Bello, I Blais, MA AF Slavin-Mulford, Jenelle Sinclair, Samuel Justin Stein, Michelle Malone, Johanna Bello, Iruma Blais, Mark A. TI External Validity of the Personality Assessment Inventory (PAI) in a Clinical Sample SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID DISCIPLINARY ADJUSTMENT; PSYCHIATRIC-INPATIENTS; CONCURRENT VALIDITY; CONSTRUCT-VALIDITY; COLLEGE-STUDENTS; MARITAL-STATUS; RC SCALES; MMPI-2; ALCOHOL; SUICIDE AB This study contributes to the ongoing construct validation of the Personality Assessment Inventory (PAI; Morey, 1991, 2007) by identifying nontest life-event correlates of the PAI full scales and subscales in a sample of psychiatric patients. The life-event data used in this study included education, marital status, and employment, as well as a history of suicide attempts, psychiatric hospitalizations, trauma, medical problems, hallucinations, paranoid ideation, drug abuse, alcohol abuse, and arrest. Correlations were calculated to explore the convergent and discriminant validity of the PAI scales relative to the life-event data. The results showed that the majority of the PAI scales (11 of 13) had meaningful correlations with at least 1 life-event variable. The PAI BOR scale had the greatest number of correlations and was associated with 8 life-event variables. In contrast, the PAI ANX and MAN scales had no correlations above a predetermined threshold (r >=.21). These findings add to the growing body of empirical correlates of the PAI and generally provide support for the construct validity of the PAI scales. C1 [Slavin-Mulford, Jenelle; Sinclair, Samuel Justin; Stein, Michelle; Malone, Johanna; Blais, Mark A.] Massachusetts Gen Hosp, PEaRL, Boston, MA 02114 USA. [Slavin-Mulford, Jenelle; Sinclair, Samuel Justin; Stein, Michelle; Malone, Johanna; Blais, Mark A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bello, Iruma] NYU, Dept Psychiat, Langone Med Ctr, New York, NY 10003 USA. RP Slavin-Mulford, J (reprint author), Massachusetts Gen Hosp, PEaRL, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM jenelle.slavin@gmail.com NR 56 TC 11 Z9 11 U1 0 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PY 2012 VL 94 IS 6 BP 593 EP 600 DI 10.1080/00223891.2012.681817 PG 8 WC Psychology, Clinical; Psychology, Social SC Psychology GA 024UC UT WOS:000310133400005 PM 22571412 ER PT J AU Siefert, CJ Stein, M Sinclair, SJ Antonius, D Shiva, A Blais, MA AF Siefert, Caleb J. Stein, Michelle Sinclair, Samuel Justin Antonius, Daniel Shiva, Andrew Blais, Mark A. TI Development and Initial Validation of a Scale for Detecting Inconsistent Responding on the Personality Assessment Inventory-Short Form SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID EFFICIENCY; PATTERNS; MMPI-2; PAI AB The goal of this investigation was the development of an Inconsistency scale (ICN-SF) for the Personality Assessment Inventory-Short Form (PAI-SF). In Study 1, 503 inpatient profiles were randomly assigned to a derivation or cross-validation sample. Ten correlated item pairs were identified using the derivation sample and placed on the ICN-SF. Psychometric properties of the ICN-SF total scores were comparable in the derivation and cross-validation samples. Total ICN-SF scores in both samples were significantly lower than scores obtained from computer-generated random samples. Diagnostic efficiency statistics are reported using multiple cut-off scores at various base rate estimates. ICN-SF scores greater than 8 reasonably balanced sensitivity and specificity rates. This cutoff correctly classified 92% of the random protocols and inaccurately classified 9% of the patient protocols in Study 1. In Study 2, PAI-SF scores from 627 forensic and civil inpatients produced similar results, effectively identifying cases with elevated scores on the full-form Inconsistency scale. Overall the results of both studies suggest that the ICN-SF can aid examiners in assessing for inconsistent responding. C1 [Siefert, Caleb J.] Univ Michigan, Dept Behav Sci, Dearborn, MI 48128 USA. [Stein, Michelle; Sinclair, Samuel Justin; Blais, Mark A.] Massachusetts Gen Hosp, PEaRL, Boston, MA 02114 USA. [Stein, Michelle; Sinclair, Samuel Justin; Blais, Mark A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Antonius, Daniel] SUNY Buffalo, Dept Psychiat, Buffalo, NY 14260 USA. [Antonius, Daniel; Shiva, Andrew] NYU, Sch Med, Dept Psychiat, New York, NY 10003 USA. [Shiva, Andrew] CUNY John Jay Coll Criminal Justice, Dept Psychol, New York, NY USA. RP Siefert, CJ (reprint author), Univ Michigan, Dept Behav Sci, CASL Bldg,4th Floor,Rm 4012,4901 Evergreen Rd, Dearborn, MI 48128 USA. EM csiefert@umd.umich.edu OI Shiva, Andrew/0000-0001-5069-239X NR 18 TC 2 Z9 2 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PY 2012 VL 94 IS 6 BP 601 EP 606 DI 10.1080/00223891.2012.684117 PG 6 WC Psychology, Clinical; Psychology, Social SC Psychology GA 024UC UT WOS:000310133400006 PM 22574923 ER PT J AU Wortzel, HS Blatchford, P Conner, L Adler, LE Binswanger, IA AF Wortzel, Hal S. Blatchford, Patrick Conner, Latoya Adler, Lawrence E. Binswanger, Ingrid A. TI Risk of Death for Veterans on Release From Prison SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID CORONARY-ARTERY-DISEASE; DEPRESSION; SUICIDE; ANXIETY; MEN; MORTALITY; COHORT; MODEL AB We sought to determine, among veterans released from Washington state prisons from 1999 through 2003, the risk of death from all causes, whether those veterans have faced a higher risk of death than have nonveterans, and whether having VA benefits decreased the risk of death. We linked data from a retrospective cohort study to data from the Veterans Benefit Administration. Mortality rates were compared between veteran and nonveteran former inmates. The crude rate of veteran mortality was 1,195 per 100,000 person-years, significantly higher than that of nonveterans (p<.001), but adjustment for demographic factors demonstrated no significant increased risk. VA benefits were associated with a reduced risk for all-cause deaths (hazard ratio, .376; 95% confidence interval, 0.18-0.79). Veterans share the heightened risk of death after release from prison faced by all released inmates and should be included in efforts to reduce the risks associated with transitioning from prison to the community. VA benefits appear to offer a protective effect, particularly against medical deaths. C1 [Wortzel, Hal S.] Denver Vet Affairs Med Ctr, Vet Integrated Serv Network VISN Mental Illness R, Educ & Clin Ctr MIRECC, Denver, CO USA. [Wortzel, Hal S.] Univ Colorado, Sch Med, Dept Psychiat, Div Forens Psychiat, Aurora, CO USA. [Wortzel, Hal S.] Univ Colorado, Neurobehav Disorders Program, Aurora, CO USA. [Blatchford, Patrick] Colorado Sch Publ Hlth, Aurora, CO USA. [Wortzel, Hal S.; Conner, Latoya; Adler, Lawrence E.] Denver Vet Hosp, VISN MIRECC 19, Denver, CO 80209 USA. [Binswanger, Ingrid A.] Univ Colorado, Dept Med, Div Gen Internal Med, Aurora, CO USA. RP Wortzel, HS (reprint author), Denver Vet Hosp, VISN MIRECC 19, 1055 Clermont St, Denver, CO 80209 USA. EM hal.wortzel@ucdenver.edu FU AHRQ HHS [K12HS019464, K12 HS019464]; NIDA NIH HHS [1R21DA031041-01, R21 DA031041] NR 22 TC 6 Z9 6 U1 1 U2 8 PU AMER ACAD PSYCHIATRY & LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 1093-6793 J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 2012 VL 40 IS 3 BP 348 EP 354 PG 7 WC Law; Psychiatry SC Government & Law; Psychiatry GA 021QE UT WOS:000309899600006 PM 22960917 ER PT J AU Somers, RC Lanning, RM Snee, PT Greytak, AB Jain, RK Bawendi, MG Nocera, DG AF Somers, Rebecca C. Lanning, Ryan M. Snee, Preston T. Greytak, Andrew B. Jain, Rakesh K. Bawendi, Moungi G. Nocera, Daniel G. TI A nanocrystal-based ratiometric pH sensor for natural pH ranges SO CHEMICAL SCIENCE LA English DT Article ID RESONANCE ENERGY-TRANSFER; QUANTUM DOTS; IN-VIVO; CDSE NANOCRYSTALS; XANTHENE DYES; FLUORESCENCE; MICROSCOPY; DONORS; NANOPARTICLES; EXCITATION AB A ratiometric fluorescent pH sensor based on CdSe/CdZnS nanocrystal quantum dots (NCs) has been designed for biological pH ranges. The construct is formed from the conjugation of a pH dye (SNARF) to NCs coated with a poly(amido amine) (PAMAM) dendrimer. The sensor exhibits a well-resolved ratio response at pH values between 6 and 8 under linear or two-photon excitation, and in the presence of a 4% bovine serum albumin (BSA) solution. C1 [Somers, Rebecca C.; Snee, Preston T.; Greytak, Andrew B.; Bawendi, Moungi G.; Nocera, Daniel G.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Lanning, Ryan M.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. [Lanning, Ryan M.; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bawendi, MG (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jain@steele.mgh.harvard.edu; mgb@mit.edu; nocera@mit.edu OI Greytak, Andrew/0000-0001-8978-6457 FU U. S. National Cancer Institute [R01-CA126642]; ISN ARO [W911NF-07-D-0004] FX This research was supported by the U. S. National Cancer Institute grants R01-CA126642 and by the ISN ARO W911NF-07-D-0004. NR 44 TC 33 Z9 34 U1 6 U2 77 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2041-6520 J9 CHEM SCI JI Chem. Sci. PY 2012 VL 3 IS 10 BP 2980 EP 2985 DI 10.1039/c2sc20212c PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 996MU UT WOS:000308094100010 PM 26413260 ER PT J AU Do, S Salvaggio, K Gupta, S Kalra, M Ali, NU Pien, H AF Do, Synho Salvaggio, Kristen Gupta, Supriya Kalra, Mannudeep Ali, Nabeel U. Pien, Homer TI Automated Quantification of Pneumothorax in CT SO COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE LA English DT Article ID TRAUMATIC PNEUMOTHORAX; COMPUTED-TOMOGRAPHY; CHEST TRAUMA; PATIENT; SIZE AB An automated, computer-aided diagnosis (CAD) algorithm for the quantification of pneumothoraces from Multidetector Computed Tomography (MDCT) images has been developed. Algorithm performance was evaluated through comparison to manual segmentation by expert radiologists. A combination of two-dimensional and three-dimensional processing techniques was incorporated to reduce required processing time by two-thirds (as compared to similar techniques). Volumetric measurements on relative pneumothorax size were obtained and the overall performance of the automated method shows an average error of just below 1%. C1 [Do, Synho; Salvaggio, Kristen; Gupta, Supriya; Kalra, Mannudeep; Ali, Nabeel U.; Pien, Homer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ali, Nabeel U.] Albany Med Coll, Albany, NY 12208 USA. RP Do, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400B, Boston, MA 02114 USA. EM sdo@nmr.mgh.harvard.edu FU Defense Advanced Research Projects Agency [N66001-10-1-2133]; Philips Healthcare; Siemens Healthcare; GE Healthcare FX This work was supported in part by the Defense Advanced Research Projects Agency under Award no. N66001-10-1-2133. Any opinions, findings, conclusions, or recommendations expressed in this paper are those of the authors and do not necessarily reflect the views of DARPA. The authors do not have any financial disclosures pertinent to this study. Outside of the submitted work, H. Pien has received research funding from Philips Healthcare and Siemens Healthcare, both unrelated to this project; and, M. Kalra has received research funding from GE Healthcare, also not related to this project. NR 18 TC 1 Z9 1 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1748-670X J9 COMPUT MATH METHOD M JI Comput. Math. Method Med. PY 2012 AR 736320 DI 10.1155/2012/736320 PG 7 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 019SN UT WOS:000309759700001 ER PT J AU Johnson, B Duffin, M Murphy, M AF Johnson, Brian Duffin, Michael Murphy, Michael TI Quantifying a relationship between place-based learning and environmental quality SO ENVIRONMENTAL EDUCATION RESEARCH LA English DT Article DE place-based learning; environmental quality; air quality ID EDUCATION; POLLUTION AB The goal of this study was to investigate the degree to which school-based and nonformal education programs that focus on air quality (AQ) achieved measurable AQ improvements, and whether specific instructional methods were associated with those improvements. We completed a standardized telephone interview with representatives of 54 AQ education programs. Quantitative analysis of these interviews generated three key findings: (1) nearly half (46%) of the programs we studied reported evidence that AQ had actually improved over the course of their projects; (2) most (89%) of the programs we studied took some sort of action to improve AQ; and (3) programs reporting more place-based learning qualities and practices such as service-learning and community partnerships were more likely to report improvements in AQ (r = .40, p < .01). C1 [Johnson, Brian] Antioch Univ New England, Keene, NH USA. [Duffin, Michael] PEER Associates Inc, Swanzey, NH USA. [Murphy, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Murphy, Michael] Harvard Univ, Sch Med, Boston, MA USA. RP Johnson, B (reprint author), Antioch Univ New England, Keene, NH USA. EM bjohnson2@antioch.edu NR 27 TC 1 Z9 1 U1 0 U2 14 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1350-4622 J9 ENVIRON EDUC RES JI Environ. Educ. Res. PY 2012 VL 18 IS 5 BP 609 EP 624 DI 10.1080/13504622.2011.640748 PG 16 WC Education & Educational Research; Environmental Studies SC Education & Educational Research; Environmental Sciences & Ecology GA 017RE UT WOS:000309607500002 ER PT J AU Olawaiye, AB Godoy, HE Shahzad, MMK Rauh-Hain, JA Lele, SB Odunsi, K AF Olawaiye, A. B. Godoy, H. E. Shahzad, M. M. K. Rauh-Hain, J. A. Lele, S. B. Odunsi, K. TI Comparison of outcomes in patients treated with multi-agent regiments of cisplatin, adriamycin, and VP-16 versus carboplatin and paclitaxel for advanced and recurrent endometrial cancer SO EUROPEAN JOURNAL OF GYNAECOLOGICAL ONCOLOGY LA English DT Article DE Advanced endometrial carcinoma; Multi-agent chemotherapies; Adriamycin; Cisplatin; Etoposide ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; MEDROXYPROGESTERONE ACETATE; MEGESTROL-ACETATE; OVARIAN-CANCER; CARCINOMA; TAMOXIFEN; ETOPOSIDE AB Objective: The objective of this study was to compare the efficacy of two multi-agent chemotherapeutic regiments that were previously used at the Institution for treatment of advanced and recurrent endometrial cancer. Methods: A retrospective review of patients with Stage III, IV, and recurrent endometrial cancer who received adjuvant chemotherapy at Roswell Park Cancer Institute over a period of 21 years. Two patient groups were defined based on treatment received: cisplatin, adriamycin, and VP-16 with or without megace (PAV-M), or carboplatin and paclitaxel (CT). Results: Forty-two patients with advanced or recurrent endometrial cancer were included in this review based on regimen received. Median duration of follow up was 55 months. Treatment with PAV-M resulted in more dose modifications compared to CT group (42% vs 11%, respectively). There were no significant differences in disease-free survival or overall survival. Conclusions: PAV/PAV-M is active in patients with advanced or recurrent endometrial cancer. However, toxicity associated with this triplet regimen may limit clinical use. C1 [Godoy, H. E.; Lele, S. B.; Odunsi, K.] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Olawaiye, A. B.] Univ Pittsburgh, Magee Womens Hosp, UPMC, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Shahzad, M. M. K.] Univ Wisconsin, Dept Obstet & Gynecol, Madison, WI 53706 USA. [Rauh-Hain, J. A.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Odunsi, K.] Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. RP Lele, SB (reprint author), Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. EM shashi.lele@roswellpark.org FU NCI NIH HHS [T32 CA108456] NR 15 TC 1 Z9 1 U1 0 U2 1 PU I R O G CANADA, INC PI MONTREAL PA 4900 COTE ST-LUC, APT#212, MONTREAL, QUEBEC H3W 2H3, CANADA SN 0392-2936 J9 EUR J GYNAECOL ONCOL JI Eur. J. Gynaecol. Oncol. PY 2012 VL 33 IS 5 BP 477 EP 479 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 019KN UT WOS:000309738600007 PM 23185791 ER PT J AU Iosifescu, DV AF Iosifescu, Dan V. TI The relation between mood, cognition and psychosocial functioning in psychiatric disorders SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Depression; Cognition; Functioning; Bipolar disorder; Major depressive disorder; Schizophrenia ID MAJOR DEPRESSIVE DISORDER; BIPOLAR-II DISORDER; EUTHYMIC PATIENTS; UNIPOLAR DEPRESSION; NEUROPSYCHOLOGICAL DYSFUNCTION; 1ST-DEGREE RELATIVES; EXECUTIVE FUNCTION; SOCIAL COGNITION; SCHIZOPHRENIA; DEFICITS AB Impairments in cognitive performance and inability to function in everyday life situations are present, in various degrees, in many severe mental illnesses, including major depressive disorder, bipolar disorder, and schizophrenia. Persistent mood symptoms (e.g., depression and mania) are associated with functional deficits in major depression and bipolar disorder, but also in conditions where mood symptoms are not the primary markers of the illness, such as in schizophrenia. While mood symptoms impact cognitive performance, both mood symptoms and cognitive deficits have a significant - and to some extent independent - impact on psychosocial functioning in psychiatric patients. Improved control of mood symptoms may represent an important strategy leading to improved functional outcomes. However, cognitive impairment may be an important independent dimension of many psychiatric disorders and such symptoms should also be considered a potential target of treatments aiming to reduce functional deficits. (C) 2012 Published by Elsevier B.V. C1 [Iosifescu, Dan V.] Mt Sinai Sch Med, Mood & Anxiety Disorders Program, New York, NY 10029 USA. [Iosifescu, Dan V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Iosifescu, Dan V.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Iosifescu, DV (reprint author), Mt Sinai Sch Med, Mood & Anxiety Disorders Program, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. EM dan.iosifescu@mssm.edu FU NIMH [R01 MH 079157]; Servier; Aspect Medical Systems; Forest Laboratories; Janssen Pharmaceutica FX Dr. losifescu is supported by NIMH Grant R01 MH 079157. The supplement that this article appears in was produced with an educational grant from Servier; the article was written independently.; In the last two years Dr. losifescu has been a consultant for CNS Response, Inc. Lifetime, Dr. losifescu has received research support from Aspect Medical Systems, Forest Laboratories and Janssen Pharmaceutica, has been a consultant for Forest Laboratories, Gerson Lehrman Group and Pfizer, Inc and has been a speaker for Eli Lilly & Co., Forest Laboratories, Pfizer, Inc and Reed-Elsevier. NR 55 TC 16 Z9 16 U1 3 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PY 2012 VL 22 SU 3 BP S499 EP S504 DI 10.1016/j.euroneuro.2012.08.002 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 020AR UT WOS:000309781300006 PM 22959115 ER PT J AU Manier, S Sacco, A Leleu, X Ghobrial, IM Roccaro, AM AF Manier, S. Sacco, A. Leleu, X. Ghobrial, I. M. Roccaro, A. M. TI Bone Marrow Microenvironment in Multiple Myeloma Progression SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Review ID UNDETERMINED SIGNIFICANCE MGUS; MONOCLONAL GAMMOPATHY; METASTATIC NICHE; GROWTH-FACTOR; IN-VIVO; CELLS; INTERLEUKIN-6; DISEASE; ANGIOGENESIS; PATHOGENESIS AB Substantial advances have been made in understanding the biology of multiple myeloma (MM) through the study of the bone marrow (BM) microenvironment. Indeed, the BM niche appears to play an important role in differentiation, migration, proliferation, survival, and drug resistance of the malignant plasma cells. The BM niche is composed of a cellular compartment (stromal cells, osteoblasts, osteoclasts, endothelial cells, and immune cells) and a noncellular compartment including the extracellular matrix (ECM) and the liquid milieu (cytokines, growth factors, and chemokines). In this paper we discuss how the interaction between the malignant plasma cell and the BM microenvironment allowed myeloma progression through cell homing and the new concept of premetastatic niche. C1 [Manier, S.; Sacco, A.; Ghobrial, I. M.; Roccaro, A. M.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Manier, S.; Leleu, X.] CHRU Lille, Serv Malad Sang, F-59000 Lille, France. RP Roccaro, AM (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 450 Brookline Ave,HIM 246, Boston, MA 02215 USA. EM aldo_roccaro@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128 NR 46 TC 59 Z9 59 U1 0 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2012 AR 157496 DI 10.1155/2012/157496 PG 5 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 019SB UT WOS:000309758500001 ER PT J AU Saleh, MG Sharp, SK Alhamud, A Spottiswoode, BS van der Kouwe, AJW Davies, NH Franz, T Meintjes, EM AF Saleh, Muhammad G. Sharp, Sarah-Kate Alhamud, Alkathafi Spottiswoode, Bruce S. van der Kouwe, Andre J. W. Davies, Neil H. Franz, Thomas Meintjes, Ernesta M. TI Long-Term Left Ventricular Remodelling in Rat Model of Nonreperfused Myocardial Infarction: Sequential MR Imaging Using a 3T Clinical Scanner SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Article ID MAGNETIC-RESONANCE MICROSCOPY; LATE GADOLINIUM-ENHANCEMENT; CARDIAC-FUNCTION; HEART-FAILURE; EJECTION FRACTION; MOUSE HEART; CINE-MRI; MICE; MASS; SEGMENTATION AB Purpose. To evaluate whether 3T clinical MRI with a small-animal coil and gradient-echo (GE) sequence could be used to characterize long-termleft ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI) using semi-automatic segmentation software (SASS) in a rat model. Materials and Methods. 5 healthy rats were used to validate left ventricular mass (LVM) measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned at 2 and 4 weeks after surgery to allow for functional and structural analysis of the heart. Measurements included ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the heart were quantified using wall thickness analyses. Results. LVM validation in healthy rats demonstrated high correlation between MR and postmortem values. Functional assessment at 4 weeks after MI revealed considerable reduction in EF, increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE sequence generated images in a rat heart with adequate signal-to-noise ratio (SNR) for successful semiautomatic segmentation to accurately and rapidly evaluate long-term LVR after MI. C1 [Saleh, Muhammad G.; Alhamud, Alkathafi; Spottiswoode, Bruce S.; Meintjes, Ernesta M.] Univ Cape Town, MRC UCT Med Imaging Res Unit, Dept Human Biol, ZA-7925 Observatory, South Africa. [Sharp, Sarah-Kate; Davies, Neil H.; Franz, Thomas] Univ Cape Town, Chris Barnard Div Cardiothorac Surg, Cardiovasc Res Unit, ZA-7925 Observatory, South Africa. [Spottiswoode, Bruce S.] Univ Stellenbosch, Div Radiodiagnosis, ZA-7602 Matieland, South Africa. [van der Kouwe, Andre J. W.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [van der Kouwe, Andre J. W.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Franz, Thomas] Univ Cape Town, Ctr Res Computat & Appl Mech, ZA-7701 Rondebosch, South Africa. [Franz, Thomas] Ctr High Performance Comp, ZA-7700 Johannesburg, South Africa. RP Saleh, MG (reprint author), Univ Cape Town, MRC UCT Med Imaging Res Unit, Dept Human Biol, ZA-7925 Observatory, South Africa. EM mgsaleh7@gmail.com OI Sharp, Sarah-Kate/0000-0001-9947-3438; Franz, Thomas/0000-0002-1504-3842 FU South African Research Chairs Initiative of the Department of Science and Technology; National Research Foundation of South Africa; Medical Research Council of South Africa; NIH [R21AA017410] FX The authors would like to thank Fulufhelo Masithulela for assistance with handling of the animals, Dr. Vijay Dahya for advice and guidance on image segmentation, Charles Harris for construction of the rat bed, Mogammad Fakier for construction of the automatic temperature regulation system, and Dr. Lawrence Wald and Azma Mareyam from the Martinos Center for Biomedical Imaging at Massachusetts General Hospital for guidance in building the small animal coil. This study was supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa, the Medical Research Council of South Africa, and NIH Grant no. R21AA017410. NR 50 TC 4 Z9 4 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2012 AR 504037 DI 10.1155/2012/504037 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 019VW UT WOS:000309768700001 ER PT S AU Xu, Y Xu, C Price, BD AF Xu, Ye Xu, Chang Price, Brendan D. BE Doetsch, PW TI Mechanistic Links Between ATM and Histone Methylation Codes During DNA Repair SO MECHANISMS OF DNA REPAIR SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID DOUBLE-STRAND BREAKS; ACTIVATION IN-VIVO; DAMAGE-RESPONSE; ATAXIA-TELANGIECTASIA; ACETYLTRANSFERASE ACTIVITY; LYSINE METHYLATION; KINASE-ACTIVITY; IONIZING-RADIATION; PROTEIN-KINASE; S-PHASE AB The ataxia telangiectasia-mutated (ATM) protein kinase is the master regulator of the DNA double-strand break (DSB) repair pathway. The activation of ATM involves its recruitment to the DSB through interaction with the mre11-rad50-nbs1 complex, followed by the acetylation of ATM by the Tip60 acetyltransferase. This acetylation of ATM within its regulatory domain is essential for activating ATM's kinase activity. Further work has now revealed that Tip60 is activated through direct interaction between Tip60's chromodomain and histone H3 trimethylated on lysine 9 (H3K9me3). The loading of Tip60 onto the chromatin at DSBs therefore represents the primary mechanism for activation of Tip60's acetyltransferase activity in response to DNA damage. The ability of H3K9me3 at DSBs to regulate the activity of Tip60 and the subsequent activation of ATM emphasizes the crucial role played by chromatin architecture in regulating DSB repair. Further, histone methylation and chromatin structure are disrupted in human cancers, implying that altered chromatin structure in tumor cells may impact DSB repair, increasing genomic instability and contributing to the progression of cancer. C1 [Xu, Ye; Xu, Chang; Price, Brendan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genome Stabil & DNA Repair,Dept Radiat Oncol, Boston, MA 02115 USA. RP Xu, Y (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Genome Stabil & DNA Repair,Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA64585, CA93602, R01 CA064585] NR 148 TC 9 Z9 11 U1 1 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-387665-2 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2012 VL 110 BP 263 EP 288 DI 10.1016/B978-0-12-387665-2.00010-9 PG 26 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BBU38 UT WOS:000308198900010 PM 22749149 ER PT S AU Kowalski, RM Giumetti, GW Schroeder, AN Reese, HH AF Kowalski, Robin M. Giumetti, Gary W. Schroeder, Amber N. Reese, Heather H. BE Wankel, LA Wankel, C TI CYBER BULLYING AMONG COLLEGE STUDENTS: EVIDENCE FROM MULTIPLE DOMAINS OF COLLEGE LIFE SO MISBEHAVIOR ONLINE IN HIGHER EDUCATION SE Cutting-edge Technologies in Higher Education LA English DT Article; Book Chapter ID E-MAIL; COMMUNICATION; VICTIMIZATION; PERSONALITY; PERFORMANCE; EXPERIENCES; SCHOOLS; YOUTH AB Although media and research accounts of cyber bullying suggest this misbehavior is localized primarily among middle school students, and that its frequency decreases with age, this chapter presents empirical data showing that cyber bullying occurs with considerable frequency among college students across multiple domains of life, specifically school and work. In Study 1, 28 male and 82 female undergraduate students completed a survey examining their online activities as well as their experiences with cyber bullying. Over 30% of the participants indicated that their first experience with cyber bullying was in college. No gender differences were observed with regard to victimization or perpetration, except with online gaming where males reported a higher rate of victimization than females. With regard to personality differences among victims and perpetrators, victims were lower in agreeableness than non-victims. Study 2 examined the prevalence of cyber bullying among 107 college students at work, as well as the negative outcomes linked to the experience of workplace cyber bullying. Nearly a third of the college student sample reported having been the target of cyber bullying within the past six months. Individuals in jobs in which the Internet is essential and racial minorities reported higher rates of cyber bullying at work. Additionally, cyber bullying was positively linked to several negative emotions, as well as burnout and job search effort. These findings have important implications not only for potential negative outcomes that college students may be facing at school and at work but also for organizational justice issues, as differential treatment at work can lead to lawsuits and other negative work outcomes. C1 [Kowalski, Robin M.; Schroeder, Amber N.] Clemson Univ, Ind Org Psychol Program, Clemson, SC 29634 USA. [Reese, Heather H.] US Dept Vet Affairs, Columbia, SC USA. [Giumetti, Gary W.] Georgia Coll, Milledgeville, GA 31061 USA. RP Kowalski, RM (reprint author), Clemson Univ, Ind Org Psychol Program, Clemson, SC 29634 USA. NR 64 TC 14 Z9 14 U1 3 U2 7 PU EMERALD GROUP PUBLISHING LTD PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY, W YORKSHIRE BD16 1WA, ENGLAND SN 2044-9968 BN 978-1-78052-456-6 J9 CUT TECHNOL HIGH ED PY 2012 VL 5 BP 293 EP 321 DI 10.1108/S2044-9968(2012)0000005016 PG 29 WC Education & Educational Research SC Education & Educational Research GA BAJ29 UT WOS:000304329500014 ER PT S AU Neuringer, IP AF Neuringer, I. P. BE Atala, A TI Lung progenitor and stem cell biology and therapy SO PROGENITOR AND STEM CELL TECHNOLOGIES AND THERAPIES SE Woodhead Publishing Series in Biomaterials LA English DT Article; Book Chapter DE basal cell; Clara cell; bronchioalveolar stem cell (BASC); type I and type II alveolar cells; mesenchymal stem cell (MSC); endothelial progenitor stem cell (EPSC); COPD; ARDS ID MESENCHYMAL STROMAL CELLS; PULMONARY ARTERIAL-HYPERTENSION; ALVEOLAR EPITHELIAL-CELLS; SIDE POPULATION CELLS; BONE-MARROW; II CELLS; CYSTIC-FIBROSIS; BASAL-CELLS; IN-VIVO; ENDOTHELIAL PROGENITORS AB This chapter outlines the diverse populations of endogenous and circulating lung stem cells which play a role in lung homeostasis and responses to lung injury. The role of lung stem cells in the pathobiology of such lung diseases as COPD, lung cancer, ARDS, pulmonary fibrosis, pulmonary hypertension, and cystic fibrosis is discussed, as well as the potential benefit of lung stem cell therapy. Significant advances in the field include transgenic mouse models to test mechanisms of lung stem cell function, and bioengineered lung tissue. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Neuringer, IP (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM ineuringer@partners.org NR 153 TC 0 Z9 0 U1 0 U2 3 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2049-9485 BN 978-0-85709-607-4; 978-1-84569-984-0 J9 WOODH PUBL SER BIOM PY 2012 VL 38 BP 463 EP 500 D2 10.1533/9780857096074 PG 38 WC Cell & Tissue Engineering; Cell Biology; Engineering, Biomedical SC Cell Biology; Engineering GA BCI09 UT WOS:000310233400021 ER PT J AU Glidden, MD Celli, JP Massodi, I Rizvi, I Pogue, BW Hasan, T AF Glidden, Michael D. Celli, Jonathan P. Massodi, Iqbal Rizvi, Imran Pogue, Brian W. Hasan, Tayyaba TI Image-Based Quantification of Benzoporphyrin Derivative Uptake, Localization, and Photobleaching in 3D Tumor Models, for Optimization of PDT Parameters SO THERANOSTICS LA English DT Article DE Photodynamic therapy; PDT; photosensitizer imaging; fractionation; verteporfin; BPD; in vitro 3D tumor model ID RING-A BPD; PHOTODYNAMIC THERAPY; 5-AMINOLEVULINIC ACID; LIGHT FRACTIONATION; FLUENCE RATE; IN-VIVO; CANCER; PHOTOSENSITIZERS; ILLUMINATION; DOSIMETRY AB Photodynamic therapy (PDT) is a light-based treatment modality in which wavelength specific activation of a photosensitizer (PS) generates cytotoxic response in the irradiated region. PDT response is critically dependent on several parameters including light dose, PS dose, uptake time, fluence rate, and the mode of light delivery. While the systematic optimization of these treatment parameters can be complex, it also provides multiple avenues for enhancement of PDT efficacy under diverse treatment conditions, provided that a rational framework is established to quantify the impact of parameter selection upon treatment response. Here we present a theranostic technique, combining the inherent ability of the PS to serve simultaneously as a therapeutic and imaging agent, with the use of image-based treatment assessment in three dimensional (3D) in vitro tumor models, to comprise a platform to evaluate the impact of PDT parameters on treatment outcomes. We use this approach to visualize and quantify the uptake, localization, and photobleaching of the PS benzoporphyrin derivative monoacid ring-A (BPD) in a range of treatment conditions with varying uptake times as well as continuous and fractionated light delivery regimens in 3D cultures of AsPC-1 and PANC-1 cells. Informed by photobleaching patterns and correlation with cytotoxic response, asymmetric fractionated light delivery at 4 hours BPD uptake was found to be the most effective regimen assessed. Quantification of the spatial profile of cell killing within multicellular nodules revealed that these conditions also achieve the highest depth of cytotoxicity along the radial axis of 3D nodules. The framework introduced here provides a means for systematic assessment of PDT treatment parameters in biologically relevant 3D tumor models with potential for broader application to other systems. C1 [Glidden, Michael D.; Celli, Jonathan P.; Massodi, Iqbal; Rizvi, Imran; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Glidden, Michael D.; Celli, Jonathan P.] Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. [Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@partners.org OI Rizvi, Imran/0000-0001-9673-4700 FU National Institutes of Health [P01CA084203-06]; Harvard Medical School [K99CA155045-02] FX This work was supported by funding provided by the National Institutes of Health, though the Hasan Program Project Grant P01CA084203-06 (to T. H., B. W. P.) and a Howard Temin Pathway to Independence in Cancer Research Award K99CA155045-02 (to J.P.C.) and also a junior faculty career development award from the Eleanor and Miles Shore Scholars in Medicine Program at Harvard Medical School (to J.P.C.). NR 34 TC 22 Z9 22 U1 5 U2 22 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 9 BP 827 EP 839 DI 10.7150/thno.4334 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 021LH UT WOS:000309885800003 PM 23082096 ER PT J AU Royall, DR Palmer, RF AF Royall, Donald R. Palmer, Raymond F. TI Estimating the Temporal Evolution of Alzheimer's Disease Pathology with Autopsy Data SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; longitudinal; neuropathology; old age ID NEUROFIBRILLARY TANGLES; COGNITIVE IMPAIRMENT; SENILE PLAQUES; MISSING DATA; DEMENTIA; MODERATORS; MEDIATORS; SEVERITY; INDEXES; WORK AB The temporal growth of Alzheimer's disease (AD) neuropathology cannot be easily determined because autopsy data are available only after death. We combined autopsy data from 471 participants in the Honolulu-Asia Aging Study (HAAS) into latent factor measures of neurofibrillary tangle and neuritic plaque counts. These were associated with intercept and slope parameters from a latent growth curve (LGC) model of 9-year change in cognitive test performance in 3244 autopsied and non-autopsied HAAS participants. Change in cognition fully mediated the association between baseline cognitive performance and AD lesions counts. The mediation effect of cognitive change on both AD lesion models effectively dates them within the period of cognitive surveillance. Additional analyses could lead to an improved understanding of lesion propagation in AD. C1 [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78284 USA. [Royall, Donald R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78284 USA. [Royall, Donald R.; Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78284 USA. [Royall, Donald R.] S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, San Antonio, TX USA. RP Royall, DR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM royall@uthscsa.edu FU Julia and Van Buren Parr professorship in Aging and Geriatric Psychiatry; NINDS R21 [NS048123-01, N01-AG-4-2149]; National Institute on Aging [U01 AG019349] FX HAAS data were provided by Lon R. White (LRW), the HAAS Principal Investigator but HAAS staff were not further involved in the analysis or interpretation of the data. DRR and RFP were funded by the Julia and Van Buren Parr professorship in Aging and Geriatric Psychiatry. The authors accept full responsibility for all analyses, results and interpretations.; This work has been supported by NINDS R21 Grant NS048123-01, contract N01-AG-4-2149, and grant U01 AG019349 from the National Institute on Aging. Portions of this work were presented at the 2011 AAICAD, Paris, France. NR 29 TC 3 Z9 3 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 32 IS 1 BP 23 EP 32 DI 10.3233/JAD-2012-120430 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 016LA UT WOS:000309518600004 PM 22695618 ER PT J AU Wharton, W Stein, JH Korcarz, C Sachs, J Olson, SR Zetterberg, H Dowling, M Ye, SY Gleason, CE Underbakke, G Jacobson, LE Johnson, SC Sager, MA Asthana, S Carlsson, CM AF Wharton, Whitney Stein, James H. Korcarz, Claudia Sachs, Jane Olson, Sandra R. Zetterberg, Henrik Dowling, Maritza Ye, Shuyun Gleason, Carey E. Underbakke, Gail Jacobson, Laura E. Johnson, Sterling C. Sager, Mark A. Asthana, Sanjay Carlsson, Cynthia M. TI The Effects of Ramipril in Individuals at Risk for Alzheimer's Disease: Results of a Pilot Clinical Trial SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; angiotensin converting enzyme; antihypertensive; arterial function; blood pressure; clinical trial; cognition; hypertension; prevention; vascular risk ID ANGIOTENSIN-CONVERTING ENZYME; CEREBROSPINAL-FLUID; RECEPTOR BLOCKERS; COGNITIVE DECLINE; ACE-INHIBITORS; DEMENTIA; MEMORY; BRAIN; HYPERTENSION; PROGRESSION AB Research shows that certain antihypertensives taken during midlife confer Alzheimer's disease (AD) related benefits in later life. We conducted a clinical trial to evaluate the extent to which the angiotensin converting enzyme inhibitor (ACE-I), ramipril, affects AD biomarkers including cerebrospinal fluid (CSF) amyloid-beta (A beta) levels and ACE activity, arterial function, and cognition in participants with a parental history of AD. This four month randomized, double-blind, placebo-controlled, pilot clinical trial evaluated the effects of ramipril, a blood-brain-barrier crossing ACE-I, in cognitively healthy individuals with mild, or Stage I hypertension. Fourteen participants were stratified by gender and apolipoprotein E epsilon 4 (APOE epsilon 4) status and randomized to receive 5mg of ramipril or matching placebo daily. Participants were assessed at baseline and month 4 on measures of CSF A beta(1-42) and ACE activity, arterial function, and cognition. Participants were middle-aged (mean 54 y) and highly educated (mean 15.4 y), and included 50% men and 50% APOE epsilon 4 carriers. While results did not show a treatment effect on CSF A beta(1-42) (p = 0.836), data revealed that ramipril can inhibit CSF ACE activity (p = 0.009) and improve blood pressure, however, there were no differences between groups in arterial function or cognition. In this study, ramipril therapy inhibited CSF ACE activity and improved blood pressure, but did not influence CSF A beta(1-42). While larger trials are needed to confirm our CSF A beta results, it is possible that prior research reporting benefits of ACE-I during midlife may be attributed to alternative mechanisms including improvements in cerebral blood flow or the prevention of angiotensin II-mediated inhibition of acetylcholine. C1 [Wharton, Whitney; Stein, James H.; Korcarz, Claudia; Olson, Sandra R.; Dowling, Maritza; Gleason, Carey E.; Jacobson, Laura E.; Johnson, Sterling C.; Sager, Mark A.; Asthana, Sanjay; Carlsson, Cynthia M.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53705 USA. [Wharton, Whitney; Olson, Sandra R.; Dowling, Maritza; Ye, Shuyun; Gleason, Carey E.; Jacobson, Laura E.; Johnson, Sterling C.; Sager, Mark A.; Asthana, Sanjay; Carlsson, Cynthia M.] Univ Wisconsin, Alzheimers Dis Res Ctr, Madison, WI 53705 USA. [Wharton, Whitney; Olson, Sandra R.; Gleason, Carey E.; Jacobson, Laura E.; Johnson, Sterling C.; Asthana, Sanjay; Carlsson, Cynthia M.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Stein, James H.; Korcarz, Claudia; Sachs, Jane] Atherosclerosis Imaging Res Program, Div Cardiovasc Med, Madison, WI USA. Univ Wisconsin, Populat Hlth Inst, Madison, WI 53705 USA. [Zetterberg, Henrik] Univ Gothenburg, Dept Psychiat & Neurochem, Inst Neurosci & Physiol, Sahlgrenska Acad, Molndal, Sweden. [Dowling, Maritza; Ye, Shuyun] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53705 USA. [Underbakke, Gail] Univ Wisconsin, Prevent Cardiol Program, Madison, WI 53705 USA. [Sager, Mark A.; Asthana, Sanjay] Wisconsin Alzheimers Inst, Madison, WI USA. RP Wharton, W (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, William S Middleton Mem VA Hosp, 2500 Overlook Terrace,GRECC D4211, Madison, WI 53705 USA. EM wlwharto@medicine.wisc.edu FU State of Wisconsin; Wisconsin Alzheimer's Institute (WAI) [R01AG027161]; National Center for Research Resources of the NIH [1UL1RR025011] FX The study was supported by a grants from the State of Wisconsin and the Wisconsin Alzheimer's Institute (WAI) R01AG027161 and from the Clinical and Translational Science Award (CTSA) program of the National Center for Research Resources of the NIH 1UL1RR025011. We utilized the resources of the School of Medicine and Public Health at the University of Wisconsin (UW), the Wisconsin Alzheimer's Disease Research Center (UW ADRC) NIH P50 AG033514, UW Department of Medicine Division of Geriatrics and Gerontology, the Geriatric Research, Education and Clinical Center (GRECC) of the William S. Middleton Memorial Veterans Hospital, Madison WI and the UW Atherosclerosis Imaging Research Program. NR 53 TC 20 Z9 20 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 32 IS 1 BP 147 EP 156 DI 10.3233/JAD-2012-120763 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 016LA UT WOS:000309518600014 PM 22776970 ER PT J AU Moysidis, SN Thanos, A Vavvas, DG AF Moysidis, Stavros N. Thanos, Aristomenis Vavvas, Demetrios G. TI Mechanisms of Inflammation in Proliferative Vitreoretinopathy: From Bench to Bedside SO MEDIATORS OF INFLAMMATION LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; RHEGMATOGENOUS RETINAL-DETACHMENT; MASSIVE PERIRETINAL PROLIFERATION; RANDOMIZED CONTROLLED-TRIAL; MOLECULAR-WEIGHT HEPARIN; SOLUBLE TNF RECEPTORS; INTRAVITREAL INJECTION; EPIRETINAL MEMBRANES; EXPERIMENTAL-MODEL AB Proliferative vitreoretinopathy (PVR) is a vision-threatening disease and a common complication of surgery to correct rhegmatogenous retinal detachment (RRD). Several models of the pathogenesis of this disease have been described with some of these models focusing on the role of inflammatory cells and other models focusing on the role of growth factors and cytokines in the vitreous which come into contact with intraretinal and retinal pigment epithelial cells. New experiments have shed light on the pathogenesis of PVR and offer promising avenues for clinical intervention before PVR develops. One such target is the indirect pathway of activation of platelet-derived growth factor receptor alpha (PDGR alpha), which plays an important role in PVR. Clinical trials assessing the efficacy of 5-fluorouracil (5-FU) and low-molecular-weight heparin (LMWH), daunorubicin, and 13-cis-retinoic acid, among other therapies, have yielded mixed results. Here we review inflammatory and other mechanisms involved in the pathogenesis of PVR, we highlight important clinical trials, and we discuss how findings at the bench have the potential to be translated to the bedside. C1 [Moysidis, Stavros N.; Thanos, Aristomenis; Vavvas, Demetrios G.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. RP Vavvas, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM demetrios_vavvas@meei.harvard.edu OI Moysidis, Stavros/0000-0002-2639-8104; Vavvas, Demetrios/0000-0002-8622-6478 NR 82 TC 22 Z9 22 U1 1 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2012 AR 815937 DI 10.1155/2012/815937 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 016ZC UT WOS:000309557400001 ER PT J AU Dwivedi, N Radic, M AF Dwivedi, Nishant Radic, Marko TI Neutrophil activation and B-cell stimulation in the pathogenesis of Felty's syndrome SO POLSKIE ARCHIWUM MEDYCYNY WEWNETRZNEJ-POLISH ARCHIVES OF INTERNAL MEDICINE LA English DT Review DE autoantibodies; histone deimination; neutrophils; NETosis; systemic uatoimmunity ID GRANULAR LYMPHOCYTE LEUKEMIA; CYCLIC CITRULLINATED PEPTIDE; ANTI-DNA ANTIBODIES; RHEUMATOID-ARTHRITIS; IMMUNE-COMPLEXES; SUPEROXIDE GENERATION; AUTOANTIBODIES; ASSOCIATIONS; PROGRESSION; DEIMINATION AB Felty's syndrome (FS) is a severe arthritic disorder that features chronic neutrophil activation and progresses to neutropenia and susceptibility to unabated infections. The life-threatening manifestations of FS have focused the attention of clinical experimenters who have made persistent efforts to find new and effective therapies. This review highlights important milestones in the research on FS and draws attention to recent studies on the antigen specificity of antibodies present in patients' sera. Recent data have indicated that immunoglobulins G (IgGs) in patients with FS bind selectively and specifically to deiminated histones and neutrophil extracellular chromatin traps (NETs). Deimination is the conversion of certain arginine residues in proteins to citrullines by the enzyme peptidylarginine deiminase 4. Earlier observations had indicated that IgGs in FS patients avidly bind to citrullinated peptides. These observations suggest that NETosis, the type of cell death that is defined by the release of NETs, provides autoantigens that stimulate B cell responses in this patient group. This insight parallels recent observations in other autoimmune conditions and lends support to the paradigm that NETosis plays a leading role in the pathogenesis of antiself immune responses. C1 [Dwivedi, Nishant; Radic, Marko] Univ Tennessee, Hlth Sci Ctr, Dept Microbiol Immunol & Biochem, Memphis, TN 38163 USA. [Dwivedi, Nishant] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Dwivedi, Nishant] Childrens Hosp, Program Mol & Cellular Med, Boston, MA 02115 USA. [Dwivedi, Nishant] Harvard Univ, Sch Med, Boston, MA USA. RP Radic, M (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Microbiol Immunol & Biochem, 858 Madison Ave, Memphis, TN 38163 USA. EM mradic@uthsc.edu FU Lupus Research Institute of New York; Dana Foundation Program in Human Immunology FX The authors acknowledge the research support of the Lupus Research Institute of New York and the Dana Foundation Program in Human Immunology. NR 61 TC 4 Z9 5 U1 0 U2 1 PU MEDYCYNA PRAKTYCZNA PI KRAKOW PA UL KRAKOWSKA 41, KRAKOW, 31-066, POLAND SN 0032-3772 J9 POL ARCH MED WEWN JI Pol. Arch. Med. Wewn. PY 2012 VL 122 IS 7-8 BP 374 EP 378 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 016XK UT WOS:000309553000010 PM 22814518 ER PT J AU Kang, JX AF Kang, Jing X. TI The Coming of Age of Nutrigenetics and Nutrigenomics SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Editorial Material ID NUTRITION C1 [Kang, Jing X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, LLMT, 149-13th St,Room 4433, Charlestown, MA 02129 USA. EM kang.jing@mgh.harvard.edu NR 9 TC 1 Z9 1 U1 0 U2 12 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2012 VL 5 IS 1 BP I EP II DI 10.1159/000339375 PG 2 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 969YU UT WOS:000306096100001 ER PT J AU Hong, O Chin, DL Kerr, MJ Ronis, DL AF Hong, OiSaeng Chin, Dal Lae Kerr, Madeleine J. Ronis, David L. TI Stages of Change in Hearing-protection Behavior, Cognition, and Hearing Status SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE stages of change; hearing protection; cognitive perceptions; construction workers; hearing ability ID CONSTRUCTION WORKERS; NOISE EXPOSURE; INTERVENTION; PREVENTION; MOTIVATION; READINESS; STUDENTS; SMOKING; MODEL AB Objective: To determine stages of hearing-protection behavioral change and their relationships with cognitions and hearing status. Method: A cross-sectional study of 769 construction workers who completed a survey and audiometric tests. Results: The majority of participants (over 64%) were in the preparation stage. Participants in the action/maintenance stage demonstrated significantly greater benefits, self-efficacy, and interpersonal influence; fewer barriers; and better hearing. This is the first study that shows significantly better health outcome, hearing ability, as the stage progresses. Conclusion: Study demonstrates preliminary validity of the stages of change with hearing-protection behavior. Future hearing-protection intervention should integrate the stages of change to increase effectiveness. C1 [Hong, OiSaeng; Chin, Dal Lae] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Kerr, Madeleine J.] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [Ronis, David L.] Univ Michigan, Sch Nursing, US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI 48109 USA. RP Hong, O (reprint author), Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. EM oisaeng.hong@nursing.ucsf.edu FU NIOSH CDC HHS [5R01 OH04034-01A1] NR 41 TC 0 Z9 0 U1 0 U2 5 PU PNG PUBLICATIONS PI OAK RIDGE PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA SN 1945-7359 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PY 2012 VL 36 IS 6 BP 811 EP 822 DI 10.5993/AJHB.36.6.8 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 014EN UT WOS:000309358000008 PM 23026039 ER PT J AU Yu, MK Lyles, CR Bent-Shaw, LA Young, BA AF Yu, Margaret K. Lyles, Courtney Rees Bent-Shaw, Luis A. Young, Bessie A. CA Pathways Authors TI Risk Factor, Age and Sex Differences in Chronic Kidney Disease Prevalence in a Diabetic Cohort: The Pathways Study SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Sex difference; Gender difference; Diabetic kidney disease ID GLOMERULAR-FILTRATION-RATE; RENAL-DISEASE; PROGRESSION; GENDER; DISPARITIES; MICROALBUMINURIA; METAANALYSIS; MELLITUS; THERAPY; TYPE-1 AB Background/Aims: Women with diabetes experience a disproportionately greater burden of diabetic kidney disease (DKD) risk factors compared to men; however, sex-specific differences in DKD are not well defined. The effect of age on sex differences in DKD is unknown. Methods: We performed a cross-sectional analysis of the prevalence of DKD (eGFR <60 ml/min/1.73 m(2) or microalbuminuria), advanced DKD (eGFR <30 ml/min/1.73 m(2)), and common DKD risk factors in the Pathways Study (n = 4,839), a prospective cohort study of diabetic patients from a managed care setting. Subjects were stratified by age <60 and >= 60 years to examine for differences by age. Logistic regression models examined the association between sex and prevalence of DKD and risk factors. Results: Women of all ages had 28% decreased odds of DKD (OR 0.72,95% CI 0.62-0.83); however, they had a greater prevalence of advanced DKD (OR 1.67, 95% CI 1.05-2.64), dyslipidemia (OR 1.42,95% CI 1.16-1.74), and obesity (OR 1.87, 95% CI 1.60-2.20) compared to men. Women had similar odds of hypertension and poor glycemic control as men. Women >= 60 years had increased odds of advanced DKD, hypertension, dyslipidemia, and obesity compared to similarly aged men. Women <60 years had increased odds of obesity compared to their male counterparts. Conclusion: Women with diabetes had an increased prevalence of advanced DKD and common DKD risk factors compared to men and these disparities were most prominent amongst the elderly. Copyright (c) 2012 S. Karger AG, Basel C1 [Yu, Margaret K.; Bent-Shaw, Luis A.; Young, Bessie A.] Univ Washington, Div Nephrol, Seattle, WA 98108 USA. [Yu, Margaret K.; Young, Bessie A.] Univ Washington, Dept Epidemiol, Seattle, WA 98108 USA. [Lyles, Courtney Rees; Young, Bessie A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98108 USA. [Yu, Margaret K.; Bent-Shaw, Luis A.; Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Kidney Res Inst, Seattle, WA USA. [Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Young, BA (reprint author), Univ Washington, Div Nephrol, 1660 S Columbian Way,RDU 111A, Seattle, WA 98108 USA. EM youngb@u.washington.edu FU National Institutes of Health National Institute of Diabetes, Digestive, and Kidney Diseases [DK079745, T32 007467]; National Institute of Mental Health [MH41739, MH01643]; VA Puget Sound Health Care System, Seattle, Washington FX This work was supported by research grants by the National Institutes of Health National Institute of Diabetes, Digestive, and Kidney Diseases (DK079745, T32 007467) and National Institute of Mental Health (MH41739, MH01643). In addition, B.A.Y.'s contribution is supported by resources from the VA Puget Sound Health Care System, Seattle, Washington. NR 26 TC 6 Z9 6 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2012 VL 36 IS 3 BP 245 EP 251 DI 10.1159/000342210 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 014NW UT WOS:000309383800006 PM 22964976 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI The print in early modern England: An historical oversight SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PY 2012 VL 10 IS 2 BP 199 EP 201 DI 10.1080/17460654.2012.666128 PG 5 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA 013AI UT WOS:000309277500007 ER PT J AU Vasquez, DA de Arellano, MA Reid-Quinones, K Bridges, AJ Rheingold, AA AF Vasquez, Desi Alonzo de Arellano, Michael A. Reid-Quinones, Kathryn Bridges, Ana J. Rheingold, Alyssa A. TI Peritraumatic Dissociation and Peritraumatic Emotional Predictors of PTSD in Latino Youth: Results from the Hispanic Family Study SO JOURNAL OF TRAUMA & DISSOCIATION LA English DT Article DE peritraumatic dissociation; PTSD; Latino; youth; shame ID POSTTRAUMATIC-STRESS-DISORDER; TERRORIST ATTACKS; MENTAL-HEALTH; UNITED-STATES; SEXUAL-ABUSE; CHILDREN; SYMPTOMS; SHAME; ADOLESCENTS; VICTIMS AB This is the 1st study to examine peritraumatic dissociation and peritraumatic emotions as they predict symptoms and diagnosis of posttraumatic stress disorder (PTSD) in Latino youth. Our aim was to test the hypothesis that the degree of peritraumatic dissociation would predict the number of PTSD symptoms and PTSD clinical diagnosis when the influences of other salient factors were statistically controlled. We also explored the possible contributions of peritraumatic emotional responses to PTSD symptomatology and PTSD diagnosis. We expected that peritraumatic dissociation would emerge as a significant predictor of PTSD. A total of 204 Latino youth (mean age = 12.37 years) completed semistructured individual clinical interviews with bilingual research assistants. These interviews assessed trauma exposure, peritraumatic responses, and current psychopathology. A linear regression analysis demonstrated significant relationships between lifetime number of traumatic events, peritraumatic dissociation, shame, and number of PTSD symptoms endorsed. Significant inverse (protective) relationships were demonstrated between anger and guilt and current PTSD symptomatology. Logistic regression analysis demonstrated significant relationships between peritraumatic dissociation, shame, lifetime number of traumatic events experienced, and PTSD diagnosis. The analyses examined both the number of PTSD symptoms as well as diagnosis of PTSD while simultaneously controlling for age, lifetime exposure to traumatic events, time residing in the United States, and gender. These results support an increasingly robust body of empirical literature suggesting that the peritraumatic dissociative and emotional responses to trauma are important predictors of future PTSD diagnosis. Possible cultural factors contributing to the dissociative responses in Latino youth and clinical implications are discussed. C1 [Vasquez, Desi Alonzo; de Arellano, Michael A.; Reid-Quinones, Kathryn; Rheingold, Alyssa A.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Bridges, Ana J.] Univ Arkansas, Dept Psychol, Fayetteville, AR 72701 USA. RP Vasquez, DA (reprint author), S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd 116B, San Antonio, TX 78229 USA. EM Desi.Vasquez@va.gov OI Stocker, Ryan/0000-0001-9271-266X FU NIMH NIH HHS [K01 MH001815-01, K01 MH001815, T32 MH18869-23, T32 MH018869]; PHS HHS [D40HP19640] NR 47 TC 2 Z9 2 U1 3 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1529-9732 J9 J TRAUMA DISSOCIATIO JI J. Trauma Dissociation PY 2012 VL 13 IS 5 BP 509 EP 525 DI 10.1080/15299732.2012.678471 PG 17 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 008ST UT WOS:000308977600002 PM 22989240 ER PT J AU Kirby, AC Beckham, JC Calhoun, PS Roberts, ST Taft, CT Elbogen, EB Dennis, MF AF Kirby, Angela C. Beckham, Jean C. Calhoun, Patrick S. Roberts, Sushma T. Taft, Casey T. Elbogen, Eric B. Dennis, Michelle F. TI An Examination of General Aggression and Intimate Partner Violence in Women With Posttraumatic Stress Disorder SO VIOLENCE AND VICTIMS LA English DT Article DE posttraumatic stress disorder; violence; aggression; women ID NATIONAL COMORBIDITY SURVEY; MAJOR DEPRESSIVE DISORDER; FEMALE VIETNAM VETERANS; ADMINISTERED PTSD SCALE; COMBAT VETERANS; INTERPERSONAL VIOLENCE; MILITARY VETERANS; TRAUMATIC EVENTS; RISK-FACTORS; HOSTILITY AB Research has documented significant relationships between posttraumatic stress disorder (PTSD), aggression, and intimate partner violence (IPV). Most of these studies have focused on men and measured violence by self-report. This study examined (a) the association between PTSD and general aggression among women, (b) the association between IPV and PTSD among married and/or cohabitating couples, and (c) the concordance between self and collateral reports of IPV. One hundred twenty participants provided information about PTSD symptoms and general aggression toward others, and 43 married and/or cohabitating couples provided information about PTSD and IPV. Women with PTSD reported more general aggression, IPV perpetration, and IPV victimization. Collateral informants of those with and without PTSD did not differ significantly in their report of IPV. Concordance between participants and spouses or partners was low to moderate. These results are discussed within the context of extant IPV literature. C1 [Kirby, Angela C.] Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, Durham, NC 27705 USA. [Kirby, Angela C.; Beckham, Jean C.; Calhoun, Patrick S.; Elbogen, Eric B.] VA Midatlantic Reg Mental Illness Res Educ & Clin, Durham, NC USA. [Taft, Casey T.] Boston Univ, Sch Med, Natl Ctr PTSD, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Elbogen, Eric B.] Univ N Carolina, Chapel Hill, NC USA. [Dennis, Michelle F.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. RP Kirby, AC (reprint author), Vet Affairs Med Ctr, Mental Illness Res Educ & Clin Ctr, 508 Fulton St, Durham, NC 27705 USA. EM angela.kirby@va.gov FU NIMH NIH HHS [2R01MH62482, R01 MH062482] NR 61 TC 11 Z9 11 U1 4 U2 14 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, NEW YORK, NY 10036 USA SN 0886-6708 J9 VIOLENCE VICTIMS JI Violence Vict. PY 2012 VL 27 IS 5 BP 777 EP 792 DI 10.1891/0886-6708.27.5.777 PG 16 WC Criminology & Penology SC Criminology & Penology GA 007GV UT WOS:000308877700009 PM 23155726 ER PT J AU Casciano, JP Singer, DE Kwong, WJ Fox, ES Martin, BC AF Casciano, Julian P. Singer, Daniel E. Kwong, Winghan Jacqueline Fox, Eben S. Martin, Bradley C. TI Anticoagulation Therapy for Patients with Non-Valvular Atrial Fibrillation Comparison of Decision Analytic Model Recommendations and Real-World Warfarin Prescription Use SO AMERICAN JOURNAL OF CARDIOVASCULAR DRUGS LA English DT Article ID NET CLINICAL BENEFIT; STROKE PREVENTION; RISK-FACTORS; ANTITHROMBOTIC THERAPY; ORAL ANTICOAGULANTS; COST-EFFECTIVENESS; ISCHEMIC-STROKE; ASPIRIN; METAANALYSIS; PROPHYLAXIS AB Background: Anticoagulation in patients with atrial fibrillation (AF) is challenging because stroke-risk reduction must be balanced against increased bleeding risk. Objective: We developed a decision model integrating both stroke and bleeding risk schemes to guide optimal use of anticoagulation in AF, and compared model recommendations with warfarin use in a real-world database. Methods: A Markov model based on demographics, CHADS(2) (Congestive Heart Failure, Hypertension, Age of 75 years and greater, Diabetes Mellitus and History of Stroke) stroke and ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) bleed risk scores, and anticoagulation treatment effects from clinical trials simulated health state transitions for recently diagnosed AF patients. The model recommended the treatment with greater quality-adjusted life expectancy. Model recommendations were contrasted with actual warfarin use recorded in the Thomson Reuters Market Scan database (N = 64946). Results: 74.8% (n = 48 548) of the Marketscan AF cohort had CHADS2 of whom 14.3% had moderate/high (>= 4) ATRIA bleeding risk. While the model recommended warfarin for almost all patients with CHADS(2) >= 1 who are at low bleeding risk, it recommended warfarin for fewer patients as bleeding risk increased. Of the 44611 patients recommended warfarin, 63.4% of patients were considered warfarin exposed (concordant with model recommendation), and of the 20 335 patients recommended aspirin (acetylsalicylic acid), 59.7% received warfarin (discordant with model recommendations). Actual warfarin use decreased modestly with higher stroke risk (p < 0.0001) and with higher bleeding risk (p < 0.0001). Conclusion: High discordance between actual warfarin use and model recommendations suggests that anticoagulation decisions are not based on systematic evaluation of stroke and bleeding risks. Model-based clinical decision aids may improve oral anticoagulation decisions by more systematically weighing bleed and stroke risk. C1 [Casciano, Julian P.] EMAX Hlth Syst LLC, White Plains, NY 10601 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. [Kwong, Winghan Jacqueline] Daiichi Sankyo Inc, Hlth Econ & Outcomes Res, Parsipanny, NJ USA. [Fox, Eben S.] Daiichi Sankyo Inc, New Prod Planning, Parsipanny, NJ USA. [Martin, Bradley C.] Univ Arkansas Med Sci, Div Pharmaceut Evaluat & Policy, Little Rock, AR 72205 USA. RP Casciano, JP (reprint author), EMAX Hlth Syst LLC, 445 Hamilton Ave, White Plains, NY 10601 USA. EM juliancasciano@emaxhealth.net FU Daiichi Sankyo; Daiichi Sankyo, Inc. FX The authors wish to thank Michael Hagan DPH, MA, for assistance with study design, analysis, and review; as well as Gary Moore, MS, University of Arkansas, USA, for help in preparing the analytic extracts from the MarketScan data. They would also like to acknowledge Richert E. Goyette, D, in editing the manuscript for language accuracy, incorporating author comments, preparing and formatting the bibliography, and formatting tables and figures, which was supported by Daiichi Sankyo.; Funding sources: This study was funded by Daiichi Sankyo, Inc. NR 39 TC 12 Z9 13 U1 0 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-3277 J9 AM J CARDIOVASC DRUG JI Am. J. Cardiovasc. Drugs PY 2012 VL 12 IS 5 BP 313 EP 323 PG 11 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 009HR UT WOS:000309017400004 PM 22920047 ER PT J AU Wang, SQ Sarenac, D Chen, MH Huang, SH Giguel, FF Kuritzkes, DR Demirci, U AF Wang, ShuQi Sarenac, Dusan Chen, Michael H. Huang, Shih-Han Giguel, Francoise F. Kuritzkes, Daniel R. Demirci, Utkan TI Simple filter microchip for rapid separation of plasma and viruses from whole blood SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE microchip; filtration; virus isolation; plasma separation; point-of-care ID MICROFLUIDIC DEVICE; HIV; DIAGNOSTICS; IMMUNOASSAY; SETTINGS; SAMPLES; SWINE; ELISA; SERUM; CELL AB Sample preparation is a significant challenge for detection and sensing technologies, since the presence of blood cells can interfere with the accuracy and reliability of virus detection at the nanoscale for point-of-care testing. To the best of our knowledge, there is not an existing on-chip virus isolation technology that does not use complex fluidic pumps. Here, we presented a lab-on-a-chip filter device to isolate plasma and viruses from unprocessed whole blood based on size exclusion without using a micropump. We demonstrated that viruses (eg, HIV) can be separated on a filter-based chip (2-mu m pore size) from HIV-spiked whole blood at high recovery efficiencies of 89.9% +/- 5.0%, 80.5% +/- 4.3%, and 78.2% +/- 3.8%, for viral loads of 1000, 10,000 and 100,000 copies/mL, respectively. Meanwhile, 81.7% +/- 6.7% of red blood cells and 89.5% +/- 2.4% of white blood cells were retained on 2 mu m pore-sized filter microchips. We also tested these filter microchips with seven HIV-infected patient samples and observed recovery efficiencies ranging from 73.1% +/- 8.3% to 82.5% +/- 4.1%. These results are first steps towards developing disposable point-of-care diagnostics and monitoring devices for resource-constrained settings, as well as hospital and primary care settings. C1 [Wang, ShuQi; Sarenac, Dusan; Chen, Michael H.; Huang, Shih-Han; Demirci, Utkan] Harvard Univ, Brigham & Womens Hosp, Bioacoust MEMS Med Lab, Dept Med,Div Biomed Engn,Med Sch, Boston, MA 02115 USA. [Giguel, Francoise F.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Kuritzkes, Daniel R.] Brigham & Womens Hosp, Sect Retroviral Therapeut, Boston, MA 02115 USA. [Demirci, Utkan] Harvard MIT Hlth Sci & Technol, Bioacoust MEMS Med BAMM Labs, Cambridge, MA 02139 USA. RP Demirci, U (reprint author), Harvard MIT Hlth Sci & Technol, Bioacoust MEMS Med BAMM Labs, 65 Landsdowne St, Cambridge, MA 02139 USA. EM udemirci@rics.bwh.harvard.edu FU United States Army Medical Research and Materiel Command (USAM-RMC); Telemedicine and Advanced Technology Research Center (TATRC), at Fort Detrick, MD; [NIH R01 A1081534]; [NIH R01A1093282]; [R21 AI087107]; [NIH U54EB015408]; [R21 HL095960] FX We would like to acknowledge NIH R01 A1081534, NIH R01A1093282, R21 AI087107, NIH U54EB015408, and R21 HL095960. Also, this work was made possible by a research grant that was awarded and administered by the United States Army Medical Research and Materiel Command (USAM-RMC) and the Telemedicine and Advanced Technology Research Center (TATRC), at Fort Detrick, MD. NR 42 TC 23 Z9 23 U1 4 U2 62 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2012 VL 7 BP 5019 EP 5028 DI 10.2147/IJN.S32579 PG 10 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA 006BJ UT WOS:000308793900001 PM 23055720 ER PT J AU Chhatwal, JP Sperling, RA AF Chhatwal, Jasmeer P. Sperling, Reisa A. TI Functional MRI of Mnemonic Networks Across the Spectrum of Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Aging; Alzheimer's disease; default mode network; dementia; functional connectivity; functional magnetic resonance imaging; memory ID DEFAULT-MODE NETWORK; RESTING-STATE FMRI; TASK-INDUCED DEACTIVATION; FACE-NAME PAIRS; HIPPOCAMPAL ACTIVATION; HUMAN BRAIN; REPETITION SUPPRESSION; PARIETAL DEACTIVATION; AEROBIC GLYCOLYSIS; AMYLOID BURDEN AB Functional magnetic resonance imaging (fMRI) is a non-invasive technique that has come into common use to examine neural network function in normal and impaired cognitive states. Using this promising type of analysis, researchers have identified the presence of anatomically distributed regions operating as large-scale neural networks, which are observed both during the performance of associative memory tasks and in the resting state. The assembly of these anatomically distinct regions into functional ensembles and their choreographed activation and deactivation sets the stage for complex behaviors such as the formation and retrieval of associative memories. We review progress in the use of task-related and task-free MRI to elucidate the changes in neural activity in normal older individuals, patients with mild cognitive impairment, and those with Alzheimer's disease, focusing on the altered activity of the default mode network and medial temporal lobe. We place task-free fMRI studies into the larger context of more traditional, task-based fMRI studies of human memory, which have firmly established the critical role of the medial temporal lobe in associative encoding. Lastly, we discuss the data from our group and others that suggests task-free MRI and task-based fMRI may prove useful as non-invasive biomarkers in studying the progression of memory failure over the course of Alzheimer's disease. C1 [Chhatwal, Jasmeer P.] MGH Neurol, WACC, Boston, MA 02114 USA. [Chhatwal, Jasmeer P.; Sperling, Reisa A.] Harvard Univ, Massachusetts Gen Hosp, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment,Sch Med, Boston, MA USA. RP Chhatwal, JP (reprint author), MGH Neurol, WACC, 8th Floor,55 Fruit St, Boston, MA 02114 USA. EM jchhatwal@partners.org FU National Institute on Aging [K24 AG035007] FX The authors wish to thank Dr. Aaron Schultz for his assistance with the included figure and for helpful discussions regarding this manuscript. This work was supported by the National Institute on Aging (K24 AG035007 to RS). NR 98 TC 25 Z9 25 U1 3 U2 23 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 31 SU 3 BP S155 EP S167 DI 10.3233/JAD-2012-120730 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 011SK UT WOS:000309185100012 PM 22890098 ER PT J AU Arentoft, A Byrd, D Robbins, RN Monzones, J Miranda, C Rosario, A Coulehan, K Fuentes, A Germano, KK D'Aquila, E Sheynin, J Fraser, F Morgello, S Mindt, MR AF Arentoft, Alyssa Byrd, Desiree Robbins, Reuben N. Monzones, Jennifer Miranda, Caitlin Rosario, Ana Coulehan, Kelly Fuentes, Armando Germano, Kaori Kubo D'Aquila, Erica Sheynin, Jacob Fraser, Felicia Morgello, Susan Mindt, Monica Rivera TI Multidimensional effects of acculturation on English-language neuropsychological test performance among HIV plus Caribbean Latinas/os SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article DE Acculturation; Neuropsychology; HIV; Cognition; Latina; Latino ID AFRICAN-AMERICANS; SPEAKING; IMPAIRMENT; INFECTION; SAMPLES; SCORES; MEMORY AB Acculturation has been linked to neuropsychological performance in several ethnic groups. However, research among Latina/o samples has examined primarily Mexicans/Mexican Americans and has not examined Latina/o clinical populations of Caribbean descent. This study examined associations between a multidimensional acculturation measure and neuropsychological performance among 82 HIV+ Caribbean Latina/o adults. Multivariate results showed that US acculturation significantly predicted 11-14% of the variance in global neuropsychological functioning, verbal fluency, and processing speed, whereas Latina/o acculturation predicted 6-8% of the variance in motor and executive function (trend level associations). Both linguistic and nonlinguistic cultural factors had distinct effects on neuropsychological performance. C1 [Arentoft, Alyssa; Monzones, Jennifer; Miranda, Caitlin; Rosario, Ana; Coulehan, Kelly; Fuentes, Armando; Germano, Kaori Kubo; D'Aquila, Erica; Sheynin, Jacob; Fraser, Felicia; Mindt, Monica Rivera] Fordham Univ, Dept Psychol, New York, NY 10023 USA. [Arentoft, Alyssa] W Los Angeles VA Healthcare Ctr, Dept Psychol, Los Angeles, CA USA. [Byrd, Desiree; Morgello, Susan; Mindt, Monica Rivera] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Byrd, Desiree; Mindt, Monica Rivera] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Robbins, Reuben N.] Columbia Univ, HIV Ctr Clin & Behav Studies, Dept Psychiat, New York, NY USA. [Robbins, Reuben N.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Monzones, Jennifer] New Mexico VA Healthcare Ctr, Dept Psychol, Albuquerque, NM USA. [Rosario, Ana] NYU, Coll Arts & Sci, New York, NY USA. [Morgello, Susan] Mt Sinai Sch Med, Dept Pathol, New York, NY USA. [Morgello, Susan] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. RP Arentoft, A (reprint author), Fordham Univ, Dept Psychol, New York, NY 10023 USA. EM arentoft@fordham.edu FU NIMH [K23MH07971801, R24MH59724, U01MH083501, N01MH22005]; Northeast Consortium for Minority Faculty Development FX The authors wish to thank the Harlem Community Academic Partnership, the Manhattan HIV Care Network, and our participants for their contributions to our research. This research was supported by a K23 from NIMH (K23MH07971801) and an Early Career Development Award from the Northeast Consortium for Minority Faculty Development, both awarded to Monica Rivera Mindt; an R24 and U01 from NIMH (R24MH59724; U01MH083501) to Susan Morgello; and an N01 from NIMH (N01MH22005) subcontracted to Susan Morgello. NR 52 TC 3 Z9 3 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 EI 1744-411X J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PY 2012 VL 34 IS 8 BP 814 EP 825 DI 10.1080/13803395.2012.683856 PG 12 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 008YK UT WOS:000308992300003 PM 22624844 ER PT J AU Gologorsky, D Thanos, A Vavvas, D AF Gologorsky, Daniel Thanos, Aristomenis Vavvas, Demetrios TI Therapeutic Interventions against Inflammatory and Angiogenic Mediators in Proliferative Diabetic Retinopathy SO MEDIATORS OF INFLAMMATION LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; MONOCYTE CHEMOTACTIC PROTEIN-1; BLOOD-RETINAL BARRIER; IN-VIVO; MATRIX METALLOPROTEINASES; MACULAR DEGENERATION; MEDICAL THERAPIES; GLUCOSE CONTROL; BETA-INHIBITOR AB The global prevalence of diabetes is estimated to be 336 million people, with diabetic complications contributing to significant worldwide morbidity and mortality. Diabetic retinopathy results from cumulative microvascular damage to the retina and inflammation is recognized as a critical driver of this disease process. This paper outlines the pathophysiology leading to proliferative diabetic retinopathy and highlights many of the inflammatory, angiogenic, and cytokine mediators implicated in the development and progression of this disease. We focus a detailed discussion on the current targeted therapeutic interventions used to treat diabetic retinopathy. C1 [Gologorsky, Daniel; Thanos, Aristomenis; Vavvas, Demetrios] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Retina Serv, Boston, MA 02131 USA. RP Vavvas, D (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Retina Serv, 243 Charles St, Boston, MA 02131 USA. EM demetrios_vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 NR 87 TC 26 Z9 26 U1 1 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2012 AR 629452 DI 10.1155/2012/629452 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 013EJ UT WOS:000309288300001 ER PT J AU Maguire, CA van der Mijn, JC Degeling, MH Morse, D Tannous, BA AF Maguire, Casey A. van der Mijn, Johannes C. Degeling, Marja H. Morse, Danielle Tannous, Bakhos A. TI Codon-Optimized Luciola italica Luciferase Variants for Mammalian Gene Expression in Culture and In Vivo SO MOLECULAR IMAGING LA English DT Article ID BIOLUMINESCENT REPORTER APPLICATIONS; GENETICALLY ENCODED REPORTERS; FIREFLY LUCIFERASE; LIGHT-EMISSION; CELLS; RED; ASSAY; MUTANTS; MODELS; CANCER AB Luciferases have proven to be useful tools in advancing our understanding of biologic processes. Having a multitude of bioluminescent reporters with different properties is highly desirable. We characterized codon-optimized thermostable green- and red-emitting luciferase variants from the Italian firefly Luciola italica for mammalian gene expression in culture and in vivo. Using lentivirus vectors to deliver and stably express these luciferases in mammalian cells, we showed that both variants displayed similar levels of activity and protein half-lives as well as similar light emission kinetics and higher stability compared to the North American firefly luciferase. Further, we characterized the red-shifted variant for in vivo bioluminescence imaging. Intramuscular injection of tumor cells stably expressing this variant into nude mice yielded a robust luciferase activity. Light emission peaked at 10 minutes post-D-luciferin injection and retained >60% of signal at 1 hour. Similarly, luciferase activity from intracranially injected glioma cells expressing the red-shifted variant was readily detected and used as a marker to monitor tumor growth over time. Overall, our characterization of these codon-optimized luciferases lays the groundwork for their further use as bioluminescent reporters in mammalian cells. C1 Harvard Univ, Sch Med, Dept Neurol, Ctr Neurosci, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Vrije Univ Amsterdam Med Ctr, Ctr Canc, Dept Neurosurg, Amsterdam, Netherlands. Leiden Univ, Dept Neurosurg, Med Ctr, Leiden, Netherlands. RP Tannous, BA (reprint author), Massachusetts Gen Hosp East, Ctr Neurosci, Bldg 149,13th St, Charlestown, MA 02129 USA. EM btannous@hms.harvard.edu FU National Cancer Institute [P50 CA86355]; National Institute of Neurological Disorders [P30 NS045776]; American Brain Tumor Association Fellowship program; Fulbright scholarship; Saal van Zwanenberg Foundation; VSBfonds; Dr. Hendrik Muller Vaderlandschfonds; Dutch Cancer Foundation (KWF Kankerbestrijding); Hersenstichting brain fund; Jo Keur (Leiden hospital) FX This work was supported partly by grants from the National Cancer Institute (P50 CA86355; to B.A.T.) and the National Institute of Neurological Disorders (P30 NS045776; to B.A.T.) and the American Brain Tumor Association Fellowship program (to C.A.M.). Marja H. Degeling was supported by a Fulbright scholarship, the Saal van Zwanenberg Foundation, VSBfonds, Dr. Hendrik Muller Vaderlandschfonds, the Dutch Cancer Foundation (KWF Kankerbestrijding), the Hersenstichting brain fund as well as the Jo Keur (Leiden hospital). NR 32 TC 4 Z9 5 U1 0 U2 4 PU B C DECKER INC PI HAMILTON PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD JAN-FEB PY 2012 VL 11 IS 1 BP 13 EP 21 DI 10.2310/7290.2011.00022 PG 9 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 009TJ UT WOS:000309047800002 PM 22418023 ER PT J AU Knafo, S Gouras, GK Yan, XX Spires-Jones, T AF Knafo, Shira Gouras, Gunnar K. Yan, Xiao-Xin Spires-Jones, Tara TI Pathology of Synapses and Dendritic Spines SO NEURAL PLASTICITY LA English DT Editorial Material C1 [Knafo, Shira] CSIC, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain. [Knafo, Shira] Univ Autonoma Madrid, E-28049 Madrid, Spain. [Gouras, Gunnar K.] Lund Univ, Wallenberg Neurosci Ctr, Expt Dementia Res Unit, S-22184 Lund, Sweden. [Gouras, Gunnar K.] Lund Univ, Dept Expt Med Sci, S-22184 Lund, Sweden. [Yan, Xiao-Xin] Cent S Univ, Xiangya Sch Med, Dept Anat & Neurobiol, Changsha 410013, Hunan, Peoples R China. [Spires-Jones, Tara] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Knafo, S (reprint author), CSIC, Ctr Biol Mol Severo Ochoa, Madrid 28049, Spain. EM sknafo@cbm.uam.es RI Gouras, Gunnar/B-3021-2010; OI Gouras, Gunnar/0000-0002-5500-6325; Knafo, Shira/0000-0002-4478-7584; Spires-Jones, Tara/0000-0003-2530-0598 NR 0 TC 2 Z9 2 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0792-8483 J9 NEURAL PLAST JI Neural. Plast. PY 2012 AR 972432 DI 10.1155/2012/972432 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 013FR UT WOS:000309291800001 ER PT S AU Wang, F Flanz, J Hamm, R AF Wang, F. Flanz, J. Hamm, R. BE Steadman, SG Stephans, GSF Taylor, FE TI Injection Study of the Radiance 330 Synchrotron with a 1.6 MeV RFQ Linac SO 19TH PARTICLES AND NUCLEI INTERNATIONAL CONFERENCE (PANIC11) SE AIP Conference Proceedings LA English DT Proceedings Paper CT 19th Particles and Nuclei International Conference (PANIC) CY JUL 24-29, 2011 CL Massachusetts Inst Technol, Cambridge, MA SP Argonne Natl Lab, Brookhaven Natl Lab, CERN, DESY, GSI, Int Union Pure & Appl Phys (IUPAP), L-3 Commun Inc, Los Alamos Natl Lab, Lawrence Berkeley Natl Lab, MIT-Bates Linear Accelerator Ctr, MIT Ctr Theoret Phys (CTP), MIT Dept Phys, Natl Sci Fdn (NSF), Oak Ridge Natl Lab, Passport Syst Inc, Schlumberger, Thomas Jefferson Natl Accelerator Facil, Univ Chicago, U S Dept Energy Off Sci, MIT-LNS HO Massachusetts Inst Technol DE Proton therapy; dose rate; injector; RFQ linac; momentum acceptance; space charge limit; RF capture AB The ProTom Radiance 330 proton radiotherapy system provides the most advanced proton delivery capability to date. It supports true three-dimensional beam scanning with dynamic energy and intensity modulation. Most of the protons extracted from the synchrotron are used to treat the patient, which results in minimal neutron background in the treatment room. The patient dose rate depends upon the number of protons injected and the acceleration cycle time. Therefore, one can boost the dose rate by increasing the beam intensity at injection. Improvements to the existing tandem accelerator injector are already underway. However, an alternative way to attain higher intensity beam is to use an RFQ linac as an injector. To this end, a novel 1.6 MeV RFQ linac has been designed to specifically satisfy the small energy acceptance limits of the synchrotron. Simulations of the beam line optics and injection matching to the synchrotron have been performed using the computer codes PARMILA and TRACE-3D to determine if an additional bunching cavity is needed. Assessments of the space charge limit at the relatively low injection energy of 1.6 MeV and RF capture simulations have also been performed. Results of these studies are presented. C1 [Wang, F.] MIT Bates Linear Accelerator Ctr, POB 849, Middleton, MA 01949 USA. [Flanz, J.] Massachusetts Gen Hosp, Proton Therapy Ctr, Boston, MA 02114 USA. [Hamm, R.] R&M Tech Enterprises, Pleasanton, CA 94566 USA. RP Wang, F (reprint author), MIT Bates Linear Accelerator Ctr, POB 849, Middleton, MA 01949 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1036-7 J9 AIP CONF PROC PY 2012 VL 1441 BP 649 EP 651 DI 10.1063/1.3700643 PG 3 WC Physics, Applied; Physics, Particles & Fields SC Physics GA BBI40 UT WOS:000306963900169 ER PT B AU Pella, RD Hill, BD Singh, AN Hayes, JS Gouvier, WD AF Pella, Russell D. Hill, B. D. Singh, Ashvind N. Hayes, Jill S. Gouvier, Wm Drew BE Reynolds, CR Horton, AM TI Noncredible Performance in Mild Traumatic Brain Injury SO DETECTION OF MALINGERING DURING HEAD INJURY LITIGATION, SECOND EDITION LA English DT Article; Book Chapter ID POSTTRAUMATIC-STRESS-DISORDER; VERBAL-LEARNING TEST; SYMPTOM VALIDITY TEST; CLOSED-HEAD-INJURY; MALINGERED NEUROCOGNITIVE DYSFUNCTION; ADULT INTELLIGENCE SCALE; RELIABLE DIGIT SPAN; CARD SORTING TEST; MEMORY TEST WCMT; RESPONSE BIAS C1 [Pella, Russell D.; Gouvier, Wm Drew] Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. [Singh, Ashvind N.] Metropolitan State Hosp, Norwalk, CA 91325 USA. [Hill, B. D.] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Providence, RI USA. [Pella, Russell D.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Gouvier, WD (reprint author), Louisiana State Univ, Dept Psychol, Baton Rouge, LA 70803 USA. EM wgouvie@lsu.edu OI Hill, Benjamin/0000-0002-5797-5082 NR 239 TC 6 Z9 6 U1 5 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4614-0441-5 PY 2012 BP 121 EP 150 DI 10.1007/978-1-4614-0442-2_3 D2 10.1007/978-1-4614-0442-2 PG 30 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA BAD69 UT WOS:000303852000003 ER PT S AU Esan, A Hess, D Sessler, C George, L Oribabor, C Khusid, F Raoof, S AF Esan, A. Hess, D. Sessler, C. George, L. Oribabor, C. Khusid, F. Raoof, S. BE Ferrer, M Pelosi, P TI Ventilator strategies in severe hypoxaemic respiratory failure SO NEW DEVELOPMENTS IN MECHANICAL VENTILATION SE European Respiratory Monograph LA English DT Article; Book Chapter DE Acute respiratory distress syndrome; alternative ventilator modes; hypoxaemic respiratory failure; mechanical ventilation; rescue strategies; ventilator strategies ID ACUTE LUNG INJURY; FREQUENCY OSCILLATORY VENTILATION; PRESSURE RELEASE VENTILATION; END-EXPIRATORY PRESSURE; INVERSE RATIO VENTILATION; CONVENTIONAL MECHANICAL VENTILATION; RANDOMIZED CONTROLLED-TRIAL; TIDAL VOLUME VENTILATION; ELECTRICAL-IMPEDANCE TOMOGRAPHY; DISTRESS-SYNDROME PATIENTS AB Mechanical ventilation of patients with acute lung injury/acute respiratory distress syndrome (ARDS) should commence with low tidal volume (VT), low stretch and adequate positive end-expiratory pressure (PEEP), as proposed by the first ARDSnet trial. The majority of patients with ARDS will achieve their goals of oxygenation and plateau pressure, utilising the lung protective strategy. In the remaining minority of patients, these end-points may not be achieved. Such patients have a significantly high mortality and should be considered for rescue strategies relatively early on. If the patients respond positively to lung recruitment trials, using rescue strategies may open atelectactic alveoli and allow oxygenation or plateau pressure targets to be achieved. None of these rescue strategies have been shown to reduce mortality, although short-term objectives of improvement in oxygenation or reduction in plateau pressures may be achieved. Therefore, the selection of these strategies should be based on availability and level of comfort of the operators. C1 [Esan, A.; George, L.; Raoof, S.] New York Methodist Hosp, Dept Pulm & Crit Care, Brooklyn, NY 11215 USA. [Oribabor, C.] New York Methodist Hosp, Dept Cardiothorac Surg, Brooklyn, NY 11215 USA. [Khusid, F.] New York Methodist Hosp, Dept Resp Therapy, Brooklyn, NY 11215 USA. [Hess, D.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Sessler, C.] Med Coll Virginia Hosp, Richmond, VA USA. RP Esan, A (reprint author), New York Methodist Hosp, Dept Pulm & Crit Care, 506 6th St, Brooklyn, NY 11215 USA. EM bayoesan@yahoo.com NR 175 TC 1 Z9 1 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOCIETY PI SHEFFIELD PA 442 GLOSSOP ROAD, SHEFFIELD, S10 2PX, ENGLAND SN 2075-6674 BN 978-1-84984-022-4 J9 EUR RESPIR MONOGR PY 2012 IS 55 BP 19 EP 39 DI 10.1183/1025448x.10000412 PG 21 WC Respiratory System SC Respiratory System GA BBM40 UT WOS:000307362600004 ER PT S AU Bassi, GL Ferrer, M Ranzani, OT Marti, JD Berra, L Fernandez, L Torres, A AF Bassi, G. Li Ferrer, M. Ranzani, O. T. Marti, J-D. Berra, L. Fernandez, L. Torres, A. BE Ferrer, M Pelosi, P TI Prevention of VAP: role of the artificial airway, body position and setting the ventilator SO NEW DEVELOPMENTS IN MECHANICAL VENTILATION SE European Respiratory Monograph LA English DT Article; Book Chapter DE Endotracheal tube; mechanical ventilator; mucus; positive end-expiratory pressure; semi-recumbent position; ventilator-associated pneumonia ID TRACHEAL TUBE CUFF; INTENSIVE-CARE-UNIT; SUBGLOTTIC SECRETION DRAINAGE; LIQUID FLOW MECHANISM; REDUCES PULMONARY ASPIRATION; COATED ENDOTRACHEAL-TUBES; LOW-PRESSURE CUFF; RESPIRATORY-TRACT; BACTERIAL-COLONIZATION; NOSOCOMIAL PNEUMONIA AB Ventilator associated pneumonia (VAP) is associated with increased morbidity, mortality and burden for the healthcare system. Oropharyngeal secretions, pooled above the endotracheal tube (ETT) cuff, are the primary source of pathogens in this iatrogenic infection. Improvements in the ETT cuff design to achieve tracheal sealing and maintaining the internal cuff pressure within the recommended range (25-30 cmH(2)O) have a pivotal role in the prevention of pulmonary aspiration of colonised oropharyngeal secretions and VAP. Additionally, ETTs coated with antimicrobial agents prevent colonisation of their internal lumen and biofilm formation; however, further evidence is necessary to assess the role of biofilm in the pathogenesis of VAP. The semirecumbent position is universally recommended; yet, laboratory studies challenge the benefits of such a position. Finally, during positive pressure ventilation, the ventilatory parameters that influence the inspiratory flow, i.e. the duty cycle, have a significant effect on retention of mucus and, potentially, on risks of lung infections. Further clinical evidence is necessary to assess benefits and limitations of ventilatory settings on VAP prevention. C1 [Torres, A.] Hosp Clin Barcelona, Serv Pneumol & Al Lergia Resp, Resp Intens Care Unit, Thorax Inst, Barcelona 08036, Spain. [Bassi, G. Li; Ferrer, M.; Fernandez, L.; Torres, A.] Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain. [Bassi, G. Li; Ferrer, M.; Marti, J-D.; Fernandez, L.; Torres, A.] Ctr Invest Biomed Red Enfermedades Resp CIBERES, Barcelona, Spain. [Ranzani, O. T.] Univ Sao Paulo, Fac Med, Resp Intens Care Unit, Pulm Div,Heart Inst InCor, Sao Paulo, Brazil. [Berra, L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia Crit Care & Pain Med, Boston, MA USA. RP Torres, A (reprint author), Hosp Clin Barcelona, Serv Pneumol & Al Lergia Resp, Resp Intens Care Unit, Thorax Inst, Calle Villarroel 170,Esc 6-8,Planta 2, Barcelona 08036, Spain. EM atorres@clinic.ub.es OI Ranzani, Otavio/0000-0002-4677-6862 NR 98 TC 0 Z9 0 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOCIETY PI SHEFFIELD PA 442 GLOSSOP ROAD, SHEFFIELD, S10 2PX, ENGLAND SN 2075-6674 BN 978-1-84984-022-4 J9 EUR RESPIR MONOGR PY 2012 IS 55 BP 153 EP 168 DI 10.1183/1025448x.10002511 PG 16 WC Respiratory System SC Respiratory System GA BBM40 UT WOS:000307362600014 ER PT B AU Wolfe, JM Kluender, KR Levi, DM Bartoshuk, LM Herz, RS Klatzky, R Lederman, SJ Merfeld, DM AF Wolfe, Jeremy M. Kluender, Keith R. Levi, Dennis M. Bartoshuk, Linda M. Herz, Rachel S. Klatzky, Roberta Lederman, Susan J. Merfeld, Daniel M. TI Sensation & Perception, Third Edition SO SENSATION & PERCEPTION, THIRD EDITION LA English DT Article; Book ID PRIMARY VISUAL-CORTEX; HUMAN EXTRASTRIATE CORTEX; 6-N-PROPYLTHIOURACIL PROP BITTERNESS; INNERVATING SEMICIRCULAR CANALS; SQUIRRELS SPERMOPHILUS-BEECHEYI; TACTILE OBJECT RECOGNITION; FIGURE-GROUND ORGANIZATION; BINOCULAR DEPTH-PERCEPTION; OCULAR DOMINANCE COLUMNS; HEARING ILLUSORY SOUNDS C1 [Wolfe, Jeremy M.; Merfeld, Daniel M.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Kluender, Keith R.] Univ Wisconsin, Madison, WI 53706 USA. [Levi, Dennis M.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Bartoshuk, Linda M.] Univ Florida, Dept Community Dent & Behav Sci, Gainesville, FL 32611 USA. [Herz, Rachel S.] Brown Univ, Providence, RI 02912 USA. [Klatzky, Roberta] Carnegie Mellon Univ, Ctr Neural Basis Cognit & Human, Comp Interact Inst, Pittsburgh, PA 15213 USA. [Lederman, Susan J.] Queens Univ, Ctr Neurosci, Kingston, ON K7L 3N6, Canada. [Wolfe, Jeremy M.] MIT, Cambridge, MA 02139 USA. [Levi, Dennis M.] Helen Wills Neurosci Inst, Sch Optometry & Prof, Berkeley, CA USA. [Lederman, Susan J.] Queens Univ, Sch Comp, Kingston, ON K7L 3N6, Canada. [Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA USA. RP Wolfe, JM (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Wolfe, Jeremy/C-1621-2012 OI Wolfe, Jeremy/0000-0002-6475-1984 NR 790 TC 14 Z9 14 U1 4 U2 13 PU SINAUER ASSOC PI SUNDERLAND PA SINAUER ASSOC, SUNDERLAND, MA 01375 USA BN 978-0-87893-572-7 PY 2012 BP 2 EP + PG 466 WC Neurosciences SC Neurosciences & Neurology GA BZO67 UT WOS:000302260700001 ER PT J AU Wimmer, NJ Yeh, RW AF Wimmer, Neil J. Yeh, Robert W. TI Another View of Personalized Medicine: Optimizing Stent Selection on the Basis of Predicted Benefit in Percutaneous Coronary Intervention SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID DRUG-ELUTING STENT; DUAL-ANTIPLATELET THERAPY; BARE-METAL STENTS; TARGET LESION REVASCULARIZATION; BALLOON ANGIOPLASTY; RESTENOSIS; IMPLANTATION; MULTICENTER; TRIAL; CLOPIDOGREL AB Drug-eluting stents (DES) decrease the risk of restenosis compared to bare metal stews (BMS) for percutaneous coronary intervention (PCI). However, their use requires patients to take prolonged dual antiplatelet therapy that increases bleeding risk and without which, patients have an increased risk of developing stent thrombosis. In light of these competing risks, understanding which patients derive the greatest benefit of DES compared to BMS is essential for guiding therapy. We review recent efforts to predict the magnitude of the restenosis benefit of DES compared to BMS for individual patients. Understanding and predicting the likelihood of benefit for individual patients is essential to rational decision making with regard to the type of stew to use during PCI and will serve to increase the value of the health care that clinicians deliver. (Trends Cardiovasc Med 2012;22:23-28) (c) 2012 Elsevier Inc. All rights reserved. C1 [Yeh, Robert W.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Dept Med,Med Sch, Boston, MA 02114 USA. [Wimmer, Neil J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02155 USA. RP Yeh, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Dept Med,Med Sch, GRB 843, Boston, MA 02114 USA. EM ryeh@partners.org FU NHLBI NIH HHS [T32 HL007604] NR 32 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JAN PY 2012 VL 22 IS 1 BP 23 EP 28 AR PII S1050-1738(12)00175-2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 007RK UT WOS:000308905600005 PM 22841840 ER PT J AU Bongiovanni, M Spitale, A Faquin, WC Mazzucchelli, L Baloch, ZW AF Bongiovanni, Massimo Spitale, Alessandra Faquin, William C. Mazzucchelli, Luca Baloch, Zubair W. TI The Bethesda System for Reporting Thyroid Cytopathology: A Meta-Analysis SO ACTA CYTOLOGICA LA English DT Review DE Bethesda; Thyroid fine-needle aspiration; Meta-analysis ID FINE-NEEDLE-ASPIRATION; MALIGNANCY RISK; NODULES; MANAGEMENT; CLASSIFICATION; TERMINOLOGY; DIAGNOSIS; BIOPSIES; LESIONS; CANCER AB Objective:We aimed to investigate the validity of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) through meta-analysis. Study Design: All publications between January 1, 2008 and September 1, 2011 that studied TBSRTC and had available histological follow-up data were retrieved. To calculate the sensitivity, specificity and diagnostic accuracy, the cases diagnosed as follicular neoplasm, suspicious for malignancy and malignant which were histopathologically confirmed as malignant were defined as true-positive. True-negative included benign cases confirmed as benign on histopathology. The nondiagnostic category was excluded from the statistical calculation. The correlations between the 6 diagnostic categories were investigated. Results: The publications review resulted in a case cohort of 25,445 thyroid fine-needle aspirations, 6,362 (25%) of which underwent surgical excision; this group constituted the basis of the study. The sensitivity, specificity and diagnostic accuracy were 97, 50.7 and 68.8%, respectively. The positive predictive value and negative predictive value were 55.9 and 96.3%, respectively. The rates of false negatives and false positives were low: 3 and 0.5%, respectively. Conclusions: The results of meta-analysis showed high overall accuracy, indicating that TBSRTC represents a reliable and valid reporting system for thyroid cytology. Copyright (c) 2012 S. Karger AG, Basel C1 [Baloch, Zubair W.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Faquin, William C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bongiovanni, Massimo; Spitale, Alessandra; Mazzucchelli, Luca] Inst Pathol, Locarno, Switzerland. RP Baloch, ZW (reprint author), Hosp Univ Penn, Dept Pathol & Lab Med, 3400 Spruce St,6 Founders Pavil, Philadelphia, PA 19104 USA. EM baloch@mail.med.upenn.edu RI Bongiovanni, Massimo/C-3144-2017 OI Bongiovanni, Massimo/0000-0001-9846-6682 NR 35 TC 150 Z9 161 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PY 2012 VL 56 IS 4 BP 333 EP 339 DI 10.1159/000339959 PG 7 WC Pathology SC Pathology GA 001GQ UT WOS:000308449000001 PM 22846422 ER PT S AU Hwang, I Sheen, J Muller, B AF Hwang, Ildoo Sheen, Jen Mueller, Bruno BE Merchant, SS TI Cytokinin Signaling Networks SO ANNUAL REVIEW OF PLANT BIOLOGY, VOL 63 SE Annual Review of Plant Biology LA English DT Review; Book Chapter DE auxin; embryo; meristem; vasculature; nodulation; immunity; stress; senescence ID B RESPONSE REGULATORS; SHOOT APICAL MERISTEM; TO-ASP PHOSPHORELAY; HISTIDINE PHOSPHOTRANSFER PROTEINS; FEMALE GAMETOPHYTE DEVELOPMENT; POLAR AUXIN TRANSPORT; ARABIDOPSIS-THALIANA; LEAF SENESCENCE; ROOT-MERISTEM; EXTRACELLULAR INVERTASE AB Despite long-standing observations on diverse cytokinin actions, the discovery path to cytokinin signaling mechanisms was tortuous. Unyielding to conventional genetic screens, experimental innovations were paramount in unraveling the core cytokinin signaling circuitry, which employs a large repertoire of genes with overlapping and specific functions. The canonical two-component transcription circuitry involves His kinases that perceive cytokinin and initiate signaling, as well as His-to-Asp phosphorelay proteins that transfer phosphoryl groups to response regulators, transcriptional activators, or repressors. Recent advances have revealed the complex physiological functions of cytokinins, including interactions with auxin and other signal transduction pathways. This review begins by outlining the historical path to cytokinin discovery and then elucidates the diverse cytokinin functions and key signaling components. Highlights focus on the integration of cytokinin signaling components into regulatory networks in specific contexts, ranging from molecular, cellular, and developmental regulations in the embryo, root apical meristem, shoot apical meristem, stem and root vasculature, and nodule organogenesis to organismal responses underlying immunity, stress tolerance, and senescence. C1 [Hwang, Ildoo] Pohang Univ Sci & Technol, Dept Life Sci, Pohang 790784, South Korea. [Sheen, Jen] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Sheen, Jen] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Sheen, Jen] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Mueller, Bruno] Univ Zurich, Inst Plant Biol, Zurich Basel Plant Sci Ctr, CH-8008 Zurich, Switzerland. RP Hwang, I (reprint author), Pohang Univ Sci & Technol, Dept Life Sci, Pohang 790784, South Korea. EM ihwang@postech.ac.kr; sheen@molbio.mgh.harvard.edu; bruno.mueller@uzh.ch RI Mueller, Bruno/E-9888-2017 OI Mueller, Bruno/0000-0003-2664-7219 NR 152 TC 170 Z9 178 U1 25 U2 183 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1543-5008 BN 978-0-8243-0663-2 J9 ANNU REV PLANT BIOL JI Annu. Rev. Plant Biol. PY 2012 VL 63 BP 353 EP 380 PG 28 WC Plant Sciences SC Plant Sciences GA BBR06 UT WOS:000307953100015 PM 22554243 ER PT J AU Boelen, PA Prigerson, HG AF Boelen, Paul A. Prigerson, Holly G. TI COMMENTARY ON THE INCLUSION OF PERSISTENT COMPLEX BEREAVEMENT-RELATED DISORDER IN DSM-5 SO DEATH STUDIES LA English DT Article ID COMPLICATED-GRIEF; MENTAL-DISORDER; TRAUMATIC GRIEF; PROLONGED GRIEF; RISK; RESILIENCE; CONSTRUCTS; COGNITIONS; ADJUSTMENT; AVOIDANCE AB The DSM-5 Anxiety, Obsessive-Compulsive Spectrum, Posttraumatic, and Dissociative Disorders Work Group has proposed criteria for Persistent Complex Bereavement-Related Disorder (PCBRD) for inclusion in the appendix of DSM-5. The authors feel that it is important that dysfunctional grief will become a formal condition in DSM-5 because that would facilitate research and would imply recognition of the suffering of a significant minority of bereaved individuals who experience difficulties in their process of recovery from loss. However, as detailed in this commentary, we oppose the inclusion of the proposed criteria set for PCBRD for several reasons, including the fact that these criteria lack empirical evidence. In our view, it is better to include empirically validated criteria for prolonged grief disorder in DSM-5, possibly expanded with a few symptom criteria that are tapped by the Inventory of Complicated Grief, the most widely used instrument to measure dysfunctional grief. C1 [Boelen, Paul A.] Univ Utrecht, Dept Clin & Hlth Psychol, NL-3508 TC Utrecht, Netherlands. [Prigerson, Holly G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychosocial Epidemiol & Outcomes Res, Boston, MA 02115 USA. RP Boelen, PA (reprint author), Univ Utrecht, Dept Clin & Hlth Psychol, POB 80140, NL-3508 TC Utrecht, Netherlands. EM P.A.Boelen@uu.nl NR 46 TC 22 Z9 27 U1 2 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0748-1187 J9 DEATH STUD JI Death Stud. PY 2012 VL 36 IS 9 BP 771 EP 794 DI 10.1080/07481187.2012.706982 PG 24 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA 998OG UT WOS:000308249200001 PM 24563927 ER PT J AU Dickerson, B Domoto-Reilly, K Brickhouse, M Urbano, MP Leong, JK Rosen, HJ AF Dickerson, Brad Domoto-Reilly, Kimiko Brickhouse, Michael Urbano, Marissa P. Leong, Josiah K. Rosen, Howard J. TI MRI markers of FTD for use in clinical trials: Initial quantitative MRI results from FTLDNI SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Meeting Abstract CT 8th International Conference on Frontotemporal Dementias CY SEP 05-07, 2012 CL Manchester, ENGLAND C1 [Dickerson, Brad; Domoto-Reilly, Kimiko; Brickhouse, Michael] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Urbano, Marissa P.; Leong, Josiah K.; Rosen, Howard J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2012 VL 33 SU 1 BP 164 EP 164 PG 1 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 003LG UT WOS:000308612400234 ER PT J AU Giannoukos, G Ciulla, DM Huang, K Haas, BJ Izard, J Levin, JZ Livny, J Earl, AM Gevers, D Ward, DV Nusbaum, C Birren, BW Gnirke, A AF Giannoukos, Georgia Ciulla, Dawn M. Huang, Katherine Haas, Brian J. Izard, Jacques Levin, Joshua Z. Livny, Jonathan Earl, Ashlee M. Gevers, Dirk Ward, Doyle V. Nusbaum, Chad Birren, Bruce W. Gnirke, Andreas TI Efficient and robust RNA-seq process for cultured bacteria and complex community transcriptomes SO GENOME BIOLOGY LA English DT Article ID MARINE CYANOBACTERIUM PROCHLOROCOCCUS; DUPLEX-SPECIFIC NUCLEASE; RIBOSOMAL-RNA; MICROBIAL METATRANSCRIPTOMICS; GENE-EXPRESSION; LIGHT; OCEAN; TEMPERATURE; SEQUENCES; LIBRARIES AB We have developed a process for transcriptome analysis of bacterial communities that accommodates both intact and fragmented starting RNA and combines efficient rRNA removal with strand-specific RNA-seq. We applied this approach to an RNA mixture derived from three diverse cultured bacterial species and to RNA isolated from clinical stool samples. The resulting expression profiles were highly reproducible, enriched up to 40-fold for non-rRNA transcripts, and correlated well with profiles representing undepleted total RNA. C1 [Giannoukos, Georgia; Ciulla, Dawn M.; Huang, Katherine; Haas, Brian J.; Levin, Joshua Z.; Livny, Jonathan; Earl, Ashlee M.; Gevers, Dirk; Ward, Doyle V.; Nusbaum, Chad; Birren, Bruce W.; Gnirke, Andreas] Broad Inst MIT & Harvard, Genome Sequencing & Anal Program, Cambridge, MA 02141 USA. [Izard, Jacques] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Izard, Jacques] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Giannoukos, G (reprint author), Broad Inst MIT & Harvard, Genome Sequencing & Anal Program, 320 Charles St & 301 Binney St, Cambridge, MA 02141 USA. EM ggiannou@broadinstitute.org OI Earl, Ashlee/0000-0001-7857-9145; Izard, Jacques/0000-0002-5904-5436 FU National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health and Human Services [HHSN272200900018C]; Human Microbiome Project [U54 HG004969]; NIAID [AI076608]; National Cancer Institute [CA139193] FX We thank Cris Kinross and Epicentre for Ribo-Zero kits in advance of the commercial release, Steven Kain and NuGEN Technologies for providing the Ovation Prokaryotic RNA-Seq System, Sallie (Penny) Chisholm and her lab, especially Allison Coe, for culturing Prochlorococcus marinus, Mellie Vizsla for a stool sample to test collection, preservation and RNA/DNA extraction procedures, Xian Adiconis for cDNA lab protocols, the staff of the Broad Institute Sequencing Platform for generating sequencing data, and James Bochicchio and Cristyn Kells for their assistance with the submission of data to the SRA. We also thank Lesley Gaffney for last- minute help with the artwork. This project has been funded in part with funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health and Human Services under contract number HHSN272200900018C, the Human Microbiome Project (U54 HG004969), the NIAID under award AI076608 to JL, and National Cancer Institute under award CA139193 to JI. NR 44 TC 77 Z9 79 U1 2 U2 69 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 3 AR r23 DI 10.1186/gb-2012-13-3-r23 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002PL UT WOS:000308544200008 PM 22455878 ER PT J AU Shao, Z Zhang, YJ Yuan, GC Orkin, SH Waxman, DJ AF Shao, Zhen Zhang, Yijing Yuan, Guo-Cheng Orkin, Stuart H. Waxman, David J. TI MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets SO GENOME BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; TRANSCRIPTION FACTOR-BINDING; GENOME-WIDE ANALYSIS; CHROMATIN OCCUPANCY; GENE-EXPRESSION; MICROARRAY DATA; LINEAR-MODELS; REVEALS; SITES; NORMALIZATION AB ChIP-Seq is widely used to characterize genome-wide binding patterns of transcription factors and other chromatin-associated proteins. Although comparison of ChIP-Seq data sets is critical for understanding cell type-dependent and cell state-specific binding, and thus the study of cell-specific gene regulation, few quantitative approaches have been developed. Here, we present a simple and effective method, MAnorm, for quantitative comparison of ChIP-Seq data sets describing transcription factor binding sites and epigenetic modifications. The quantitative binding differences inferred by MAnorm showed strong correlation with both the changes in expression of target genes and the binding of cell type-specific regulators. C1 [Shao, Zhen; Yuan, Guo-Cheng; Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Shao, Zhen; Yuan, Guo-Cheng; Orkin, Stuart H.] Dana Farber Canc Inst, Dept Computat Biol, Boston, MA 02115 USA. [Shao, Zhen; Orkin, Stuart H.] Childrens Hosp, Div Pediat Hematol Oncol, Karp Family Res Labs, Boston, MA 02115 USA. [Zhang, Yijing; Waxman, David J.] Boston Univ, Div Cell & Mol Biol, Dept Biol, Boston, MA 02215 USA. [Orkin, Stuart H.] Childrens Hosp, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM orkin@bloodgroup.tch.harvard.edu; djw@bu.edu RI cheng, yong/I-4270-2012; OI Waxman, David/0000-0001-7982-9206 FU NHGRI NIH HHS [R01 HG005085, R01 HG005085-02]; NIDDK NIH HHS [R01 DK033765] NR 41 TC 69 Z9 69 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 3 AR R16 DI 10.1186/gb-2012-13-3-r16 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002PL UT WOS:000308544200001 PM 22424423 ER PT J AU Yusuf, D Butland, SL Swanson, MI Bolotin, E Ticoll, A Cheung, WA Zhang, XYC Dickman, CTD Fulton, DL Lim, JS Schnabl, JM Ramos, OHP Vasseur-Cognet, M de Leeuw, CN Simpson, EM Ryffel, GU Lam, EWF Kist, R Wilson, MSC Marco-Ferreres, R Brosens, JJ Beccari, LL Bovolenta, P Benayoun, BA Monteiro, LJ Schwenen, HDC Grontved, L Wederell, E Mandrup, S Veitia, RA Chakravarthy, H Hoodless, PA Mancarelli, MM Torbett, BE Banham, AH Reddy, SP Cullum, RL Liedtke, M Tschan, MP Vaz, M Rizzino, A Zannini, M Frietze, S Farnham, PJ Eijkelenboom, A Brown, PJ Laperriere, D Leprince, D de Cristofaro, T Prince, KL Putker, M del Peso, L Camenisch, G Wenger, RH Mikula, M Rozendaal, M Mader, S Ostrowski, J Rhodes, SJ Van Rechem, C Boulay, G Olechnowicz, SWZ Breslin, MB Lan, MS Nanan, KK Wegner, M Hou, J Mullen, RD Colvin, SC Noy, PJ Webb, CF Witek, ME Ferrell, S Daniel, JM Park, J Waldman, SA Peet, DJ Taggart, M Jayaraman, PS Karrich, JJ Blom, B Vesuna, F O'Geen, H Sun, YF Gronostajski, RM Woodcroft, MW Hough, MR Chen, E Europe-Finner, GN Karolczak-Bayatti, M Bailey, J Hankinson, O Raman, V LeBrun, DP Biswal, S Harvey, CJ DeBruyne, JP Hogenesch, JB Hevner, RF Heligon, C Luo, XM Blank, MC Millen, KJ Sharlin, DS Forrest, D Dahlman-Wright, K Zhao, CY Mishima, Y Sinha, S Chakrabarti, R Portales-Casamar, E Sladek, FM Bradley, PH Wasserman, WW AF Yusuf, Dimas Butland, Stefanie L. Swanson, Magdalena I. Bolotin, Eugene Ticoll, Amy Cheung, Warren A. Zhang, Xiao Yu Cindy Dickman, Christopher T. D. Fulton, Debra L. Lim, Jonathan S. Schnabl, Jake M. Ramos, Oscar H. P. Vasseur-Cognet, Mireille de Leeuw, Charles N. Simpson, Elizabeth M. Ryffel, Gerhart U. Lam, Eric W-F Kist, Ralf Wilson, Miranda S. C. Marco-Ferreres, Raquel Brosens, Jan J. Beccari, Leonardo L. Bovolenta, Paola Benayoun, Berenice A. Monteiro, Lara J. Schwenen, Helma D. C. Grontved, Lars Wederell, Elizabeth Mandrup, Susanne Veitia, Reiner A. Chakravarthy, Harini Hoodless, Pamela A. Mancarelli, M. Michela Torbett, Bruce E. Banham, Alison H. Reddy, Sekhar P. Cullum, Rebecca L. Liedtke, Michaela Tschan, Mario P. Vaz, Michelle Rizzino, Angie Zannini, Mariastella Frietze, Seth Farnham, Peggy J. Eijkelenboom, Astrid Brown, Philip J. Laperriere, David Leprince, Dominique de Cristofaro, Tiziana Prince, Kelly L. Putker, Marrit del Peso, Luis Camenisch, Gieri Wenger, Roland H. Mikula, Michal Rozendaal, Marieke Mader, Sylvie Ostrowski, Jerzy Rhodes, Simon J. Van Rechem, Capucine Boulay, Gaylor Olechnowicz, Sam W. Z. Breslin, Mary B. Lan, Michael S. Nanan, Kyster K. Wegner, Michael Hou, Juan Mullen, Rachel D. Colvin, Stephanie C. Noy, Peter John Webb, Carol F. Witek, Matthew E. Ferrell, Scott Daniel, Juliet M. Park, Jason Waldman, Scott A. Peet, Daniel J. Taggart, Michael Jayaraman, Padma-Sheela Karrich, Julien J. Blom, Bianca Vesuna, Farhad O'Geen, Henriette Sun, Yunfu Gronostajski, Richard M. Woodcroft, Mark W. Hough, Margaret R. Chen, Edwin Europe-Finner, G. Nicholas Karolczak-Bayatti, Magdalena Bailey, Jarrod Hankinson, Oliver Raman, Venu LeBrun, David P. Biswal, Shyam Harvey, Christopher J. DeBruyne, Jason P. Hogenesch, John B. Hevner, Robert F. Heligon, Christophe Luo, Xin M. Blank, Marissa Cathleen Millen, Kathleen Joyce Sharlin, David S. Forrest, Douglas Dahlman-Wright, Karin Zhao, Chunyan Mishima, Yuriko Sinha, Satrajit Chakrabarti, Rumela Portales-Casamar, Elodie Sladek, Frances M. Bradley, Philip H. Wasserman, Wyeth W. TI The Transcription Factor Encyclopedia SO GENOME BIOLOGY LA English DT Article ID PROTEIN DATA-BANK; MENDELIAN-INHERITANCE; GENE-REGULATION; DATABASE; INFORMATION; ANNOTATION; WIKI; KNOWLEDGEBASE; EVOLUTION; UPDATE AB Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe. C1 [Yusuf, Dimas; Butland, Stefanie L.; Zhang, Xiao Yu Cindy; Lim, Jonathan S.; de Leeuw, Charles N.; Simpson, Elizabeth M.; Portales-Casamar, Elodie; Wasserman, Wyeth W.] Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Fac Med,Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada. [Swanson, Magdalena I.] Fraser Hlth Author, Evaluat Serv, Surrey, BC V3R 7P8, Canada. [Swanson, Magdalena I.] Fraser Hlth Author, Res Serv, Surrey, BC V3R 7P8, Canada. [Bolotin, Eugene] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Ticoll, Amy; Bradley, Philip H.] Fred Hutchinson Canc Res Ctr, Computat Biol Program, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Cheung, Warren A.] Univ British Columbia, Dept Bioinformat, Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada. [Dickman, Christopher T. D.] Univ Western Ontario, Dept Biol, London, ON N6A 5B7, Canada. [Fulton, Debra L.] Univ British Columbia, Genet Program, Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada. [Schnabl, Jake M.; Sladek, Frances M.] Univ Calif Riverside, Inst Integrated Genome Biol, Riverside, CA 92521 USA. [Ramos, Oscar H. P.] CEA, SIMOPRO, Lab Life Sci, F-91191 Saclay, Ile De France, France. [Vasseur-Cognet, Mireille] Inst Cochin, Dept Endocrinol Metab & Canc, INSERM, U1016, F-75014 Paris, Ile De France, France. [Ryffel, Gerhart U.] Univ Duisburg Essen, Inst Zellbiol, Univ Klinikum Essen, D-45122 Essen, Nordrhein Westf, Germany. [Lam, Eric W-F; Wilson, Miranda S. C.; Monteiro, Lara J.; Schwenen, Helma D. C.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Div Canc, London W12 0NN, England. [Kist, Ralf] Newcastle Univ, Ctr Oral Hlth Res, Sch Dent Sci, Sch Med, Newcastle Upon Tyne NE2 4BW, Tyne & Wear, England. [Marco-Ferreres, Raquel; Bovolenta, Paola] CSIC, Dept Dev & Differentiat, CBMSO, E-28049 Madrid, Spain. [Marco-Ferreres, Raquel; Beccari, Leonardo L.; Bovolenta, Paola] CIBERER, Madrid 28049, Spain. [Brosens, Jan J.] Univ Warwick, Div Reprod Hlth, Warwick Med Sch, Coventry CV2 2DX, W Midlands, England. [Benayoun, Berenice A.] Univ Paris 07, Dept Mol & Cellular Pathol, Inst Jacques Monod, F-75013 Paris, Ile De France, France. [Grontved, Lars; Mandrup, Susanne] Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense, Region Syddanma, Denmark. [Wederell, Elizabeth; Hoodless, Pamela A.; Cullum, Rebecca L.; Hou, Juan] BC Canc Agcy, Prov Hlth Serv Author, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. [Veitia, Reiner A.] Univ Paris 07, Inst Jacques Monod, Mol & Cellular Pathol Program, F-75013 Paris, Ile De France, France. [Chakravarthy, Harini; Rizzino, Angie] Univ Nebraska, Eppley Inst Res Canc & Allied Dis, Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Mancarelli, M. Michela] Scripps Res Inst, Dept Mol Expt Med, La Jolla, CA 92037 USA. [Torbett, Bruce E.] Scripps Res Inst, Dept Immunol & Microbial Sci MEM 131, La Jolla, CA 92037 USA. [Torbett, Bruce E.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. [Banham, Alison H.] Univ Oxford, Nuffield Dept Clin Lab Sci, John Radcliffe Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 9DU, Oxon, England. [Reddy, Sekhar P.] Univ Illinois, Dept Pediat, Coll Med, Chicago, IL 60612 USA. [Liedtke, Michaela] Stanford Univ, Sch Med, Dept Med Hematol, Stanford, CA 94305 USA. [Tschan, Mario P.] Univ Bern, Dept Med, CH-3012 Bern, Switzerland. [Vaz, Michelle] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD 21237 USA. [Zannini, Mariastella; de Cristofaro, Tiziana] CNR Natl Res Council, Inst Expt Endocrinol & Oncol IEOS, I-80131 Naples, Italy. [Frietze, Seth; Farnham, Peggy J.] Univ So Calif, Dept Biochem & Mol Biol, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA. [Eijkelenboom, Astrid] Univ Utrecht, Dept Mol Canc Res, Univ Med Ctr Utrecht, NL-3584 CG Utrecht, Netherlands. [Brown, Philip J.] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Div Med Sci, Oxford OX3 9DU, Oxon, England. [Laperriere, David] Univ Montreal, Mol Targeting Breast Canc Res Unit, Inst Res Immunol & Canc, Montreal, PQ H3T 1J4, Canada. [Leprince, Dominique; Boulay, Gaylor] Inst Pasteur, Ctr Natl Rech Sci CNRS UMR 8161, Inst Biol Lille, F-59021 Lille, Nord Pas De Cal, France. [Prince, Kelly L.; Colvin, Stephanie C.] Indiana Univ Purdue Univ, Dept Cellular & Integrat Physiol, Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Putker, Marrit] Univ Utrecht, Univ Med Ctr Utrecht, Dept Physiol Chem, NL-3584 CG Utrecht, Netherlands. [del Peso, Luis] Univ Autonoma Madrid, Dept Biochem, Sch Med, Madrid 28029, Spain. [Camenisch, Gieri; Wenger, Roland H.] Univ Zurich, Inst Physiol, Zurich Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland. [Mikula, Michal; Ostrowski, Jerzy] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Oncol Genet, Med Ctr Postgrad Educ, PL-02781 Warsaw, Mazovia, Poland. [Rozendaal, Marieke] Univ Montreal, Dept Biochem, Inst Res Immunol & Canc, Stn Ctr Ville, Montreal, PQ H3C 3J7, Canada. [Mader, Sylvie] Univ Montreal, Dept Biochem, Inst Res Immunol & Canc, Montreal, PQ H3T 1J4, Canada. [Rhodes, Simon J.] Indiana Univ Purdue Univ, Dept Biol, Sch Sci, Indianapolis, IN 46202 USA. [Van Rechem, Capucine] Harvard Univ, Sch Med, Dept Med, Canc Ctr,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Olechnowicz, Sam W. Z.] Univ Adelaide, Dept Biochem, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia. [Breslin, Mary B.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat & Biochem & Mol Biol, Res Inst Children,Childrens Hosp New Orleans, New Orleans, LA 70118 USA. [Lan, Michael S.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Res Inst Children,Childrens Hosp New Orleans, New Orleans, LA 70118 USA. [Lan, Michael S.] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, Res Inst Children,Childrens Hosp New Orleans, New Orleans, LA 70118 USA. [Nanan, Kyster K.; LeBrun, David P.] Queens Univ, Dept Pathol & Mol Med, Queens Canc Res Inst, Kingston, ON K7L 3N6, Canada. [Wegner, Michael] Univ Erlangen Nurnberg, Sch Med, Inst Fuer Biochem, Emil Fischer Zentrum, D-91096 Erlangen, Bavaria, Germany. [Mullen, Rachel D.] Indiana Univ Purdue Univ, Dept Mol Biol & Biochem, Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Noy, Peter John] Univ Birmingham, Dept Immun & Infect, Sch Med & Dent Sci, Birmingham B15 2TT, W Midlands, England. [Webb, Carol F.] Oklahoma Med Res Fdn, Immunobiol & Canc Program, Oklahoma City, OK 73104 USA. [Witek, Matthew E.] Jefferson Univ Hosp, Dept Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA. [Ferrell, Scott] Univ Oklahoma, Dept Microbiol & Immunol, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Daniel, Juliet M.] McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. [Waldman, Scott A.] Thomas Jefferson Univ, Dept Pharmacol & Expt Therapeut, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Peet, Daniel J.] Univ Adelaide, Discipline Biochem, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia. [Taggart, Michael; Europe-Finner, G. Nicholas] Newcastle Univ, Inst Cellular Med, Fac Med, Sch Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Jayaraman, Padma-Sheela] Univ Birmingham, Dept Immun & Immunol, Sch Med & Dent Sci, Birmingham B15 2TT, W Midlands, England. [Karrich, Julien J.; Blom, Bianca] Univ Amsterdam, Dept Cell Biol & Histol, Ctr Immunol Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Noord Holland, Netherlands. [Vesuna, Farhad] Johns Hopkins Univ, Div Canc Imaging Res, Dept Radiol, Sch Med, Baltimore, MD 21205 USA. [O'Geen, Henriette] Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. [Sun, Yunfu] Univ Calif San Diego, San Diego, CA 92093 USA. [Gronostajski, Richard M.] SUNY Buffalo, Ctr Excellence Bioinformat & Life Sci, Dept Biochem, Buffalo, NY 14203 USA. [Gronostajski, Richard M.] SUNY Buffalo, Ctr Excellence Bioinformat & Life Sci, Dev Genom Grp, Buffalo, NY 14203 USA. [Woodcroft, Mark W.] Queens Univ, Dept Pathol & Mol Med, Queens Canc Res Inst, Kingston, ON K7K 4G4, Canada. [Hough, Margaret R.] Univ Toronto, Dept Mol & Cellular Biol, Dept Lab Med & Pathobiol, Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Karolczak-Bayatti, Magdalena] Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Bailey, Jarrod] Newcastle Univ, Sch Med, Inst Cellular Med, Fac Med Sci, Newcastle Upon Tyne NE2 4AA, Tyne & Wear, England. [Hankinson, Oliver] Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Biswal, Shyam; Harvey, Christopher J.] Johns Hopkins Univ, Dept Environm Hlth Sci, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [DeBruyne, Jason P.] Morehouse Sch Med, Dept Pharmacol & Toxicol, Neurosci Inst, Atlanta, GA 30310 USA. [Hogenesch, John B.] Univ Penn, Dept Pharmacol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Hevner, Robert F.] Univ Washington, Dept Neurol Surg, Seattle Childrens Res Inst, Seattle, WA 98101 USA. [Heligon, Christophe] Univ Lausanne, Fac Biol & Med, Ctr Integrated Genom, CH-1015 Lausanne, Vaud, Switzerland. [Luo, Xin M.] Virginia Polytech Inst & State Univ, Dept Biomed Sci & Pathobiol, VA MD Reg Coll Vet Med, Blacksburg, VA 24061 USA. [Millen, Kathleen Joyce; Mishima, Yuriko] Univ Washington, Ctr Integrat Brain Res, Seattle Childrens Res Inst, Seattle, WA 98101 USA. [Blank, Marissa Cathleen] Univ Illinois, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. [Sharlin, David S.; Forrest, Douglas] Natl Inst Diabet Digest & Kidney Disorders, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Dahlman-Wright, Karin; Zhao, Chunyan] Karolinska Inst, Dept Biosci & Nutr, Novum, SE-14183 Stockholm, Sweden. [Sinha, Satrajit; Chakrabarti, Rumela] SUNY Buffalo, Dept Biochem, Sch Med & Biomed Sci, Buffalo, NY 14203 USA. RP Wasserman, WW (reprint author), Univ British Columbia, Dept Med Genet, Ctr Mol Med & Therapeut, Fac Med,Child & Family Res Inst, 950 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. EM wyeth@cmmt.ubc.ca RI Vesuna, Farhad/G-3179-2010; Mikula, Michal/G-8276-2011; Marco-Ferreres, Raquel/J-7122-2012; Wenger, Roland/B-7953-2009; Kist, Ralf/B-4982-2008; Ramos, Oscar/E-1862-2013; Banham, Alison/B-2966-2009; Benayoun, Berenice/K-7048-2012; del Peso, Luis/K-9391-2014; Zannini, Mariastella/I-1735-2012; Wasserman, Wyeth/I-4866-2015; de Leeuw, Charles/G-2939-2012; Luo, Xin/J-6544-2016; OI Banham, Alison/0000-0002-3197-273X; Vesuna, Farhad/0000-0002-0356-5096; Noy, Peter/0000-0001-6142-8957; Olechnowicz, Sam/0000-0001-7879-7708; Taggart, Michael/0000-0002-9981-2783; Farnham, Peggy/0000-0003-4469-7914; Cheung, Warren/0000-0003-0267-7464; Grontved, Lars/0000-0002-6735-8483; Brosens, Jan/0000-0003-0116-9329; DeBruyne, Jason/0000-0001-9803-9568; Mikula, Michal/0000-0003-3447-7328; Wenger, Roland/0000-0001-7592-4839; Kist, Ralf/0000-0003-3729-5693; Ramos, Oscar/0000-0002-5788-4500; Benayoun, Berenice/0000-0002-7401-4777; del Peso, Luis/0000-0003-4014-5688; de Leeuw, Charles/0000-0001-9413-2095; Luo, Xin/0000-0002-2809-5836; Mandrup, Susanne/0000-0002-0961-5787; Wasserman, Wyeth/0000-0001-6098-6412; Portales-Casamar, Elodie/0000-0002-9998-7858; Tschan, Mario P./0000-0001-5897-3647; Wegner, Michael/0000-0002-4586-3294; Hoodless, Pamela/0000-0003-1371-0725 FU Pleiades Promoter project; Genome Canada; Genome British Columbia; GlaxoSmithKline RD Limited; British Columbia Mental Health and Addiction Services; Child and Family Research Institute; University of British Columbia Institute of Mental Health; University of British Columbia Office of the Vice President Research; National Institutes of Health [R01GM084875, CA45250, 1U54HG004558, GM007377, U01 ES017154, R01 HD42024, 044215, CA75123, CA95026, CA146033, NIH/NIAID R01-AI080564-01, GM079239, HL081205, R01 MH058869, R01GM069417, R01 GM088277-01]; Gene Regulation Bioinformatics Laboratory; Canada Foundation for Innovation (CFI); University of British Columbia Work Study Program; Faculty of Medicine of the University of British Columbia; National Sciences and Engineering Research Council of Canada; Michael Smith Foundation for Health Research (MSFHR); Canadian Institutes of Health Research/MSFHR Strategic Program in Bioinformatics; Canadian Institutes of Health Research (CIHR) Frederick Banting; Charles Best Canada Graduate Scholarship Doctoral Award; MSFHR Graduate Doctoral Scholarship award; CHAARM in Europe; INSERM; EFSD; ANR; CIHR CGS-M Graduate Award; MSFHR Junior Graduate Scholarship; Canadian Institutes of Health Research; Sharon Stewart Trust; Deutsche Forschungsgemeinschaft; Cancer Research UK; Breast Cancer Campaign; Faculty of Medical Sciences, Newcastle University; BBSRC; Novartis; Ministerio de Economia y Competitividad (MEyC) in Spain; CAM; Biomedical Research Unit in Reproductive Health; University Hospitals Coventry; Warwickshire NHS Trust; private foundation Fundaluce; private foundation ONCE; private foundation Retina Espana; AMN; Universite Paris Diderot-Paris 7; Danish Natural Science Research Council; Centre national de la recherche scientifique (CNRS); Universite Paris-Diderot; Association pour la recherche contre le cancer (ARC); Fondation pour la recherche medicale (FRM); Institut Universitaire de France (IUF); MSFHR; Canadian Institutes for Health Research; Leukaemia and Lymphoma Research and Cancer Research UK; National Institutes of Health (NIH) [ES11863, ES018998, HL66109, K08 CA120349, ES11893, HL 66109, F32HD068113, R01DK061436, R01CA28868, T32GM007183, R01NS050386, R01NS044262, R01 DK053892, R21 MH087397]; CIHR; Heart and Stroke Foundation of Canada; National Institute for General Medical Sciences; Nebraska Department of Health; National Cancer Institute; Italian Association for Cancer Research (AIRC); Italian Ministry of Education, University and Research (MIUR-PRIN); Leukaemia and Lymphoma Research; NIH [HD42024, 5RO1 CA097226-03, R01 NS050386]; Spanish Ministry of Science and Innovation; 7th Framework research Program of the European Union; EU FP7; Swiss National Science Foundation [31003A_129962/1]; Ministry of Science and Higher Education [IP 2010 026770, N N401 071439]; Montreal Center for Experimental Therapeutics in Cancer; Canadian Institutes for Health Research [MOP 13-147]; Faculte des Etudes Superieures at Universite de Montreal; Research Institute for Children, Children's Hospital New Orleans, LA; Research Institute at Children's Hospital, New Orleans; Canadian Institutes of Health Research [MOP-84320]; Fonds der Chemischen Industrie; CIHR [MOP-84320, MOP-89806]; Department of Medical and Dental Sciences, University of Birmingham; Oklahoma Center for Adult Stem Cell Research; Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN/238700-2010]; Australian Research Council; National Health and Medical Research Council of Australia; Welcome Trust and Breast Cancer Campaign; Dutch Organization for Medical Research (ZonMW); Netherlands organization for health research and development ZonMW [VIDI-917-66-310]; Landsteiner foundation [0608]; National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH); New York State Stem Cell Science (NYSTEM); Cancer Research Society; Dina Gordon-Malkin Ontario Graduate Scholarship in Science and Technology; Medical Research Council (MRC) in the United Kingdom; British Heart Foundation; Wellcome Trust; Action Medical Research; Medical Research Council (MRC) in the United Kingdom [G0800202]; Leukemia and Lymphoma Society of Canada; National Heart, Lung, and Blood Institute Specialized Centers of Clinically Oriented Research [P50HL084945]; Center for Childhood Asthma in the Urban Environment [P50ES015903]; National Institute on Environmental Health Sciences Center [P30 ES003819]; Clinical Innovator Award from the Flight Attendant Medical Research Institute; NIEHS [ES07141]; Swedish Medical Research Council; Swedish Cancer Foundation; Novo Nordisk Foundation; Swedish Cancer Society (Cancerfonden) [CAN 2007/1113]; Fred Hutchinson Cancer Research Center (FHCRC); [T32]; [HL091219]; [R24 EY017540] FX We thank all authors who have made this project possible, especially our alpha and beta testers who have worked closely with us to refine the contents and user interface of this resource. We thank David J Arenillas, and Miroslav Hatas for providing programming assistance and systems administration support. We highlight author Frances M Sladek (University of California, Riverside) for extensive suggestions about the system interface and contents. We thank Frederick Pio (Simon Fraser University) for early assistance with TF structural modeling. TFe was supported by the Pleiades Promoter project, which is funded by Genome Canada, Genome British Columbia, GlaxoSmithKline R&D Limited, the British Columbia Mental Health and Addiction Services, Child and Family Research Institute, the University of British Columbia Institute of Mental Health, and the University of British Columbia Office of the Vice President Research. It is now supported by funding from the National Institutes of Health (grant no. R01GM084875 to WWW). Computer hardware resources utilized in this project were supported by the Gene Regulation Bioinformatics Laboratory funded by the Canada Foundation for Innovation (CFI). We sincerely thank the multitude of funding agencies throughout the world that have turned this project into reality. Here are our funding acknowledgments. DY is supported by funding from the University of British Columbia Work Study Program as well as the Faculty of Medicine of the University of British Columbia. EB is funded by T32 training grant. WAC is funded by the National Sciences and Engineering Research Council of Canada, the Michael Smith Foundation for Health Research (MSFHR) and the Canadian Institutes of Health Research/MSFHR Strategic Program in Bioinformatics. DLF is supported by a Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship Doctoral Award and MSFHR Graduate Doctoral Scholarship award. OHPR is funded by CHAARM in Europe. MVC is funded by INSERM, EFSD, and ANR. CNdL is funded by a CIHR CGS-M Graduate Award and a MSFHR Junior Graduate Scholarship. EMS is currently funded by Canadian Institutes of Health Research, Sharon Stewart Trust, and Genome British Columbia. GUR's work is supported by funding from Deutsche Forschungsgemeinschaft. EWFL's work is supported by Cancer Research UK and Breast Cancer Campaign. RK was funded by a research fellowship of the Faculty of Medical Sciences, Newcastle University. MSW is funded by a CASE Studentship from the BBSRC in partnership with Novartis. RMF's work is supported by funding from Ministerio de Economia y Competitividad (MEyC) in Spain, CAM, and private foundations Fundaluce, ONCE, and Retina Espana. JJB is funded by the Biomedical Research Unit in Reproductive Health, University Hospitals Coventry and Warwickshire NHS Trust. LLB's work is supported by funding from Ministerio de Economia y Competitividad (MEyC) in Spain, CAM, and private foundations Fundaluce, ONCE, and Retina Espana. PB's work is supported by funding from Ministerio de Economia y Competitividad (MEyC) in Spain, CAM, and private foundations Fundaluce, ONCE, and Retina Espana. BAB was supported by an AMN and Universite Paris Diderot-Paris 7 PhD fellowship. LG is funded by the Danish Natural Science Research Council. SuM is funded by the Danish Natural Science Research Council.; RAV's laboratory is funded by the Centre national de la recherche scientifique (CNRS), Universite Paris-Diderot, Association pour la recherche contre le cancer (ARC), Fondation pour la recherche medicale (FRM), and Institut Universitaire de France (IUF). PAH is supported by funding from the MSFHR, Genome Canada, Genome British Columbia and Canadian Institutes for Health Research. BET is funded by grants number HL091219 and R24 EY017540. AHB is funded by Leukaemia and Lymphoma Research and Cancer Research UK. SPR is funded by the National Institutes of Health (NIH) grants ES11863, ES018998 and HL66109. RLC is funded by CIHR and the Heart and Stroke Foundation of Canada. ML is funded by the National Institutes of Health (NIH) grant K08 CA120349. MV is funded by the National Institutes of Health (NIH) grants ES11893 and HL 66109. AR is funded by the National Institute for General Medical Sciences, Nebraska Department of Health and the National Cancer Institute. MZ is funded by the Italian Association for Cancer Research (AIRC) and the Italian Ministry of Education, University and Research (MIUR-PRIN). SF is funded by the National Institutes of Health (grants CA45250, 1U54HG004558, GM007377). PJF is funded by the National Institutes of Health (grants CA45250, 1U54HG004558, and U01 ES017154). PJB is funded by Leukaemia and Lymphoma Research. KLP is funded by the National Institutes of Health (NIH) grant F32HD068113, and SJR is funded by NIH grant HD42024. LdP is funded by the Spanish Ministry of Science and Innovation, as well as the 7th Framework research Program of the European Union. RHW is funded by the EU FP7 and the Swiss National Science Foundation (grant 31003A_129962/1). MM is supported by the Ministry of Science and Higher Education (grant IP 2010 026770). MR was supported by studentships from the Faculte des Etudes Superieures at Universite de Montreal and from the Montreal Center for Experimental Therapeutics in Cancer. SyM is funded by the Canadian Institutes for Health Research (grant MOP 13-147) and holds the CIBC Breast Cancer Research Chair at Universite de Montreal. JO is supported by the Ministry of Science and Higher Education (grant N N401 071439) SJR is funded by the National Institutes of Health grant R01 HD42024. MBB is funded by the Research Institute for Children, Children's Hospital New Orleans, LA. MBB performed this work in collaboration with the Diana Helis Henry Medical Research Foundation. MSL is funded by the Research Institute at Children's Hospital, New Orleans, and the National Institutes of Health (NIH) grant R01DK061436. KKN and JMD are funded by Canadian Institutes of Health Research (grant MOP-84320). MW is funded by Deutsche Forschungsgemeinschaft and Fonds der Chemischen Industrie. JH is funded by CIHR (grant MOP-89806). PN is funded by the Department of Medical and Dental Sciences, University of Birmingham. CFW is funded by the National Institutes of Health (grant 044215) and the Oklahoma Center for Adult Stem Cell Research. JMD is supported by funding from the CIHR (grant MOP-84320) and the Natural Sciences and Engineering Research Council of Canada (NSERC grant RGPIN/238700-2010). SW is funded by the National Institutes of Health grants CA75123, CA95026, and CA146033. DJP is funded by Australian Research Council and the National Health and Medical Research Council of Australia PSJ is funded by the Welcome Trust and Breast Cancer Campaign. JJK is funded by the Dutch Organization for Medical Research (ZonMW).; BB is funded by the Netherlands organization for health research and development ZonMW (grant VIDI-917-66-310), the Landsteiner foundation (grant 0608), and the National Institutes of Health (grant NIH/NIAID R01-AI080564-01). RMG is supported by funding from the National Heart, Lung and Blood Institute (NHLBI) at the National Institutes of Health (NIH), and New York State Stem Cell Science (NYSTEM). MWW is a recipient of a Doctoral Award from the Canadian Institutes of Health Research. MRH is funded by the Canadian Institutes of Health Research and the Cancer Research Society. EC is funded by the Dina Gordon-Malkin Ontario Graduate Scholarship in Science and Technology. GNEF have been supported by funding from the Medical Research Council (MRC) in the United Kingdom, the British Heart Foundation, the Wellcome Trust, and Action Medical Research. MKB is funded by the Medical Research Council (MRC) in the United Kingdom, grant G0800202. OH is funded by the National Institutes of Health (NIH) grant R01CA28868. VR is funded by the NIH grant 5RO1 CA097226-03. DPL is funded by the Canadian Institutes of Health Research, Cancer Research Society, and the Leukemia and Lymphoma Society of Canada. SB is funded by the National Institutes of Health grants GM079239 and HL081205, National Heart, Lung, and Blood Institute Specialized Centers of Clinically Oriented Research grant P50HL084945, Center for Childhood Asthma in the Urban Environment grant P50ES015903, National Institute on Environmental Health Sciences Center grant P30 ES003819, and a Clinical Innovator Award from the Flight Attendant Medical Research Institute. CJH is funded by NIEHS grant ES07141. RFH is funded by the National Institutes of Health (grant R01 MH058869). MCB was funded by National Institutes of Health (NIH) training grant T32GM007183 and also by the NIH grant R01 NS050386 (through KJM). KJM is funded by the National Institutes of Health (grants R01NS050386, R01NS044262). KD is funded by the Swedish Medical Research Council, the Swedish Cancer Foundation, and the Novo Nordisk Foundation. CZ's work was supported by grants from the Swedish Cancer Society (Cancerfonden), grant CAN 2007/1113. SS is funded by the National Institutes of Health (grant R01GM069417). FMS is funded by the National Institutes of Health (NIH) grants R01 DK053892 and R21 MH087397. PHB is funded by a new development funding from the Fred Hutchinson Cancer Research Center (FHCRC) and the National Institutes of Health (grant no. R01 GM088277-01). NR 40 TC 34 Z9 34 U1 1 U2 23 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 3 AR R24 DI 10.1186/gb-2012-13-3-r24 PG 25 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002PL UT WOS:000308544200009 PM 22458515 ER PT J AU Wozniak, J Gonenc, A Biederman, J Moore, C Joshi, G Georgiopoulos, A Hammerness, P McKillop, H Lukas, SE Henin, A AF Wozniak, Janet Goenenc, Atilla Biederman, Joseph Moore, Constance Joshi, Gagan Georgiopoulos, Anna Hammerness, Paul McKillop, Hannah Lukas, Scott E. Henin, Aude TI A Magnetic Resonance Spectroscopy Study of the Anterior Cingulate Cortex In Youth with Emotional Dysregulation SO ISRAEL JOURNAL OF PSYCHIATRY AND RELATED SCIENCES LA English DT Article ID PEDIATRIC BIPOLAR DISORDER; CHILD-BEHAVIOR CHECKLIST; SUBGENUAL PREFRONTAL CORTEX; MOOD DISORDERS; GLUTAMATE NEUROTRANSMISSION; RATING-SCALE; FRONTAL-LOBE; CBCL; PHENOTYPE; MANIA AB Background: The main aim of this study was to use proton Magnetic Resonance Spectroscopy (MRS) to identify brain biomarkers for emotional dysregulation in youth as measured by subscales of the Child Behavior Checklist (CBCL). Methods: We measured glutamate (Glu) concentrations in the anterior cingulated cortex (ACC) of 37 pediatric subjects (aged 6-17 years) using high field (4.0 Tesla) proton Magnetic Resonance Spectroscopy (MRS). Subjects were grouped based on combined T scores on three subscales (Anxiety/Depression, Aggression and Attention) of the CBCL previously associated with deficits in the regulation of emotion. Subjects were stratified into those with high (>180) (N=10) and low (<180) (N=27) scores. Limitations: Limitations include small sample size, wide age range studied, focus on Anterior Cingulate Cortex (ACC) only, and that some subjects received psychopharmacological treatments. Results: We found a statistically significant correlation between Glu levels in the ACC and CBCL dysregulation profile scores among subjects with high dysregulation profile scores. Conclusions: These results suggest that glutamatergic dysregulation in the ACC may represent a useful bio-marker of emotional dysregulation in youth. Further investigation into the causality, time line and utility as a predictive metric is warranted. C1 [Wozniak, Janet] Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Goenenc, Atilla; Lukas, Scott E.] McLean Hosp, Neuroimaging Ctr, Belmont, MA 02178 USA. [Wozniak, Janet; Goenenc, Atilla; Biederman, Joseph; Joshi, Gagan; Georgiopoulos, Anna; Hammerness, Paul; Lukas, Scott E.; Henin, Aude] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Moore, Constance] Univ Massachusetts, Worcester, MA 01605 USA. RP Wozniak, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, 15 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM jwozniak@partners.org FU National Institutes of Health (NIH) [K08MH001503, R01MH066237]; Susan G. Berk Endowed Fund for Juvenile Bipolar Disorder; Heinz C. Prechter Bipolar Research Fund; NARSAD Young Investigator Award; SHINE Initiative; Massachusetts General Hospital Claflin Distinguished Scholars Award; [MH073998] FX This study was funded, in part, by National Institutes of Health (NIH) grants K08MH001503 and R01MH066237 to Dr. Wozniak, the Susan G. Berk Endowed Fund for Juvenile Bipolar Disorder, the Heinz C. Prechter Bipolar Research Fund, and the support of members of the MGH Pediatric Psychopharmacology Council. In addition this work was supported by a NARSAD Young Investigator Award in collaboration with a donation from the SHINE Initiative (Henin), and a Massachusetts General Hospital Claflin Distinguished Scholars Award to Dr. Henin. This study was also funded in part by MH073998 to Dr. Moore. We would like to acknowledge Dave Crowley, BA, Caroline Rycyna, BA, and Laura Rindlaub for their contributions to the study. NR 65 TC 6 Z9 7 U1 5 U2 9 PU MEDIAFARM GROUP PI TEL-AVIV PA 23 ZAMENHOFF ST, TEL-AVIV, 64373, ISRAEL SN 0333-7308 J9 ISR J PSYCHIATR REL JI Isr. J. Psychiatr. Relat. Sci. PY 2012 VL 49 IS 1 BP 62 EP 69 PN 1 PG 8 WC Psychiatry SC Psychiatry GA 004RA UT WOS:000308697600007 PM 22652930 ER PT J AU Ginde, AA Wolfe, P Camargo, CA Schwartz, RS AF Ginde, A. A. Wolfe, P. Camargo, C. A., Jr. Schwartz, R. S. TI Defining vitamin D status by secondary hyperparathyroidism in the U.S. population SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE Epidemiology; hyperparathyroidism; hypovitaminosis D; parathyroid hormone; vitamin D ID SERUM PARATHYROID-HORMONE; 25-HYDROXYVITAMIN D LEVEL; BONE-MINERAL DENSITY; D DEFICIENCY; D INSUFFICIENCY; CARDIOVASCULAR-DISEASE; CALCIUM-ABSORPTION; HYPOVITAMINOSIS D; REFERENCE RANGE; BLOOD-PRESSURE AB Background: Vitamin D is associated with a variety of health outcomes, but the exact definition of vitamin D sufficiency remains controversial. Aim: We sought to define skeletal-related vitamin D sufficiency by estimating maximum PTH suppression in the U.S. population. Methods: We performed a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES), 2003-2006. We examined the association between serum 25-hydroxyvitamin D (25OHD) level and serum PTH level in 14,681 participants aged >= 6 yr. We also evaluated the 25OHD-PTH association using 2 thresholds of hyperparathyroidism: PTH >= 45 pg/ml and >= 75 pg/ml. Results: The mean 25OHD level was 24 ng/ml and mean PTH was 42 pg/ml. PTH >= 45 pg/ml was present in 35% of the population, while PTH >= 75 pg/ml was present in 7%. The prevalence of 25OHD levels <40 ng/ml and <30 ng/ml was 95% and 77%, respectively. In both unadjusted and adjusted models, there was a strong inverse relationship between 25OHD and PTH. Compared to 25OHD >= 40 ng/ml, the 25OHD-PTH association was 2.36 [95% confidence interval (CI), 2.08-2.671 times greater for 25OHD<5 ng/ml and 1.12 (95%CI, 1.07-1.17) times greater for 25OHD 30-39.9 ng/ml. Compared to 25OHD >= 40 ng/ml, 25OHD levels of 20-29.9 ng/ml [odds ratio (OR) 2.0 (95%CI, 1.4-2.8)] but not 30-39.9 ng/ml [OR 1.1 (95%CI, 0.8-1.6)] were independently associated with PTH >= 45 pg/ml. Conclusions: Optimal vitamin D status, defined by estimated maximum PTH suppression, does not occur until at least 25OHD levels >= 40 ng/ml. Using these thresholds, most of the U.S. population needs more vitamin D. Large, prospective studies are needed to determine optimal vitamin D supplementation. (J. Endocrinol. Invest. 35: 42-48, 2012) (C)2012, Editrice Kurds C1 [Ginde, A. A.] Univ Colorado, Denver Sch Med, Dept Emergency Med, Aurora, CO 80045 USA. [Wolfe, P.] Colorado Sch Publ Hlth, Dept Biostat & Informat, Aurora, CO USA. [Camargo, C. A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Schwartz, R. S.] Univ Colorado, Denver Sch Med, Div Geriatr Med, Aurora, CO 80045 USA. RP Ginde, AA (reprint author), Univ Colorado, Denver Sch Med, Dept Emergency Med, 12401 E 17th Ave,B-215, Aurora, CO 80045 USA. EM adit.ginde@ucdenver.edu FU Massachusetts General Hospital Center for D-receptor Activation Research (Boston, MA); NIH [KL2 RR025779, R01 AG019339, R01 AG028746] FX This study was funded by a competitive investigator-initiated grant from the Massachusetts General Hospital Center for D-receptor Activation Research (Boston, MA). Dr. Ginde was supported by NIH grant KL2 RR025779. Dr. Schwartz was supported by NIH grants R01 AG019339 and R01 AG028746. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 48 TC 24 Z9 24 U1 1 U2 8 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD JAN PY 2012 VL 35 IS 1 BP 42 EP 48 DI 10.3275/7742 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 995WL UT WOS:000308045300011 PM 21606669 ER PT J AU Cortez-Retamozo, V Etzrodt, M Pittet, MJ AF Cortez-Retamozo, Virna Etzrodt, Martin Pittet, Mikael J. TI Regulation of Macrophage and Dendritic Cell Responses by Their Lineage Precursors SO JOURNAL OF INNATE IMMUNITY LA English DT Review DE Host defense; Immune response; Mononuclear phagocyte system ID BLOOD MONOCYTE SUBSETS; HEMATOPOIETIC STEM-CELL; STEADY-STATE CONDITIONS; IN-VIVO; LANGERHANS CELLS; BONE-MARROW; INFLAMMATORY MONOCYTES; MYOCARDIAL-INFARCTION; ALVEOLAR MACROPHAGES; T-CELLS AB Tissue macrophages (Mo) and dendritic cells (DC) are thought to derive from hematopoietic stem cells, which exist in the bone marrow and generate intermediate precursor populations with increasingly restricted lineage potentials. There exists several precursors committed to the M and DC lineages; these cells exhibit distinct tropism and function and respond differentially in pathophysiologic conditions. In this review, we consider experimental contexts in which Mo and DC responses in tissue are not only dictated by the local environment, but also by the quantity and quality of newly recruited lineage precursor cells. Consequently, we discuss whether therapeutic control of Mo and DC responses in tissue may be achieved through manipulation of their lineage precursors. Copyright (C) 2012 S. Karger AG, Basel C1 [Pittet, Mikael J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pittet, MJ (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu RI Etzrodt, Martin/P-3325-2015 OI Etzrodt, Martin/0000-0003-1928-3904 FU Boehringer Ingelheim Fonds; AACR; National Institutes of Health [R01-AI084880, P50-CA086355, N01-HV08235/HHSN268201000044C] FX M.E. is part of the International PhD program 'Cancer and Immunology' at the University of Lausanne, Switzerland, and supported by a PhD fellowship from the Boehringer Ingelheim Fonds and an AACR Centennial Pre-Doctoral Fellowship in Cancer Research. The work of M.J.P. is supported by the National Institutes of Health grants R01-AI084880, P50-CA086355 and N01-HV08235/HHSN268201000044C. NR 115 TC 9 Z9 10 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X J9 J INNATE IMMUN JI J. Innate Immun. PY 2012 VL 4 IS 5-6 BP 411 EP 423 DI 10.1159/000335733 PG 13 WC Immunology SC Immunology GA 002ZA UT WOS:000308576400002 PM 22433183 ER PT J AU Armento, MEA Stanley, MA Marsh, L Kunik, ME York, MK Bush, AL Calleo, JS AF Armento, Maria E. A. Stanley, Melinda A. Marsh, Laura Kunik, Mark E. York, Michele K. Bush, Amber L. Calleo, Jessica S. TI Cognitive Behavioral Therapy for Depression and Anxiety in Parkinson's Disease: A Clinical Review SO JOURNAL OF PARKINSONS DISEASE LA English DT Review DE Parkinson's disease; depression; anxiety; CBT ID QUALITY-OF-LIFE; CONTROLLED-TRIAL; NONMOTOR SYMPTOMS; MAJOR DEPRESSION; DOUBLE-BLIND; PREVALENCE; DISABILITY; FEASIBILITY; ANTIDEPRESSANTS; INTERVENTION AB Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is generally defined by its progressive motor features; but increased attention is being paid to its non-motor neuropsychiatric symptoms, which profoundly impact quality of life for patients and caregivers. Anxiety and depression are particularly problematic and are the strongest predictors of quality of life in PD. Recent research has focused on non-pharmacological approaches to treating depression and anxiety in patients with PD. Cognitive-behavioral therapy (CBT) is a potentially efficacious non-pharmacological treatment for mood and anxiety symptoms associated with PD. Accordingly, this review examines empirical studies of CBT-based treatments for depression and anxiety symptoms in PD. Medical Subject Headings were used in searches of PsychInfo and PubMed of English-language articles published in peer-reviewed journals, resulting in the identification of 10 articles. Four additional articles were identified from the references of these articles and upon the suggestions of experts, for 15 articles in all. Results of individual studies varied significantly; however, the randomized controlled trials showed encouraging results and support the need for further investigation of the utility of CBT for depressed and anxious patients with PD. CBT is potentially a useful treatment for patients with PD and comorbid depression and/or anxiety, but more systematic research will be necessary to measure its effects. C1 [Armento, Maria E. A.; Stanley, Melinda A.; Kunik, Mark E.; Bush, Amber L.; Calleo, Jessica S.] Michael E DeBakey VA Med Ctr, Houston VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [Armento, Maria E. A.; Stanley, Melinda A.; Marsh, Laura; Kunik, Mark E.; Bush, Amber L.; Calleo, Jessica S.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Marsh, Laura; York, Michele K.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Armento, Maria E. A.; Stanley, Melinda A.; Kunik, Mark E.] VA S Cent Mental Illness Res Educ & Clin Ctr MIRE, Houston, TX USA. [York, Michele K.] Parkinsons Dis Res Educ & Clin Ctr PADRECC, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Marsh, Laura; Calleo, Jessica S.] Michael E DeBakey Vet Affairs Med Ctr Mental Hlth, Houston, TX USA. RP Armento, MEA (reprint author), Hlth Serv Res & Dev Ctr Excellence, 2002 Holcombe Blvd,MEDVAMC 152, Houston, TX 77030 USA. EM armento@bcm.edu FU VA HSR&D Houston Center of Excellence [HFP90-020]; Michael E. DeBakey Veterans Affairs Medical Center; National Institute of Mental Health (NIMH) [RO1-MH069666]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This work is the result of work supported with resources and the use of facilities at the VA HSR&D Houston Center of Excellence (HFP90-020) at the Michael E. DeBakey Veterans Affairs Medical Center and National Institute of Mental Health (NIMH grant RO1-MH069666 to ALB and LM). The views expressed reflect those of the authors and not necessarily those of the NIMH, National Institutes of Health, Department of Veterans Affairs or Baylor College of Medicine. The NIMH had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. The authors report no financial conflicts of interest.; This work is the result of work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and the VA HSR&D Houston Center of Excellence (HFP90-020). The views expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs, the US government or Baylor College of Medicine. NR 89 TC 15 Z9 15 U1 4 U2 30 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2012 VL 2 IS 2 BP 135 EP 151 DI 10.3233/JPD-2012-12080 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 001UM UT WOS:000308485600007 PM 23939438 ER PT J AU Palacios, N Gao, X Schwarzschild, M Ascherio, A AF Palacios, Natalia Gao, Xiang Schwarzschild, Michael Ascherio, Alberto TI Declining Quality of Life in Parkinson Disease Before and After Diagnosis SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Parkinson; progression; epidemiology; quality of life ID HEALTH; WOMEN; WEIGHT; QUESTIONNAIRE; DISABILITY; FREQUENCY; RISK AB We sought to assess the quality of life in PD patients before the diagnosis, in comparison to age-matched individuals free of PD, among participants in two large prospective cohorts of men and women. Components of the Short-Form Health Status Survey (SF36) were administered to all participants in 1996 and 2008 in the Health Professionals Follow-up Study (HPFS), and in 1992, 1996, 2000 and 2004 in the Nurses' Health Study (NHS). We used scores in 7 health-related quality of life-dimensions, that were rated from 1(worst) to 100(best) points. We fitted a multivariate mixed-effect model with repeated measures to estimate the expected decline with age and compared that to the decline observed among PD cases by time to diagnosis. 454 men and 414 women with PD contributed data to the analyses. A decline in physical function in PD patients relative to the whole cohort began approximately 7.5 years prior to diagnosis in women and 3 years prior to diagnosis in men, and continued to decline thereafter with a rate of 2.35 and 1.43 points per year in women and men respectively (p < 0.001 for both). For comparison, the average yearly decline in individuals without PD was 0.42 and 0.23 points per year in women and men respectively. Other measures of quality of life (only available in women) declined in a similar pattern to physical function. In summary, the quality of life in PD patients begins to decline years before the diagnosis. C1 [Palacios, Natalia; Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Schwarzschild, Michael] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Palacios, N (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM palacios@hsph.harvard.edu FU NIEHS [K01 ES019183-01]; NIH [R01 NS061858]; US Government (DoD/NETPR); US Government (NIH) [R01, R21, K24]; Michael J. Fox Foundation; RJG Foundation; American Parkinson Disease Association FX The work in this manuscript was funded by NIEHS K01 ES019183-01 to Dr. Palacios, funding from NIH to Dr Gao, US Government (DoD/NETPR and NIH R01, R21 and K24) and foundations (Michael J. Fox Foundation, RJG Foundation and American Parkinson Disease Association) to Dr. Schwarzschild and NIH R01 NS061858 to Dr. Ascherio. NR 19 TC 4 Z9 5 U1 1 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2012 VL 2 IS 2 BP 153 EP 160 DI 10.3233/JPD-2012-12083 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 001UM UT WOS:000308485600008 PM 23939439 ER PT J AU Verfaellie, M Race, E Keane, MM AF Verfaellie, Mieke Race, Elizabeth Keane, Margaret M. TI MEDIAL TEMPORAL LOBE CONTRIBUTIONS TO FUTURE THINKING: EVIDENCE FROM NEUROIMAGING AND AMNESIA SO PSYCHOLOGICA BELGICA LA English DT Article ID MENTAL TIME-TRAVEL; CONSTRUCTIVE EPISODIC SIMULATION; AUTOBIOGRAPHICAL MEMORY; EVENTS; BRAIN; HIPPOCAMPUS; EXPERIENCES; IMPAIRMENT; ACTIVATION; PATTERNS AB Following early amnesic case reports, there is now considerable evidence suggesting a link between remembering the past and envisioning the future. This link is evident in the overlap in neural substrates as well as cognitive processes involved in both kinds of tasks. While constructing a future narrative requires multiple processes, neuroimaging and lesion data converge on a critical role for the medial temporal lobes (MTL) in retrieving and recombining details from memory in the service of novel simulations. Deficient detail retrieval and recombination may lead to impairments not only in episodic, but also in semantic prospection. MTL contributions to scene construction and mental time travel may further compound impairments in amnesia on tasks that pose additional demands on these processes, but are unlikely to form the core deficit underlying amnesics' cross-domain future thinking impairment. Future studies exploring the role of episodic memory in other forms of self-projection or future-oriented behaviour may elucidate further the adaptive role of memory. C1 [Verfaellie, Mieke; Race, Elizabeth; Keane, Margaret M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Keane, Margaret M.] Wellesley Coll, Dept Psychol, Wellesley, MA 02181 USA. [Verfaellie, Mieke; Race, Elizabeth; Keane, Margaret M.] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. RP Verfaellie, M (reprint author), VA Boston Healthcare Syst, Memory Disorders Res Ctr 151A, 150 S Huntington Ave, Boston, MA 02130 USA. EM verf@bu.edu FU NIMH NIH HHS [R01 MH093431] NR 52 TC 8 Z9 8 U1 1 U2 7 PU BELGIAN PSYCHOL SOC PI LOUVAIN PA TIENSESTRAAT 102, 3000 LOUVAIN, BELGIUM SN 0033-2879 J9 PSYCHOL BELG JI Psychol. Belg. PY 2012 VL 52 IS 2-3 SI SI BP 77 EP 94 PG 18 WC Psychology, Multidisciplinary SC Psychology GA 004XN UT WOS:000308714900002 PM 23447709 ER PT J AU Sakakima, H Khan, M Dhammu, TS Shunmugavel, A Yoshida, Y Singh, I Singh, AK AF Sakakima, Harutoshi Khan, Mushfiquddin Dhammu, Tajinder S. Shunmugavel, Anandakumar Yoshida, Yoshihiro Singh, Inderjit Singh, Avtar K. TI Stimulation of functional recovery via the mechanisms of neurorepair by S-nitrosoglutathione and motor exercise in a rat model of transient cerebral ischemia and reperfusion SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE GSNO; IR; motor exercise; neurorepair; neurobehavior; rehabilitation; S-nitrosylation; stroke ID TRAUMATIC BRAIN-INJURY; SPINAL-CORD-INJURY; NF-KAPPA-B; NITRIC-OXIDE; EXPERIMENTAL STROKE; NEUROVASCULAR UNIT; GLUTATHIONE; ACTIVATION; PATHWAY; NITROSYLATION AB Purpose: Stroke disability stems from insufficient neurorepair mechanisms. Improvement of functions has been achieved through rehabilitation or therapeutic agents. Therefore, we combined exercise with a neurovascular protective agent, S-nitrosoglutathione (GSNO), to accelerate functional recovery. Methods: Stroke was induced by middle cerebral artery occlusion for 60 min followed by reperfusion in adult male rats. Animals were treated with vehicle (IR group), GSNO (0.25 mg/kg, GSNO group), rotarod exercise (EX group) and GSNO plus exercise (GSNO+EX group). The groups were studied for 14 days to determine neurorepair mechanisms and functional recovery. Results: Treated groups showed reduced infarction, decreased neuronal cell death, enhanced neurotrophic factors, and improved neurobehavioral functions. However, the GSNO+EX showed greater functional recovery (p < 0.05) than the GSNO or the EX group. A GSNO sub group, treated 24 hours after IR, still showed motor function recovery (p < 0.001). The protective effect of GSNO or exercise was blocked by the inhibition of Akt activity. Conclusions: GSNO and exercise aid functional recovery by stimulating neurorepair mechanisms. The improvements by GSNO and exercise depend mechanistically on the Akt pathway. A combination of exercise and GSNO shows greater functional recovery. Improved recovery with GSNO, even administered 24 hours post-IR, demonstrates its clinical relevance. C1 [Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Sakakima, Harutoshi; Khan, Mushfiquddin; Dhammu, Tajinder S.; Shunmugavel, Anandakumar; Singh, Inderjit] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Sakakima, Harutoshi; Yoshida, Yoshihiro] Kagoshima Univ, Sch Hlth Sci, Kagoshima 890, Japan. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, 508 Childrens Res Inst,173 Ashley Ave, Charleston, SC 29425 USA. EM khanm@musc.edu FU Veteran Administration; NIH [NS-72511, NS-22576, NS-37766]; National Center for Research Resources [C06 RR018823, C06 RR015455] FX This work was supported by grants from Veteran Administration merit awards and NIH (NS-72511, NS-22576 and NS-37766). This work was also supported by the NIH, Grants C06 RR018823 and No C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources. We thank Ms. Joyce Bryan for her technical help, and Ms. Chara Williams for her secretarial assistance. We also acknowledge Dr. Tom Smith from the MUSC Writing Center for his valuable editing and correction of the manuscript. NR 46 TC 19 Z9 20 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2012 VL 30 IS 5 BP 383 EP 396 DI 10.3233/RNN-2012-110209 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 004UO UT WOS:000308706800003 PM 22717646 ER PT J AU Nomura, Y Hurd, YL Pilowsky, DJ AF Nomura, Yoko Hurd, Yasmin L. Pilowsky, Daniel J. TI Life-Time Risk for Substance Use Among Offspring of Abusive Family Environment From the Community SO SUBSTANCE USE & MISUSE LA English DT Article DE child abuse; craving; parenting skills; risk ID ILLICIT DRUG-USE; CHILDHOOD SEXUAL-ABUSE; MIDDLE ADULTHOOD; NATIONAL SAMPLE; PHYSICAL ABUSE; MALTREATMENT; NEGLECT; ASSOCIATIONS; OUTCOMES; VIOLENCE AB The current study examined the cumulative risk, age of initiation, and functional impairments among adults with substance use problems (N = 1748) by child abuse status. Child abuse was associated with earlier initiation of marijuana, cocaine, and heroin use, and had greater risks for all the drugs studied (hazard ratios, 1.7-3.2). Furthermore, child abuse was associated with increased medical and functional impairments, including ER visits, health problems, drug dealing, drug dependence, and drug cravings. Provision of social services and parenting education during the perinatal period may prevent the long-term impact of child abuse on substance use and related impairments. The study's limitations are noted. C1 [Nomura, Yoko] CUNY, Queens Coll, Dept Psychol, Flushing, NY 11367 USA. [Nomura, Yoko; Hurd, Yasmin L.] Mt Sinai Sch Med, Dept Psychiat, Mt Sinai, NY USA. [Pilowsky, Daniel J.] Columbia Univ, Dept Epidemiolgy, New York, NY USA. [Hurd, Yasmin L.] James J Peters VA Med Ctr, Bronx, NY USA. [Hurd, Yasmin L.] Mt Sinai Sch Med, Dept Pharmacol Syst Therapeut, Mt Sinai, NY USA. [Hurd, Yasmin L.] Mt Sinai Sch Med, Dept Neurosci, Mt Sinai, NY USA. RP Nomura, Y (reprint author), CUNY, Queens Coll, Dept Psychol, 65-30 Kissena Blvd, Flushing, NY 11367 USA. EM yoko.nomura@qc.cuny.edu FU NIDA NIH HHS [R01 DA030359, R01 DA023214]; NIMH NIH HHS [K01 MH080062] NR 51 TC 8 Z9 8 U1 2 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2012 VL 47 IS 12 BP 1281 EP 1292 DI 10.3109/10826084.2012.695420 PG 12 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 005CV UT WOS:000308729000005 PM 22780838 ER PT J AU Mc Causland, FR Prior, LM Heher, E Waikar, SS AF Mc Causland, Finnian R. Prior, Lisa M. Heher, Eliot Waikar, Sushrut S. TI Preservation of Blood Pressure Stability with Hypertonic Mannitol during Hemodialysis Initiation SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Hemodialysis; Intradialytic hypotension; Mannitol; Osmolality ID INTRADIALYTIC HYPOTENSION; DIALYSIS; SODIUM; ULTRAFILTRATION; VOLUME; MAINTENANCE; DYSFUNCTION; MORTALITY AB Background: lntradialytic hypotensive events are common among hemodialysis patients and are associated with a variety of patient- and procedure-related factors, including intradialytic decline in plasma osmolality. Prior studies and practice have suggested that administration of osmotically active drugs may ameliorate blood pressure decline during chronic hennodialysis. Methods: Clinical and treatment data were collected for 102 consecutive patients requiring initiation of renal replacement therapy in 2 major teaching hospitals. Routine administration of mannitol differed according to institutional protocols, allowing its examination as the primary exposure of interest. Generalized linear models were fit to estimate associations of mannitol use during dialysis initiation with intradialytic blood pressure, as assessed by: (1) intradialytic blood pressure decline; (2) nadir intradialytic blood pressure; (3) absolute systolic blood pressure <90 mm Hg or decline >20 mm Hg. Results: Mean age was 62 years (+/- 16), 70% were male and 44% were diabetic. Mean predialysis and nadir systolic blood pressure were 142 mm Hg (+/- 29) and 121 mm Hg (+/- 26), respectively. Mannitol administration was associated with a lesser decline in intradialytic blood pressure, a higher nadir blood pressure and fewer hypotensive events requiring intervention. No effect modification was evident according to diabetes or acuity of kidney disease (chronic vs. acute). Conclusions: Mannitol administration appears to preserve hemodynamic stability during hemodialysis initiation. Randomized controlled trials are needed to confirm these findings and identify optimal management strategies to prevent intradialytic hypotension. Copyright (C) 2012 S. Karger AG, Basel C1 [Mc Causland, Finnian R.; Waikar, Sushrut S.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02446 USA. [Mc Causland, Finnian R.; Heher, Eliot; Waikar, Sushrut S.] Harvard Univ, Sch Med, Boston, MA USA. [Heher, Eliot] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Prior, Lisa M.] Univ Coll Dublin, Sch Med & Med Sci, Dublin 2, Ireland. RP Mc Causland, FR (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, MRB 4, Boston, MA 02446 USA. EM fmccausland@partners.org FU Scholars in Clinical Science Program of Harvard Catalyst; The Harvard Clinical and Translational Science Center [UL1 RR025758]; Harvard University; National Kidney Foundation [2011-13]; [DK075941]; [UO1DK085660] FX This work was conducted with support from the Scholars in Clinical Science Program of Harvard Catalyst, The Harvard Clinical and Translational Science Center (Award No. UL1 RR025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health.; Dr. McCausland is supported by a research fellowship from the National Kidney Foundation (2011-13).; Dr. Waikar is supported by DK075941 and UO1DK085660. NR 26 TC 3 Z9 3 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2012 VL 36 IS 2 BP 168 EP 174 DI 10.1159/000341273 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 998TB UT WOS:000308262200009 PM 22846598 ER PT J AU Karmarkar, AM Dicianno, BE Graham, JE Cooper, R Kelleher, A Cooper, RA AF Karmarkar, Amol M. Dicianno, Brad E. Graham, James E. Cooper, Rosemarie Kelleher, Annmarie Cooper, Rory A. TI Factors Associated with Provision of Wheelchairs in Older Adults SO ASSISTIVE TECHNOLOGY LA English DT Article DE older adults; standard of care; wheelchair prescription; wheelchair seating and mobility clinic ID POWER MOBILITY; ASSISTIVE TECHNOLOGY; STROKE; GUIDELINES; PREDICTORS; VETERANS; SCOOTERS AB The objectives of this study were: to identify the factors that are associated with prescription of wheeled mobility devices for older adults, and to determine the effect that living setting has on the types of devices that older adults receive. Retrospective medical chart review at the Center for Assistive Technology on 337 older individuals. These individuals were aged >60 years, and each of them received a new wheeled mobility device from the center during 2007 or 2008. Data were analyzed in three tiers: tier 1 (manual versus powered mobility devices); tier 2 (motorized scooters versus power wheelchairs); and tier 3 (customized versus standard power wheelchairs). For tier 1, the factor associated with higher odds for receipt of manual wheelchairs versus powered were: cognitive limitations (OR = .03). For tier 2, diagnosis of cardio-vascular and pulmonary conditions were associated with prescription of motorized scooters (OR = 3.9). For tier 3, neurological conditions (OR = 3.1), male gender (OR = .37), institutional living (OR = .23), and lower age (OR = .96) were associated with receipt of customized power wheelchairs. This study objectively describes factors associated with prescription of wheeled mobility for older adults. This information can aid in development of guidelines and improving standards of practice for prescription of wheelchairs for older adults. C1 [Dicianno, Brad E.; Cooper, Rosemarie; Kelleher, Annmarie; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. [Karmarkar, Amol M.; Graham, James E.] Univ Texas Med Branch, Div Rehabil Sci, Galveston, TX USA. [Dicianno, Brad E.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. [Dicianno, Brad E.; Cooper, Rosemarie; Kelleher, Annmarie; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci, Pittsburgh, PA 15260 USA. [Dicianno, Brad E.; Cooper, Rosemarie; Kelleher, Annmarie; Cooper, Rory A.] Univ Pittsburgh, Med Ctr, Ctr Assist Technol, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 7180 Highland Dr,Bldg 4,2nd Floor,151R1-HD, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu RI Karmarkar, Amol/E-6030-2011; OI Karmarkar, Amol/0000-0001-8355-1585; Dicianno, Brad/0000-0003-0738-0192 NR 34 TC 5 Z9 5 U1 1 U2 14 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PY 2012 VL 24 IS 3 BP 155 EP 167 DI 10.1080/10400435.2012.659795 PG 13 WC Rehabilitation SC Rehabilitation GA 996XX UT WOS:000308129200002 PM 23033733 ER PT J AU Zhu, AX AF Zhu, Andrew X. TI Sorafenib Use in Hepatocellular Carcinoma in Japan: Early Experience and Impact on Clinical Practice SO CLINICAL DRUG INVESTIGATION LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-2563 J9 CLIN DRUG INVEST JI Clin. Drug Invest. PY 2012 VL 32 SU 2 BP 1 EP 2 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 994CQ UT WOS:000307908900001 PM 22873622 ER PT J AU Yee, AJ Raje, NS AF Yee, Andrew J. Raje, Noopur S. TI Denosumab, a RANK ligand inhibitor, for the management of bone loss in cancer patients SO CLINICAL INTERVENTIONS IN AGING LA English DT Review DE denosumab; zoledronic acid; bone loss; breast cancer; prostate cancer ID ADJUVANT ENDOCRINE THERAPY; ANDROGEN-DEPRIVATION THERAPY; PLACEBO-CONTROLLED TRIAL; PLUS ZOLEDRONIC ACID; STAGE BREAST-CANCER; PROSTATE-CANCER; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; DOUBLE-BLIND; OSTEOCLAST DIFFERENTIATION AB Bone loss is a common side effect of cancer treatments, especially antihormonal treatments used in the treatment of breast and prostate cancer. Denosumab is a monoclonal antibody given subcutaneously that inhibits osteoclast activity by targeting the RANK ligand. It is effective in settings ranging from preventing skeletal-related complications in cancer patients with metastatic disease to increasing bone mineral density in patients with osteoporosis. In cancer patients with early stage disease, denosumab can attenuate bone loss from antihormonal treatments, and in prostate cancer, may reduce disease progression. Here, we will discuss the important role denosumab may play in the management of bone loss in patients with cancer. C1 [Yee, Andrew J.; Raje, Noopur S.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. RP Yee, AJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ayee1@partners.org NR 55 TC 7 Z9 9 U1 1 U2 3 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-9092 J9 CLIN INTERV AGING JI Clin. Interv. Aging PY 2012 VL 7 BP 331 EP 338 DI 10.2147/CIA.S14566 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 997YK UT WOS:000308204200001 PM 22977302 ER PT J AU Wang, XL Chen, H Geng, Z Zhou, XH AF Wang, Xueli Chen, Hua Geng, Zhi Zhou, Xiaohua TI Using Auxiliary Data for Binomial Parameter Estimation with Nonignorable Nonresponse SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE Identifiability; Information matrix; Nonignorable nonresponse; Odds ratio; Variance estimator ID MISSING OUTCOMES; REGRESSION; SUBJECT; MODELS AB Nonignorable nonresponse is a nonresponse mechanism that depends on the values of the variable having nonresponse. When an observed data of a binomial distribution suffer missing values from a nonignorable nonresponse mechanism, the binomial distribution parameters become unidentifiable without any other auxiliary information or assumption. To address the problems of non identifiability, existing methods mostly based on the log-linear regression model. In this article, we focus on the model when the nonresponse is nonignorable and we consider to use the auxiliary data to improve identifiability; furthermore, we derive the maximum likelihood estimator (MLE) for the binomial proportion and its associated variance. We present results for an analysis of real-life data from the SARS study in China. Finally, the simulation study shows that the proposed method gives promising results. C1 [Wang, Xueli] Beijing Univ Posts & Telecommun, Sch Sci, Beijing 100876, Peoples R China. [Wang, Xueli; Zhou, Xiaohua] Univ Washington, Dept Biostat, Washington, DC USA. [Chen, Hua; Geng, Zhi] Peking Univ, Sch Sci, Beijing 100871, Peoples R China. [Chen, Hua] Inst Appl Phys & Computat Math, Beijing 100088, Peoples R China. [Zhou, Xiaohua] VA Puget Sound Hlth Care Syst, NW HSR&D Ctr Excellence, Seattle, WA USA. [Zhou, Xiaohua] Peking Univ, Beijing Int Ctr Math Res, Beijing 100871, Peoples R China. RP Wang, XL (reprint author), Beijing Univ Posts & Telecommun, Sch Sci, Beijing 100876, Peoples R China. EM wangxlbupt@gmail.com FU National Natural Science Foundation of China [NSFC 10801019]; Fundamental Research Funds for the Central Universities [BUPT 2012RC0708] FX The authors would like to thank the Co-Editor, an Associate Editor, and anonymous referees for their valuable suggestions which greatly improved the presentation of this article. This research was supported by the National Natural Science Foundation of China (NSFC 10801019) and the Fundamental Research Funds for the Central Universities (BUPT 2012RC0708). Xiao-Hua (Andrew) Zhou, Ph.D., is presently a Core Investigator and Biostatistics Unit Director at the Northwest HSR&D Center of Excellence, Department of Veterans Affairs Medical Center, Seattle, WA. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 17 TC 0 Z9 0 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0926 EI 1532-415X J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2012 VL 41 IS 19 BP 3468 EP 3478 DI 10.1080/03610926.2011.620209 PG 11 WC Statistics & Probability SC Mathematics GA 001MW UT WOS:000308465800002 ER PT J AU Kane-Gill, SL Forsberg, EA Verrico, MM Handler, SM AF Kane-Gill, Sandra L. Forsberg, Elizabeth A. Verrico, Margaret M. Handler, Steven M. TI Comparison of Three Pharmacovigilance Algorithms in the ICU Setting A Retrospective and Prospective Evaluation of ADRs SO DRUG SAFETY LA English DT Article ID ADVERSE DRUG-REACTIONS; INTENSIVE-CARE-UNIT; HOSPITALIZED-PATIENTS; CAUSALITY ASSESSMENT; EVENTS; ERRORS; IMPUTABILITY; PRINCIPLES; PROPOSAL; SAFETY AB Background: Pharmacovigilance algorithms are used to assess the likelihood of adverse drug reaction (ADR) occurrence. The preferred instrument for use in the intensive care unit (ICU) is not established. Objective: The primary objective of this study was to compare the agreement between the Kramer algorithm, Naranjo criteria and Jones algorithm for the evaluation of ADRs in the ICU. A secondary objective was to compare the agreement between the same pharmacovigilance algorithms for ADR determination when applied in a retrospective versus concurrent fashion in the ICU. Study Design: There were two phases in this study. Phase I was the retrospective evaluation (i.e. after the patient was discharged from the hospital) conducted in patients admitted during July 2005 to June 2006. Phase II was the concurrent phase (i.e. while the patient was in the hospital) conducted over 6 weeks in 2008. Both phases were conducted at the University of Pittsburgh Medical Center and included adult patients admitted to the medical ICU. Intervention: In phase I, a random sample of 261 medication signals were evaluated individually for potential ADRs using the Kramer algorithm, Naranjo criteria and Jones algorithm. In phase II, an active medication monitoring system was used to detect five abnormal laboratory values, resulting in a random sample of 253 signals that were evaluated using the same three algorithms. Main Outcome Measure: Percentage agreement among the algorithms for all levels of causality was estimated using a kappa statistic for both phases of the study. Results: For phase I, the kappa values were all >0.7 ranging from 0.721 to 0.855 between instruments, with Naranjo versus Kramer having the highest kappa, which is considered excellent agreement. The kappa statistic between individual instruments for phase 11 are <0.7 ranging from 0.423 to 0.635, which is considered moderate agreement, with Naranjo versus Jones displaying the lowest kappa while still exhibiting moderate agreement. For phase II, the Kramer algorithm had better agreement with both the Naranjo criteria and the Jones algorithm. Conclusions: These instruments demonstrated similar results for evaluating ADRs in the ICU retrospectively, suggesting that instrument selection with any of the three instruments is reasonable. For concurrent ADR evaluations, there is greater variability in the level of causality obtained among pharmacovigilance algorithms and Kramer displayed better agreement with its comparators. A suggestion for a more definitive concurrent ADR assessment is to use more than one algorithm. This may be challenging in daily clinical practice; however, it is a reasonable expectation for research. C1 [Kane-Gill, Sandra L.] Univ Pittsburgh, Sch Pharm, Ctr Pharmacoinformat & Outcomes Res, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Forsberg, Elizabeth A.; Verrico, Margaret M.] Univ Pittsburgh Med Ctr Presbyterian Shadyside, Dept Pharm, Pittsburgh, PA USA. [Kane-Gill, Sandra L.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA 15261 USA. [Forsberg, Elizabeth A.] Univ Pittsburgh, St Margaret Hosp, Med Ctr, Dept Pharm, Pittsburgh, PA 15261 USA. [Handler, Steven M.] Univ Pittsburgh, Sch Med, Dept Biomed Informat, Pittsburgh, PA 15261 USA. [Handler, Steven M.] Geriatr Pharmaceut Outcomes & Geroinformat Res &, Pittsburgh, PA USA. [Handler, Steven M.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA 15261 USA. [Handler, Steven M.] Vet Affairs Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. [Handler, Steven M.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Kane-Gill, SL (reprint author), Univ Pittsburgh, Sch Pharm, Ctr Pharmacoinformat & Outcomes Res, Dept Pharm & Therapeut, 918 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM SLK54@pitt.edu OI Kane-GIll, Sandra/0000-0001-7523-4846 FU Agency for Healthcare Research and Quality grant [R01-HS017695]; National Institute on Aging grant [K07AG033174] FX This work was funded in part by an Agency for Healthcare Research and Quality grant (R01-HS017695) and National Institute on Aging grant (K07AG033174) awarded to Dr Steven Handler. The authors have no conflict of interests to disclose. NR 48 TC 10 Z9 10 U1 0 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2012 VL 35 IS 8 BP 645 EP 653 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 986DH UT WOS:000307320600005 PM 22720659 ER PT J AU Sarris, J Moylan, S Camfield, DA Pase, MP Mischoulon, D Berk, M Jacka, FN Schweitzer, I AF Sarris, J. Moylan, S. Camfield, D. A. Pase, M. P. Mischoulon, D. Berk, M. Jacka, F. N. Schweitzer, I. TI Complementary Medicine, Exercise, Meditation, Diet, and Lifestyle Modification for Anxiety Disorders: A Review of Current Evidence SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Review ID ST-JOHNS-WORT; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; OBSESSIVE-COMPULSIVE DISORDER; COMMUNITY-DWELLING ADULTS; STRESS REDUCTION PROGRAM; COMMON MENTAL-DISORDERS; OFFICINALIS LEMON BALM; ALL-CAUSE MORTALITY; PHYSICAL-ACTIVITY AB Use of complementary medicines and therapies (CAM) and modification of lifestyle factors such as physical activity and exercise, and diet are being increasingly considered as potential therapeutic options for anxiety disorders. The objective of this metareview was to examine evidence across a broad range of CAM and lifestyle interventions in the treatment of anxiety disorders. In early 2012 we conducted a literature search of PubMed, Scopus, CINAHL, Web of Science, PsycInfo, and the Cochrane Library, for key studies, systematic reviews, and metaanalyses in the area. Our review found that in respect to treatment of generalized anxiety or specific anxiety disorders, CAM evidence revealed support for the herbal medicine Kava. One isolated study shows benefit for naturopathic medicine, whereas acupuncture, yoga, and Tai chi have tentative supportive evidence, which is hampered by overall poor methodology. The breadth of evidence does not support homeopathy for treating anxiety. Strong support exists for lifestyle modifications including adoption of moderate exercise and mindfulness meditation, whereas dietary improvement, avoidance of caffeine, alcohol, and nicotine offer encouraging preliminary data. In conclusion, certain lifestyle modifications and some CAMs may provide a beneficial role in the management of anxiety disorders. C1 [Sarris, J.; Berk, M.; Jacka, F. N.; Schweitzer, I.] Univ Melbourne, Dept Psychiat, Melbourne, Vic 3000, Australia. [Sarris, J.; Camfield, D. A.; Pase, M. P.] Swinburne Univ Technol, Ctr Human Psychopharmacol, Melbourne, Vic 3122, Australia. [Sarris, J.; Camfield, D. A.; Pase, M. P.] NICM Collaborat Ctr Neurocognit, Melbourne, Vic 3122, Australia. [Moylan, S.; Berk, M.; Jacka, F. N.] Deakin Univ, Geelong, Vic 3220, Australia. [Mischoulon, D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02114 USA. [Berk, M.] Mental Hlth Res Inst, Parkville, Vic 3052, Australia. [Berk, M.] Orygen Youth Hlth Res Ctr, Parkville, Vic 3052, Australia. RP Sarris, J (reprint author), Univ Melbourne, Dept Psychiat, Melbourne, Vic 3000, Australia. EM jsarris@unimelb.edu.au OI Camfield, David/0000-0001-7925-2566; Pase, Matthew/0000-0002-4143-8485; Berk, Michael/0000-0002-5554-6946 FU Australian National Health and Medical Research Council fellowship (NHMRC) [628875, 628912]; University of Melbourne; Centre for Human Psychopharmacology at Swinburne University of Technology FX Dr. J. Sarris is funded by an Australian National Health and Medical Research Council fellowship (NHMRC funding ID 628875), in a strategic partnership with The University of Melbourne and The Centre for Human Psychopharmacology at Swinburne University of Technology. Dr. F. Jacka is supported by an Australian National Health and Medical Research Council Fellowship (NHMRC funding ID 628912). NR 193 TC 11 Z9 11 U1 11 U2 66 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2012 AR 809653 DI 10.1155/2012/809653 PG 20 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 001OY UT WOS:000308471200001 ER PT J AU Segata, N Haake, SK Mannon, P Lemon, KP Waldron, L Gevers, D Huttenhower, C Izard, J AF Segata, Nicola Haake, Susan Kinder Mannon, Peter Lemon, Katherine P. Waldron, Levi Gevers, Dirk Huttenhower, Curtis Izard, Jacques TI Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples SO GENOME BIOLOGY LA English DT Article ID HUMAN GUT MICROBIOTA; ORAL-CAVITY; GEN. NOV.; INTESTINAL MICROBIOTA; ULCERATIVE-COLITIS; SUBGINGIVAL PLAQUE; MOLECULAR ANALYSIS; ESCHERICHIA-COLI; HYDROGEN-SULFIDE; HUMAN FECES AB Background: To understand the relationship between our bacterial microbiome and health, it is essential to define the microbiome in the absence of disease. The digestive tract includes diverse habitats and hosts the human body's greatest bacterial density. We describe the bacterial community composition of ten digestive tract sites from more than 200 normal adults enrolled in the Human Microbiome Project, and metagenomically determined metabolic potentials of four representative sites. Results: The microbiota of these diverse habitats formed four groups based on similar community compositions: buccal mucosa, keratinized gingiva, hard palate; saliva, tongue, tonsils, throat; sub-and supra-gingival plaques; and stool. Phyla initially identified from environmental samples were detected throughout this population, primarily TM7, SR1, and Synergistetes. Genera with pathogenic members were well-represented among this disease-free cohort. Tooth-associated communities were distinct, but not entirely dissimilar, from other oral surfaces. The Porphyromonadaceae, Veillonellaceae and Lachnospiraceae families were common to all sites, but the distributions of their genera varied significantly. Most metabolic processes were distributed widely throughout the digestive tract microbiota, with variations in metagenomic abundance between body habitats. These included shifts in sugar transporter types between the supragingival plaque, other oral surfaces, and stool; hydrogen and hydrogen sulfide production were also differentially distributed. Conclusions: The microbiomes of ten digestive tract sites separated into four types based on composition. A core set of metabolic pathways was present across these diverse digestive tract habitats. These data provide a critical baseline for future studies investigating local and systemic diseases affecting human health. C1 [Lemon, Katherine P.; Izard, Jacques] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Segata, Nicola; Waldron, Levi; Huttenhower, Curtis] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Haake, Susan Kinder] Univ Calif Los Angeles, Sect Periodont, Sch Dent, Los Angeles, CA 90095 USA. [Haake, Susan Kinder] Univ Calif Los Angeles, Sch Dent, Dent Res Inst, Los Angeles, CA 90095 USA. [Mannon, Peter] Univ Alabama Birmingham, Div Gastroenterol & Hepatol, Birmingham, AL 35205 USA. [Lemon, Katherine P.] Harvard Univ, Sch Med, Div Infect Dis, Childrens Hosp Boston, Boston, MA 02115 USA. [Gevers, Dirk] Broad Inst MIT & Harvard, Cambridge Ctr 7, Microbial Syst & Communities Genome Sequencing &, Cambridge, MA 02142 USA. [Izard, Jacques] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Izard, J (reprint author), Forsyth Inst, Dept Mol Genet, 245 1st St, Cambridge, MA 02142 USA. EM jizard@forsyth.org OI Izard, Jacques/0000-0002-5904-5436; Waldron, Levi/0000-0003-2725-0694; Huttenhower, Curtis/0000-0002-1110-0096; Segata, Nicola/0000-0002-1583-5794 FU Army Research Office (ARO) [W911NF-11-1-0473]; National Science Foundation (NSF) [DBI-1053486]; National Institutes of Health (NIH) [HG005969, HG004969, CA139193, DE020751, DE020298, DE021574] FX We thank the other members of the Human Microbiome Project consortium for study design and data production with special thanks to Patrick Schloss and the HMP Metabolic Reconstruction Group for providing the tables from which this analysis is derived. The human subjects who participated in this study are gratefully acknowledged. We thank Joshua A Reyes for participating in the production of Additional file 11. This work was supported by the Army Research Office (ARO) under award W911NF-11-1-0473 to CH, by the National Science Foundation (NSF) under award DBI-1053486 to CH, and by the National Institutes of Health (NIH) under awards HG005969 to CH, HG004969 to DG, CA139193 to JI, DE020751 to KPL, DE020298 and DE021574 to SKH. NR 102 TC 169 Z9 171 U1 7 U2 56 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-7596 J9 GENOME BIOL JI Genome Biol. PY 2012 VL 13 IS 6 AR R42 DI 10.1186/gb-2012-13-6-r42 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 002QD UT WOS:000308546300002 PM 22698087 ER PT J AU Lee, CJ Ramirez, AS Lewis, N Gray, SW Hornik, RC AF Lee, Chul-joo Ramirez, A. Susana Lewis, Nehama Gray, Stacy W. Hornik, Robert C. TI Looking Beyond the Internet: Examining Socioeconomic Inequalities in Cancer Information Seeking Among Cancer Patients SO HEALTH COMMUNICATION LA English DT Article ID HEALTH INFORMATION; KNOWLEDGE GAP; NEWS; DISPARITIES; BEHAVIORS; COVERAGE; CARE AB The gap in cancer information seeking between high-socioeconomic-status (high-SES) cancer patients and low-SES cancer patients deserves serious attention, considering the importance of information and knowledge in cancer control. We thus explored the association of SES, as measured by education, with cancer patients' overall cancer information seeking, and with seeking from each source (i.e., the Internet, mass media, medical sources, and nonmedical interpersonal sources) and across two topic categories (i.e., treatment, quality of life). We then asked whether the effect of education on treatment information seeking is reduced among those who are particularly motivated to control treatment choices. We conducted a survey with breast, prostate, and colon cancer patients diagnosed in 2005 (n = 2,013), who were randomly drawn from the Pennsylvania Cancer Registry in the fall of 2006. We found that education was more strongly associated with Internet use than with the use of other sources regardless of topics. Also, when information was sought from mass media, education had a greater association with treatment information seeking than with quality-of-life information seeking. Preference for active participation in treatment decision making, however, did not moderate the effect of education on treatment information seeking. The implications of these findings for public health research and cancer patient education were discussed. C1 [Lee, Chul-joo] Ohio State Univ, Sch Commun, Columbus, OH 43210 USA. [Ramirez, A. Susana] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Lewis, Nehama] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA. [Gray, Stacy W.] Harvard Univ, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Hornik, Robert C.] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. RP Lee, CJ (reprint author), Ohio State Univ, Sch Commun, 3062 Derby Hall,154 N Oval Mall, Columbus, OH 43210 USA. EM lee.4030@osu.edu OI Hornik, Robert/0000-0002-2148-8805 FU NCI NIH HHS [5P50CA095856-05, P50 CA095856] NR 44 TC 9 Z9 9 U1 4 U2 16 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1041-0236 J9 HEALTH COMMUN JI Health Commun. PY 2012 VL 27 IS 8 BP 806 EP 817 DI 10.1080/10410236.2011.647621 PG 12 WC Communication; Health Policy & Services SC Communication; Health Care Sciences & Services GA 994SW UT WOS:000307953200008 PM 22356137 ER PT J AU Yeterian, JD Dow, SJ Kelly, JF AF Yeterian, Julie D. Dow, Sarah J. Kelly, John F. TI Ensuring retention in longitudinal studies: a practical evaluation of an intensive follow-up protocol and suggested adaptations SO INTERNATIONAL JOURNAL OF SOCIAL RESEARCH METHODOLOGY LA English DT Article DE adolescent; substance use; follow-up protocol; longitudinal ID SUBSTANCE USE; ADOLESCENTS; ATTRITION; DRINKING; OUTCOMES AB Ensuring retention in longitudinal studies of individuals with substance use disorders (SUD) is a continual challenge for researchers. This study made several modifications to a highly intensive follow-up protocol, originally designed for adults with SUD, in order to adapt it to a group of adolescents in low intensity outpatient SUD treatment (N = 127, M age 16.7 years) and to accommodate limitations in the financial resources available for study staffing and transportation. In the present sample, adolescent participants generally found it unreasonable for study staff to request to contact people outside their immediate family in order to locate them and to attempt to schedule interviews 3-6 months in advance, as specified in the original protocol. Changes were made to accommodate these concerns and follow-up rates remained high (85-91%). Even though this study is limited by its non-experimental nature, it provides a replicable example of a scaled-down, less costly version of a highly intensive follow-up protocol that can be used to achieve high follow-up rates in studies of adolescents with SUD. We hope this will be encouraging for researchers and program evaluators who have limited resources or who work with participants who express concerns about privacy or study burden. C1 [Yeterian, Julie D.; Kelly, John F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Yeterian, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM jyeterian@partners.org NR 18 TC 2 Z9 2 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1364-5579 J9 INT J SOC RES METHOD JI Int. J. Soc. Res. Methodol. PY 2012 VL 15 IS 5 BP 369 EP 383 DI 10.1080/13645579.2011.623958 PG 15 WC Social Sciences, Interdisciplinary SC Social Sciences - Other Topics GA 996RO UT WOS:000308111800002 ER PT J AU Stein, MB Slavin-Mulford, J Sinclair, SJ Siefert, CJ Blais, MA AF Stein, Michelle B. Slavin-Mulford, Jenelle Sinclair, S. Justin Siefert, Caleb J. Blais, Mark A. TI Exploring the Construct Validity of the Social Cognition and Object Relations Scale in a Clinical Sample SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID ASSESSMENT INVENTORY PAI; EARLY MEMORIES; TAT; SCORS; PSYCHOPATHOLOGY; REPRESENTATIONS; RELIABILITY; DEPRESSION; ANXIETY; UTILITY AB The Social Cognition and Object Relations Scale-Global rating method (SCORS-G; Stein, Hilsenroth, Slavin-Mulford, & Pinsker, 2011; Westen, 1995) measures the quality of object relations in narrative material. This study employed a multimethod approach to explore the structure and construct validity of the SCORS-G. The Thematic Apperception Test (TAT; Murray, 1943) was administered to 59 patients referred for psychological assessment at a large Northeastern U. S. hospital. The resulting 301 TAT narratives were rated using the SCORS-G method. The 8 SCORS variables were found to have high interrater reliability and good internal consistency. Principal components analysis revealed a 3-component solution with components tapping emotions/affect regulation in relationships, self-image, and aspects of cognition. Next, the construct validity of the SCORS-G components was explored using measures of intellectual and executive functioning, psychopathology, and normal personality. The 3 SCORS-G components showed unique and theoretically meaningful relationships across these broad and diverse psychological measures. This study demonstrates the value of using a standardized scoring method, like the SCORS-G, to reveal the rich and complex nature of narrative material. C1 [Stein, Michelle B.; Slavin-Mulford, Jenelle; Sinclair, S. Justin; Blais, Mark A.] Massachusetts Gen Hosp, Psychol Evaluat & Res Lab PEaRL, Boston, MA 02114 USA. [Stein, Michelle B.; Slavin-Mulford, Jenelle; Sinclair, S. Justin; Blais, Mark A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Siefert, Caleb J.] Univ Michigan, Dept Psychol, Dearborn, MI 48128 USA. RP Stein, MB (reprint author), Massachusetts Gen Hosp, Psychol Evaluat & Res Lab PEaRL, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mstein3@partners.org NR 52 TC 7 Z9 7 U1 3 U2 17 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PY 2012 VL 94 IS 5 BP 533 EP 540 DI 10.1080/00223891.2012.668594 PG 8 WC Psychology, Clinical; Psychology, Social SC Psychology GA 994TE UT WOS:000307954100010 PM 22448959 ER PT J AU Li, H Weiser-Evans, MCM Nemenoff, R AF Li, Howard Weiser-Evans, Mary C. M. Nemenoff, Raphael TI Anti- and Protumorigenic Effects of PPAR gamma in Lung Cancer Progression: A Double-Edged Sword SO PPAR RESEARCH LA English DT Review ID ACTIVATED-RECEPTOR-GAMMA; HEPATIC STELLATE CELLS; MACROPHAGE-GENE-EXPRESSION; HUMAN PROSTATE-CANCER; RETINOID-X-RECEPTOR; HUMAN BREAST-CANCER; REGULATORY T-CELLS; TUMOR PROGRESSION; IN-VITRO; HEPATOCELLULAR-CARCINOMA AB Peroxisome proliferator-activated receptor-gamma ( PPAR gamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors that plays an important role in the control of gene expression linked to a variety of physiological processes, including cancer. Ligands for PPAR. include naturally occurring fatty acids and the thiazolidinedione class of antidiabetic drugs. Activation of PPAR gamma in a variety of cancer cells leads to inhibition of growth, decreased invasiveness, reduced production of proinflammatory cytokines, and promotion of a more differentiated phenotype. However, systemic activation of PPAR gamma has been reported to be protumorigenic in some in vitro systems and in vivo models. Here, we review the available data that implicate PPAR gamma in lung carcinogenesis and highlight the challenges of targeting PPAR gamma in lung cancer treatments. C1 [Weiser-Evans, Mary C. M.; Nemenoff, Raphael] Univ Colorado Denver, Dept Med, Div Renal Dis & Hypertens, Aurora, CO 80045 USA. [Li, Howard] Univ Colorado Denver, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Li, Howard] Denver Vet Affairs Med Ctr, Dept Med, Pulm & Crit Care Sect, Denver, CO 80220 USA. [Nemenoff, Raphael] Univ Colorado, Dept Med, Div Renal Dis & Hypertens, Aurora, CO 80045 USA. RP Nemenoff, R (reprint author), Univ Colorado Denver, Dept Med, Div Renal Dis & Hypertens, Aurora, CO 80045 USA. EM raphael.nemenoff@ucdenver.edu OI Li, Howard/0000-0002-1230-2941 NR 121 TC 2 Z9 2 U1 0 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2012 AR 362085 DI 10.1155/2012/362085 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 997SF UT WOS:000308185700001 ER PT J AU Budin, G Chung, HJ Lee, H Weissleder, R AF Budin, Ghyslain Chung, Hyun Jung Lee, Hakho Weissleder, Ralph TI A Magnetic Gram Stain for Bacterial Detection SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE bacteria; biosensors; cycloaddition; imaging agents; nanoparticles ID PATHOGEN DETECTION; NANOPARTICLES C1 [Budin, Ghyslain; Chung, Hyun Jung; Lee, Hakho; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu RI Chung, Hyun Jung/J-3205-2014 FU National Institutes of Health (NIH) [2P50CA086355] FX This work was supported by the National Institutes of Health (NIH) grant number 2P50CA086355. We thank Yoshi Iwamoto and Alex Zaltsman for image processing. NR 16 TC 26 Z9 26 U1 5 U2 47 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2012 VL 51 IS 31 BP 7752 EP 7755 DI 10.1002/anie.201202982 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 978PS UT WOS:000306757900024 PM 22744868 ER PT J AU McNairy, ML Wurcel, AG Huang, F Daily, JP AF McNairy, Margaret L. Wurcel, Alysse G. Huang, Franklin Daily, Johanna P. TI Health care workers in Africa access a broad range of topics using evidence-based online medical information SO GLOBAL PUBLIC HEALTH LA English DT Article DE evidence-based medicine; Internet; resource-limited settings; medical knowledge resources; Africa; Internet-based health information ID CLINICAL-PRACTICE; RESOURCES; COUNTRIES; DIVIDE AB Health care workers (HCW) rely on Internet-based medical resources to obtain current evidence-based clinical guidelines. While such resources are being used with increasing frequency in developed countries, they have not been broadly employed in resource-limited settings (RLS). To investigate the feasibility and the types of medical content used by HCW in RLS, we studied one Internet-based medical resource used in the United States, (UpToDate (c)) in four hospitals in Africa. Health care workers were trained on how to use this resource and surveyed over a six month study period. Automated topic tracking found that HCW searched a variety of medical topics. About 78% of HCW reported daily or weekly use of the Internet-based medical resource and 70% felt the tool was very useful for teaching. All users report the tool increased their clinical knowledge. This descriptive study suggests that Internet-based medical information resources are feasible in RLS and are accessed for a broad variety of medical topics. Supplemental content providing guidance when minimal diagnostic and therapeutic options exist could increase its relevance in RLS. With increased availability, Internet-based medical information could enhance current global health care initiatives to improve providers' knowledge, clinical practice and potentially patient outcomes. C1 [Wurcel, Alysse G.] Columbia Univ, Dept Infect Dis, New York, NY 10027 USA. [McNairy, Margaret L.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [McNairy, Margaret L.] Columbia Univ, ICAP, New York, NY USA. [Huang, Franklin] Dana Farber Inst, Boston, MA USA. [Daily, Johanna P.] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Wurcel, AG (reprint author), Columbia Univ, Dept Infect Dis, New York, NY 10027 USA. EM alysse@gmail.com NR 24 TC 4 Z9 4 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1744-1692 J9 GLOB PUBLIC HEALTH JI Glob. Public Health PY 2012 VL 7 IS 8 BP 823 EP 839 DI 10.1080/17441692.2012.685488 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 995SA UT WOS:000308031400003 PM 22621407 ER PT J AU Wallis, TSA Bex, PJ AF Wallis, Thomas S. A. Bex, Peter J. TI Image correlates of crowding in natural scenes SO JOURNAL OF VISION LA English DT Article DE crowding; texture; contours; natural scenes; anisotropy; pooling; feature integration; peripheral vision; reverse correlation; Bayesian Information Criterion; model selection ID OBJECT RECOGNITION; PERIPHERAL-VISION; PSYCHOMETRIC FUNCTION; SURROUND SUPPRESSION; CONTRAST SENSITIVITY; SPATIAL INTERACTION; MODEL SELECTION; BAYES FACTORS; MASKING; DISCRIMINATION AB Visual crowding is the inability to identify visible features when they are surrounded by other structure in the peripheral field. Since natural environments are replete with structure and most of our visual field is peripheral, crowding represents the primary limit on vision in the real world. However, little is known about the characteristics of crowding under natural conditions. Here we examine where crowding occurs in natural images. Observers were required to identify which of four locations contained a patch of "dead leaves'' (synthetic, naturalistic contour structure) embedded into natural images. Threshold size for the dead leaves patch scaled with eccentricity in a manner consistent with crowding. Reverse correlation at multiple scales was used to determine local image statistics that correlated with task performance. Stepwise model selection revealed that local RMS contrast and edge density at the site of the dead leaves patch were of primary importance in predicting the occurrence of crowding once patch size and eccentricity had been considered. The absolute magnitudes of the regression weights for RMS contrast at different spatial scales varied in a manner consistent with receptive field sizes measured in striate cortex of primate brains. Our results are consistent with crowding models that are based on spatial averaging of features in the early stages of the visual system, and allow the prediction of where crowding is likely to occur in natural images. C1 [Wallis, Thomas S. A.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Wallis, Thomas S. A.] Univ Western Australia, Perth, WA 6009, Australia. RP Wallis, TSA (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM thomas.wallis@schepens.harvard.edu OI Wallis, Thomas/0000-0001-7431-4852 FU NIH [R01EY019281]; NHMRC [634560] FX Supported by NIH grant R01EY019281 to PB and NHMRC Research Fellowship 634560 to TW. NR 101 TC 3 Z9 3 U1 2 U2 17 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 1534-7362 J9 J VISION JI J. Vision PY 2012 VL 12 IS 7 AR 6 DI 10.1167/12.7.6 PG 19 WC Ophthalmology SC Ophthalmology GA 983MZ UT WOS:000307124700006 ER PT J AU Fargo, J Metraux, S Byrne, T Munley, E Montgomery, AE Jones, H Sheldon, G Kane, V Culhane, D AF Fargo, Jamison Metraux, Stephen Byrne, Thomas Munley, Ellen Montgomery, Ann Elizabeth Jones, Harlan Sheldon, George Kane, Vincent Culhane, Dennis TI Prevalence and Risk of Homelessness Among US Veterans SO PREVENTING CHRONIC DISEASE LA English DT Article ID MEN; PROPORTION AB Introduction Understanding the prevalence of and risk for homelessness among veterans is prerequisite to preventing and ending homelessness among this population. Homeless veterans are at higher risk for chronic disease; understanding the dynamics of homelessness among veterans can contribute to our understanding of their health needs. Methods We obtained data on demographic characteristics and veteran status for 130,554 homeless people from 7 jurisdictions that provide homelessness services, and for the population living in poverty and the general population from the American Community Survey for those same jurisdictions. We calculated prevalence of veterans in the homeless, poverty, and general populations, and risk ratios (RR) for veteran status in these populations. Risk for homelessness, as a function of demographic characteristics and veteran status, was estimated by using multivariate regression models. Results Veterans were overrepresented in the homeless population, compared with both the general and poverty populations, among both men (RR, 1.3 and 2.1, respectively) and women (RR, 2.1 and 3.0, respectively). Veteran status and black race significantly increased the risk for homelessness for both men and women. Men in the 45- to 54-year-old age group and women in the 18- to 29-year-old age group were at higher risk compared with other ages. Conclusion Our findings confirm previous research associating veteran status with higher risk for homelessness and imply that there will be specific health needs among the aging homeless population. This study is a basis for understanding variation in rates of, and risks for, homelessness in general population groups, and inclusion of health data from US Department of Veterans Affairs records can extend these results to identifying links between homelessness and health risks. C1 [Metraux, Stephen; Byrne, Thomas; Munley, Ellen; Montgomery, Ann Elizabeth; Jones, Harlan; Kane, Vincent; Culhane, Dennis] Natl Ctr Homelessness Vet, Philadelphia, PA USA. [Metraux, Stephen] Univ Sci, Philadelphia, PA USA. [Byrne, Thomas; Montgomery, Ann Elizabeth; Jones, Harlan; Culhane, Dennis] Univ Penn, Philadelphia, PA 19104 USA. [Munley, Ellen] CUNY, Philadelphia, PA USA. [Sheldon, George] US Dept Vet Affairs, Washington, DC USA. RP Fargo, J (reprint author), Natl Ctr Homelessness Vet, 2810 Old Main Hill St, Logan, UT 84322 USA. EM jamison.fargo@usu.edu NR 27 TC 11 Z9 11 U1 4 U2 28 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2012 VL 9 AR 110112 DI 10.5888/pcd9.110112 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 977GI UT WOS:000306644300045 ER PT J AU Main, DS Ware, G Iwasaki, PG Burry, M Steiner, E Fedde, K Haverhals, LM AF Main, Deborah S. Ware, George Iwasaki, Patricia G. Burry, Mark Steiner, Emily Fedde, Katherine Haverhals, Leah M. TI Taking Neighborhood Health to Heart (TNH2H): Building a Community-Based Participatory Data System SO PREVENTING CHRONIC DISEASE LA English DT Article ID PHYSICAL-ACTIVITY; BIAS AB Background Healthy People 2020 calls for increased monitoring of local health and health disparities, but successful models of designing and implementing data collection systems for this purpose are lacking. Community Context We describe the process, methods, and outcomes of a community-based participatory research initiative, Taking Neighborhood Health to Heart, designed to collect and disseminate comprehensive health data from 5 diverse urban neighborhoods in Denver, Colorado. Methods Since its beginning in 2006, this initiative has involved community members in collection of individual health surveys from 1,146 households; audits of sidewalks, buildings, and other built environment features in 412 neighborhood blocks; audits of availability, price, and quality of fresh produce in 69 local stores; and audits of conditions and amenities in 20 local parks. Community members and researchers share, interpret, and disseminate these data through a joint data review and dissemination committee. Outcome Through our community-based data collection system, Taking Neighborhood Health to Heart has been able to collect, analyze, and disseminate locally relevant data on people and neighborhoods to monitor heath and health disparities. Interpretation Since 2006, the initiative has sustained its focus on community-based participatory research that targets collection and dissemination of local health data. We have used this information to identify salient health issues and advocate for neighborhood programs, policies, and environmental changes to built and social features of neighborhoods that have historically led to unequal opportunities and social disadvantage. C1 [Main, Deborah S.] Univ Colorado, Dept Hlth & Behav Sci, Denver, CO 80217 USA. [Ware, George] Colorado Dept Publ Hlth & Environm, Denver, CO USA. [Iwasaki, Patricia G.] Univ Denver, Denver, CO USA. [Haverhals, Leah M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Main, DS (reprint author), Univ Colorado, Dept Hlth & Behav Sci, 1201 5th St,Suite 280J,POB 173364, Denver, CO 80217 USA. EM Debbi.Main@ucdenver.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health grant [R21HL083866] FX TNH2H was funded by a National Heart, Lung, and Blood Institute, National Institutes of Health grant (R21HL083866) to Dr Main. We acknowledge the hard work and dedication of community members and researchers participating in the TNH2H Council, steering committee, data review and dissemination committee, and the food committee. NR 16 TC 0 Z9 0 U1 0 U2 10 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2012 VL 9 AR 110058 DI 10.5888/pcd9.110058 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 977GI UT WOS:000306644300041 ER PT J AU McNeill, LH Emmons, K AF McNeill, Lorna H. Emmons, Karen TI GIS Walking Maps to Promote Physical Activity in Low-Income Public Housing Communities: a Qualitative Examination SO PREVENTING CHRONIC DISEASE LA English DT Article ID AFRICAN-AMERICAN; ADULTS; NEIGHBORHOODS; DISPARITIES; WOMEN; URBAN; OLDER AB Introduction Walking is the most commonly reported leisure-time activity. Members of racial/ethnic minority groups and people of low socioeconomic status disproportionately live in urban environments that are perceived to be unsafe, thereby reducing opportunities for engaging in walking. We examined the use of walking maps for increasing physical activity (PA) among low-income residents of public housing sites in Boston, Massachusetts. Methods PA facilities, local businesses, and destinations in a walkable half-mile radius of the housing community were identified and plotted on maps by using geographic information systems technology. Four focus groups (n = 24) were conducted to learn how the walking maps were used by the residents and to understand map features that promoted use. Results Maps were used by participants to increase their PA, and use of the maps increased participants' awareness of community resources. Maps changed participants' perception of distances and were discussed as a means of fostering a sense of community. Use of the maps also increased participants' awareness of neighborhood incivilities. Barriers to map use were difficulty in interpreting the maps and lack of access to the maps. Conclusion Walking maps that display PA opportunities and resources may be useful in increasing walking among residents of public housing sites. C1 [Emmons, Karen] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Emmons, Karen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP McNeill, LH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Unit 1440, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM lmcneill@mdanderson.org FU National Cancer Institute [5R01CA098864-02, 5K05CA124415-04]; Liberty Mutual; National Grid; Patterson Fellowship Fund; Yerby Postdoctoral Fellowship Program at Harvard School of Public Health FX This research was supported by grants 5R01CA098864-02 and 5K05CA124415-04 from the National Cancer Institute and support to the Dana-Farber Cancer Institute by Liberty Mutual, National Grid, and the Patterson Fellowship Fund, and the Yerby Postdoctoral Fellowship Program at Harvard School of Public Health. NR 22 TC 3 Z9 3 U1 3 U2 17 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1545-1151 J9 PREV CHRONIC DIS JI Prev. Chronic Dis. PD JAN PY 2012 VL 9 AR 110086 DI 10.5888/pcd9.110086 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 977GI UT WOS:000306644300017 ER PT J AU Spiro, A Settersten, RA AF Spiro, Avron, III Settersten, Richard A., Jr. TI Long-Term Implications of Military Service for Later-Life Health and Well-Being INTRODUCTION SO RESEARCH IN HUMAN DEVELOPMENT LA English DT Editorial Material ID WORLD-WAR-II; VETERANS; WARTIME; TRAJECTORIES; TRAUMA C1 [Spiro, Avron, III] VA Boston Healthcare Syst, MAVERIC NAS 151MAV, Boston, MA 02130 USA. [Spiro, Avron, III] Boston Univ, Boston, MA 02215 USA. [Settersten, Richard A., Jr.] Oregon State Univ, Corvallis, OR 97331 USA. RP Spiro, A (reprint author), VA Boston Healthcare Syst, MAVERIC NAS 151MAV, 150 S Huntington Ave, Boston, MA 02130 USA. EM aspiro3@bu.edu NR 19 TC 2 Z9 2 U1 0 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1542-7609 J9 RES HUM DEV JI Res. Hum. Dev. PY 2012 VL 9 IS 3 SI SI BP 183 EP 190 DI 10.1080/15427609.2012.705551 PG 8 WC Psychology, Developmental SC Psychology GA 995MQ UT WOS:000308012600001 ER PT J AU Park, CL Kaiser, AP Spiro, A King, DW King, LA AF Park, Crystal L. Kaiser, Anica Pless Spiro, Avron, III King, Daniel W. King, Lynda A. TI Does Wartime Captivity Affect Late-Life Mental Health? A Study of Vietnam-Era Repatriated Prisoners of War SO RESEARCH IN HUMAN DEVELOPMENT LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; FORMER PRISONERS; SOCIAL SUPPORT; FOLLOW-UP; PTSD; TRAUMA; RESILIENCE; EXPERIENCE; SCALE AB This study extended our previous analyses of predictors of well-being shortly after homecoming among U. S. Vietnam-era repatriated prisoners of war. We examined associations of demographic factors, captivity stressors, and repatriation mental health with posttraumatic stress, anxiety, and depression nearly 30 years later in 292 Vietnam-era repatriated prisoners of war. For most, symptoms were within normal limits, but a substantial minority reported clinically elevated levels. Age at capture and posttraumatic stress symptoms at repatriation predicted all three long-term mental health outcomes. Physical torture also predicted long-term posttraumatic stress symptoms. Findings highlight both long-term effects of captivity and significant capacity for resilience. C1 [Park, Crystal L.] Univ Connecticut, Dept Psychol, Storrs, CT 06269 USA. [Kaiser, Anica Pless; Spiro, Avron, III; King, Daniel W.; King, Lynda A.] Boston Univ, Boston, MA 02215 USA. [Kaiser, Anica Pless; Spiro, Avron, III; King, Daniel W.; King, Lynda A.] VA Boston Healthcare Syst, Boston, MA USA. RP Park, CL (reprint author), Univ Connecticut, Dept Psychol, U Box 1020, Storrs, CT 06269 USA. EM crystal.park@uconn.edu FU NIA NIH HHS [R24 AG039343] NR 25 TC 7 Z9 7 U1 2 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1542-7609 EI 1542-7617 J9 RES HUM DEV JI Res. Hum. Dev. PY 2012 VL 9 IS 3 SI SI BP 191 EP 209 DI 10.1080/15427609.2012.705554 PG 19 WC Psychology, Developmental SC Psychology GA 995MQ UT WOS:000308012600002 PM 22984347 ER PT J AU Kaiser, AP Spiro, A Lee, LO Stellman, JM AF Kaiser, Anica Pless Spiro, Avron, III Lee, Lewina Onyi Stellman, Jeanne Mager TI Women Vietnam Veterans: Do PTSD Symptoms Mediate Effects of Warzone Service on Health? SO RESEARCH IN HUMAN DEVELOPMENT LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; REPORTED PHYSICAL HEALTH; COMBAT EXPOSURE; AMERICAN LEGIONNAIRES; TRAUMA; FEMALE; WAR; DEPRESSION; EXPERIENCE; MILITARY AB We used regression models to assess the impact of warzone stress on physical and mental health of 975 female Vietnam veteran nurses, and whether current PTSD symptoms mediated these relations. Women's Vietnam Memorial Project members were surveyed in 1998, with analyses adjusted for age, length of military service, and current health symptoms. Findings suggest that among women nurses deployed to Vietnam, the effects of warzone stress many years earlier on current health are both direct and indirect, mediated by PTSD symptoms. The legacy of wartime deployment remains, although muted in its expression, in military nurses nearly 30 years after their return. C1 [Stellman, Jeanne Mager] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Spiro, Avron, III; Lee, Lewina Onyi] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Kaiser, Anica Pless; Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02215 USA. [Kaiser, Anica Pless; Spiro, Avron, III; Lee, Lewina Onyi] VA Boston Healthcare Syst, Boston, MA USA. RP Stellman, JM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, 600 W 168th St, New York, NY 10032 USA. EM jms13@columbia.edu FU NIA NIH HHS [R24 AG039343] NR 37 TC 2 Z9 2 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1542-7609 EI 1542-7617 J9 RES HUM DEV JI Res. Hum. Dev. PY 2012 VL 9 IS 3 SI SI BP 210 EP 228 DI 10.1080/15427609.2012.705553 PG 19 WC Psychology, Developmental SC Psychology GA 995MQ UT WOS:000308012600003 PM 22984348 ER PT J AU Jahn, AL Herman, L Schuster, J Naik, A Moye, J AF Jahn, Allison L. Herman, Levi Schuster, Jennifer Naik, Aanand Moye, Jennifer TI Distress and Resilience After Cancer in Veterans SO RESEARCH IN HUMAN DEVELOPMENT LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; BREAST-CANCER; CIVILIAN VERSION; COMBAT EXPOSURE; PROSTATE-CANCER; PTSD CHECKLIST; PRIMARY-CARE; GROWTH; SURVIVORS; LIFE AB Combat exposure and posttraumatic stress have the potential to affect distress in response to cancer, a common late-life stressor. Models of posttraumatic growth suggest that distress can produce varying avenues for resilience. A primarily male, veteran sample completed interviews regarding how combat exposure and posttraumatic stress relate to distress and growth in cancer survivors. While combat alone did not predict greater distress, combat veterans with current combat-related posttraumatic stress symptoms reported the greatest distress following cancer. These same veterans showed cancer-related growth. This is the first large-scale study examining the relationships among combat, posttraumatic stress, and emotional health following cancer. C1 [Moye, Jennifer] VA Boston Healthcare Syst, Brockton Div, Brockton, MA 02301 USA. [Jahn, Allison L.; Moye, Jennifer] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Herman, Levi; Naik, Aanand] Michael E DeBakey VAMC, Houston, TX USA. [Herman, Levi; Naik, Aanand] Baylor Coll Med, Houston, TX 77030 USA. RP Moye, J (reprint author), VA Boston Healthcare Syst, Brockton Div, 940 Belmont St, Brockton, MA 02301 USA. EM Jennifer.Moye@va.gov OI Moye, Jennifer/0000-0002-3434-347X FU RRD VA [I01 RX000104] NR 48 TC 8 Z9 9 U1 1 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1542-7609 EI 1542-7617 J9 RES HUM DEV JI Res. Hum. Dev. PY 2012 VL 9 IS 3 SI SI BP 229 EP 247 DI 10.1080/15427609.2012.705555 PG 19 WC Psychology, Developmental SC Psychology GA 995MQ UT WOS:000308012600004 PM 25774100 ER PT J AU Foroud, T Phillips, TJ AF Foroud, Tatiana Phillips, Tamara J. TI Assessing the Genetic Risk for Alcohol Use Disorders SO ALCOHOL RESEARCH-CURRENT REVIEWS LA English DT Review DE Alcohol dependence; alcoholism; genetics; genetic basis of alcoholism; genetic mapping; gene interactions; genetic technology; gene knockout technology; human studies; animal models ID UNITED-STATES; MICE; DEPENDENCE; ASSOCIATION; CONSUMPTION; PREVALENCE; EXPRESSION; AMYGDALA; ETHANOL; SAMPLE AB The past two decades have witnessed a revolution in the field of genetics which has led to a rapid evolution in the tools and techniques available for mapping genes that contribute to genetically complex disorders such as alcohol dependence. Research in humans and in animal models of human disease has provided important new information. Among the most commonly applied approaches used in human studies are family studies, case control studies, and genome-wide association studies. Animal models have been aimed at identifying genetic regions or individual genes involved in different aspects of alcoholism, using such approaches as quantitative trait locus analysis, genome sequencing, knockout animals, and other sophisticated molecular genetic techniques. All of these approaches have led to the identification of several genes that seem to influence the risk for alcohol dependence, which are being further analyzed. Newer studies, however, also are attempting to look at the genetic basis of alcoholism at the level of the entire genome, moving beyond the study of individual genes toward analyses of gene interactions and gene networks in the development of this devastating disease. C1 [Foroud, Tatiana] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46204 USA. [Phillips, Tamara J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Phillips, Tamara J.] Portland VA Med Ctr, Portland, OR USA. RP Foroud, T (reprint author), Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46204 USA. FU NIAAA NIH HHS [P60 AA010760] NR 23 TC 1 Z9 1 U1 4 U2 7 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES-CURR REV JI Alcohol Res.-Curr. Rev. PY 2012 VL 34 IS 3 BP 266 EP + PG 5 WC Substance Abuse SC Substance Abuse GA 980CU UT WOS:000306872000003 PM 23134042 ER PT J AU Hassija, CM Luterek, JA Naragon-Gainey, K Moore, SA Simpson, T AF Hassija, Christina M. Luterek, Jane A. Naragon-Gainey, Kristin Moore, Sally A. Simpson, Tracy TI Impact of emotional approach coping and hope on PTSD and depression symptoms in a trauma exposed sample of Veterans receiving outpatient VA mental health care services SO ANXIETY STRESS AND COPING LA English DT Article DE coping; hope; PTSD; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; EXPERIENTIAL AVOIDANCE; SOCIAL SUPPORT; PSYCHOLOGICAL DISTRESS; SEVERITY; VALIDATION; STRATEGIES; ANXIETY; STYLE; QUESTIONNAIRE AB The present investigation evaluates the relationship between coping style, dispositional hope, and posttraumatic stress disorder (PTSD) and depression symptom severity in a trauma-exposed Veteran sample. Specifically, we evaluated the adaptive value of emotional avoidant and approach coping strategies and perceptions of hope in a sample of 209 trauma-exposed Veterans receiving outpatient mental health care at a VA facility. Participants completed a life events questionnaire and inventories assessing coping, dispositional hope, and PTSD and depression symptom severity. Hierarchical regression analyses were conducted controlling for relevant demographic variables. Greater levels of emotional avoidance and lower levels of emotional expression were significantly associated with increased PTSD and depression symptom severity. Dispositional hope was positively associated with depression symptoms only and perceptions of hope moderated the association between emotional avoidance coping and depression symptoms. Findings highlight the value of emotional coping strategies and perceptions of hope in posttraumatic adjustment. Specifically, employing coping techniques that encourage emotional expression may promote improved adjustment among trauma-exposed individuals, while reduced perceptions of hope and the use of avoidant coping strategies may place individuals at greater risk for depression following exposure to traumatic events. C1 [Hassija, Christina M.; Luterek, Jane A.; Naragon-Gainey, Kristin; Moore, Sally A.; Simpson, Tracy] Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle Div, Seattle, WA 98126 USA. [Hassija, Christina M.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Luterek, Jane A.; Moore, Sally A.; Simpson, Tracy] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Naragon-Gainey, Kristin] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. [Moore, Sally A.] Evidence Based Treatment Ctr Seattle, Seattle, WA USA. RP Hassija, CM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle Div, 1660 S Columbian Way, Seattle, WA 98126 USA. EM Chassija@uwyo.edu RI Schueter, nicos/A-3625-2014 NR 56 TC 9 Z9 9 U1 4 U2 15 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PY 2012 VL 25 IS 5 BP 559 EP 573 DI 10.1080/10615806.2011.621948 PG 15 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA 990PN UT WOS:000307643100006 PM 22059938 ER PT J AU Antoniou, AC Kuchenbaecker, KB Soucy, P Beesley, J Chen, XQ McGuffog, L Lee, A Barrowdale, D Healey, S Sinilnikova, OM Caligo, MA Loman, N Harbst, K Lindblom, A Arver, B Rosenquist, R Karlsson, P Nathanson, K Domchek, S Rebbeck, T Jakubowska, A Lubinski, J Jaworska, K Durda, K Zlowowcka-Perlowska, E Osorio, A Duran, M Andres, R Benitez, J Hamann, U Hogervorst, FB van Os, TA Verhoef, S Meijers-Heijboer, HEJ Wijnen, J Garcia, EBG Ligtenberg, MJ Kriege, M Collee, M Ausems, MGEM Oosterwijk, JC Peock, S Frost, D Ellis, SD Platte, R Fineberg, E Evans, DG Lalloo, F Jacobs, C Eeles, R Adlard, J Davidson, R Cole, T Cook, J Paterson, J Douglas, F Brewer, C Hodgson, S Morrison, PJ Walker, L Rogers, MT Donaldson, A Dorkins, H Godwin, AK Bove, B Stoppa-Lyonnet, D Houdayer, C Buecher, B de Pauw, A Mazoyer, S Calender, A Leone, M Bressac-de Paillerets, B Caron, O Sobol, H Frenay, M Prieur, F Ferrer, SF Mortemousque, I Buys, S Daly, M Miron, A Terry, MB Hopper, JL John, EM Southey, M Goldgar, D Singer, CF Fink-Retter, A Tea, MK Kaulich, DG Hansen, TVO Nielsen, FC Barkardottir, RB Gaudet, M Kirchhoff, T Joseph, V Dutra-Clarke, A Offit, K Piedmonte, M Kirk, J Cohn, D Hurteau, J Byron, J Fiorica, J Toland, AE Montagna, M Oliani, C Imyanitov, E Isaacs, C Tihomirova, L Blanco, I Lazaro, C Teule, A Del Valle, J Gayther, SA Odunsi, K Gross, J Karlan, BY Olah, E Teo, SH Ganz, PA Beattie, MS Dorfling, CM van Rensburg, EJ Diez, O Kwong, A Schmutzler, RK Wappenschmidt, B Engel, C Meindl, A Ditsch, N Arnold, N Heidemann, S Niederacher, D Preisler-Adams, S Gadzicki, D Varon-Mateeva, R Deissler, H Gehrig, A Sutter, C Kast, K Fiebig, B Schafer, D Caldes, T de la Hoya, M Nevanlinna, H Muranen, TA Lesperance, B Spurdle, AB Neuhausen, SL Ding, YC Wang, XS Fredericksen, Z Pankratz, VS Lindor, NM Peterlongo, P Manoukian, S Peissel, B Zaffaroni, D Bonanni, B Bernard, L Dolcetti, R Papi, L Ottini, L Radice, P Greene, MH Loud, JT Andrulis, IL Ozcelik, H Mulligan, AM Glendon, G Thomassen, M Gerdes, AM Jensen, UB Skytte, AB Kruse, TA Chenevix-Trench, G Couch, FJ Simard, J Easton, DF AF Antoniou, Antonis C. Kuchenbaecker, Karoline B. Soucy, Penny Beesley, Jonathan Chen, Xiaoqing McGuffog, Lesley Lee, Andrew Barrowdale, Daniel Healey, Sue Sinilnikova, Olga M. Caligo, Maria A. Loman, Niklas Harbst, Katja Lindblom, Annika Arver, Brita Rosenquist, Richard Karlsson, Per Nathanson, Kate Domchek, Susan Rebbeck, Tim Jakubowska, Anna Lubinski, Jan Jaworska, Katarzyna Durda, Katarzyna Zlowowcka-Perlowska, Elzbieta Osorio, Ana Duran, Mercedes Andres, Raquel Benitez, Javier Hamann, Ute Hogervorst, Frans B. van Os, Theo A. Verhoef, Senno Meijers-Heijboer, Hanne E. J. Wijnen, Juul Garcia, Encarna B. Gomez Ligtenberg, Marjolijn J. Kriege, Mieke Collee, Margriet Ausems, Margreet G. E. M. Oosterwijk, Jan C. Peock, Susan Frost, Debra Ellis, Steve D. Platte, Radka Fineberg, Elena Evans, D. Gareth Lalloo, Fiona Jacobs, Chris Eeles, Ros Adlard, Julian Davidson, Rosemarie Cole, Trevor Cook, Jackie Paterson, Joan Douglas, Fiona Brewer, Carole Hodgson, Shirley Morrison, Patrick J. Walker, Lisa Rogers, Mark T. Donaldson, Alan Dorkins, Huw Godwin, Andrew K. Bove, Betsy Stoppa-Lyonnet, Dominique Houdayer, Claude Buecher, Bruno de Pauw, Antoine Mazoyer, Sylvie Calender, Alain Leone, Melanie Bressac-de Paillerets, Brigitte Caron, Olivier Sobol, Hagay Frenay, Marc Prieur, Fabienne Ferrer, Sandra Fert Mortemousque, Isabelle Buys, Saundra Daly, Mary Miron, Alexander Terry, Mary Beth Hopper, John L. John, Esther M. Southey, Melissa Goldgar, David Singer, Christian F. Fink-Retter, Anneliese Tea, Muy-Kheng Kaulich, Daphne Geschwantler Hansen, Thomas V. O. Nielsen, Finn C. Barkardottir, Rosa B. Gaudet, Mia Kirchhoff, Tomas Joseph, Vijai Dutra-Clarke, Ana Offit, Kenneth Piedmonte, Marion Kirk, Judy Cohn, David Hurteau, Jean Byron, John Fiorica, James Toland, Amanda E. Montagna, Marco Oliani, Cristina Imyanitov, Evgeny Isaacs, Claudine Tihomirova, Laima Blanco, Ignacio Lazaro, Conxi Teule, Alex Del Valle, J. Gayther, Simon A. Odunsi, Kunle Gross, Jenny Karlan, Beth Y. Olah, Edith Teo, Soo-Hwang Ganz, Patricia A. Beattie, Mary S. Dorfling, Cecelia M. van Rensburg, Elizabeth Jansen Diez, Orland Kwong, Ava Schmutzler, Rita K. Wappenschmidt, Barbara Engel, Christoph Meindl, Alfons Ditsch, Nina Arnold, Norbert Heidemann, Simone Niederacher, Dieter Preisler-Adams, Sabine Gadzicki, Dorothea Varon-Mateeva, Raymonda Deissler, Helmut Gehrig, Andrea Sutter, Christian Kast, Karin Fiebig, Britta Schaefer, Dieter Caldes, Trinidad de la Hoya, Miguel Nevanlinna, Heli Muranen, Taru A. Lesperance, Bernard Spurdle, Amanda B. Neuhausen, Susan L. Ding, Yuan C. Wang, Xianshu Fredericksen, Zachary Pankratz, Vernon S. Lindor, Noralane M. Peterlongo, Paolo Manoukian, Siranoush Peissel, Bernard Zaffaroni, Daniela Bonanni, Bernardo Bernard, Loris Dolcetti, Riccardo Papi, Laura Ottini, Laura Radice, Paolo Greene, Mark H. Loud, Jennifer T. Andrulis, Irene L. Ozcelik, Hilmi Mulligan, Anna Marie Glendon, Gord Thomassen, Mads Gerdes, Anne-Marie Jensen, Uffe B. Skytte, Anne-Bine Kruse, Torben A. Chenevix-Trench, Georgia Couch, Fergus J. Simard, Jacques Easton, Douglas F. CA CIMBA Study Collaborator SWE-BRCA Study Collaborator HEBON Study Collaborator EMBRACE Study Collaborator GEMO Study Collaborator KConFab Investigators TI Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers SO BREAST CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; HORMONE-RELATED PROTEIN; OVARIAN-CANCER; SUSCEPTIBILITY LOCI; MAMMOGRAPHIC DENSITY; GENETIC MODIFIERS; TUMOR SUBTYPES; ALLELES; CONSORTIUM; INVESTIGATORS AB Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10(-4)). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10(-5), P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df P = 0.007; rs1292011 2df P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10(-5)) and there was marginal evidence of association with ER- negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers. C1 [Antoniou, Antonis C.; Kuchenbaecker, Karoline B.; McGuffog, Lesley; Lee, Andrew; Barrowdale, Daniel; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Easton, Douglas F.; EMBRACE Study Collaborator] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England. [Soucy, Penny] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada. [Beesley, Jonathan; Chen, Xiaoqing; Healey, Sue; Spurdle, Amanda B.; Chenevix-Trench, Georgia] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia. [Sinilnikova, Olga M.] Ctr Hosp Univ Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, F-69373 Lyon, France. [Sinilnikova, Olga M.] Univ Lyon 1, INSERM, U1052, Canc Res Ctr Lyon,CNRS,UMR5286, F-69373 Lyon, France. [Caligo, Maria A.] Univ Pisa, Dept Lab Med, Sect Genet Oncol, I-56125 Pisa, Italy. [Caligo, Maria A.] Univ Hosp Pisa, I-56125 Pisa, Italy. [Loman, Niklas; Harbst, Katja; CIMBA Study Collaborator; SWE-BRCA Study Collaborator] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. [Lindblom, Annika] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden. [Arver, Brita] Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden. [Rosenquist, Richard] Uppsala Univ, Dept Genet & Pathol, Rudbeck Lab, Uppsala, Sweden. [Karlsson, Per] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. [Nathanson, Kate; Domchek, Susan; Rebbeck, Tim] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Zlowowcka-Perlowska, Elzbieta] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Durda, Katarzyna] Warsaw Med Univ, Postgrad Sch Mol Med, Warsaw, Poland. [Osorio, Ana] Spanish Natl Canc Res Ctr, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain. [Duran, Mercedes] Univ Valladolid IBGM UVA, Inst Biol & Mol Genet, Valladolid, Spain. [Andres, Raquel] Hosp Clin Univ Lozano Blesa, Oncol Unit, Zaragoza, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr, Genotyping Unit, Human Canc Genet Programme, Madrid, Spain. [Hamann, Ute] Deutsch Krebsforschungszentrum DKFZ, Heidelberg, Germany. [Hogervorst, Frans B.] Netherlands Canc Inst, Family Canc Clin, Amsterdam, Netherlands. [van Os, Theo A.] Univ Amsterdam, Acad Med Ctr, Dept Clin Genet, NL-1105 AZ Amsterdam, Netherlands. [Verhoef, Senno] Netherlands Canc Inst, Dept Clin Genet, Amsterdam, Netherlands. [Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Wijnen, Juul; Garcia, Encarna B. Gomez] MUMC, Sch Oncol & Dev Biol, GROM, Maastricht, Netherlands. [Wijnen, Juul; Garcia, Encarna B. Gomez] MUMC, Sch Oncol & Dev Biol, Dept Clin Genet, Maastricht, Netherlands. [Ligtenberg, Marjolijn J.] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Kriege, Mieke; Collee, Margriet] Erasmus Univ, Dept Clin Genet, Med Ctr, Family Canc Clin, NL-3000 DR Rotterdam, Netherlands. [Ausems, Margreet G. E. M.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3508 AB Utrecht, Netherlands. [Oosterwijk, Jan C.] Univ Groningen, Dept Genet, Univ Med Ctr, Groningen, Netherlands. [Evans, D. Gareth; Lalloo, Fiona] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Jacobs, Chris] Guys & St Thomas NHS Fdn Trust, London, England. [Eeles, Ros] Royal Marsden NHS Fdn Trust, London, England. [Adlard, Julian] Yorkshire Reg Genet Serv, Leeds, W Yorkshire, England. [Davidson, Rosemarie] Yorkhill Hosp, Ferguson Smith Ctr Clin Genet, Glasgow, Lanark, Scotland. [Cole, Trevor] Birmingham Womens Hosp Healthcare NHS Trust, W Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Cook, Jackie] Sheffield Childrens Hosp, Sheffield Clin Genet Serv, Sheffield, S Yorkshire, England. [Paterson, Joan] Addenbrookes Hosp, E Anglian Reg Genet Serv, Dept Clin Genet, Cambridge, England. [Douglas, Fiona] Newcastle Tyne Hosp NHS Trust, Ctr Life, Inst Med Genet, Newcastle Upon Tyne, Tyne & Wear, England. [Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX2 5DW, Devon, England. [Hodgson, Shirley] Univ London, Med Genet Unit, London WC1E 7HU, England. [Morrison, Patrick J.] Queens Univ Belfast, Dept Med Genet, Belfast, Antrim, North Ireland. [Morrison, Patrick J.] Belfast Hlth & Social Care Trust, No Ireland Reg Genet Ctr, Belfast, Antrim, North Ireland. [Walker, Lisa] Churchill Hosp, Oxford Reg Genet Serv, Oxford OX3 7LJ, England. [Rogers, Mark T.] Univ Wales Hosp, All Wales Med Genet Serv, Cardiff CF4 4XW, S Glam, Wales. [Donaldson, Alan] St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England. [Dorkins, Huw] Kennedy Galton Ctr, NW Thames Reg Genet Serv, Harrow, Middx, England. [Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Bove, Betsy] Fox Chase Canc Ctr, Clin Mol Genet Lab, Philadelphia, PA 19111 USA. [Stoppa-Lyonnet, Dominique; Houdayer, Claude; Buecher, Bruno; de Pauw, Antoine] Inst Curie, Serv Genet Oncol, Paris, France. [Stoppa-Lyonnet, Dominique] Inst Curie, INSERM, U830, Paris, France. [Stoppa-Lyonnet, Dominique] Univ Paris 05, Fac Med, Paris, France. [Houdayer, Claude] Univ Paris 05, Fac Pharm, Paris, France. [Mazoyer, Sylvie] Univ Lyon 1, INSERM, U1052, Ctr Rech Cancerol Lyon,CNRS,UMR5286, F-69365 Lyon, France. [Calender, Alain; Leone, Melanie] Hosp Civils Lyon, Ctr Leon Berard, Unite Mixte Genet Constitut Canc Frequents, Lyon, France. [Bressac-de Paillerets, Brigitte] Inst Cancerol Gustave Roussy, Serv Genet, Villejuif, France. [Bressac-de Paillerets, Brigitte] INSERM, U946, Fdn Jean Dausset, Paris, France. [Caron, Olivier] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [Sobol, Hagay] Univ Aix Marseille 2, Inst J Paoli I Calmettes, Dept Oncol Genet Prevent & Depistage, INSERM CIC P9502, F-13284 Marseille 07, France. [Frenay, Marc] Ctr Antoine Lacassagne, F-06054 Nice, France. [Prieur, Fabienne] Ctr Hosp Univ St Etienne, Serv Genet Clin Chromosom & Mol, St Etienne, France. [Ferrer, Sandra Fert] Hotel Dieu Ctr Hosp, Lab Genet Chromosom, Chambery, France. [Mortemousque, Isabelle] Ctr Hosp Univ Bretonneau, Serv Genet, Tours, France. [Buys, Saundra] Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Daly, Mary] Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. [Miron, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02210 USA. [Miron, Alexander] Harvard Univ, Dept Surg, Sch Med, Boston, MA 02210 USA. [Terry, Mary Beth] Columbia Univ, Dept Epidemiol, New York, NY USA. [Hopper, John L.] Univ Melbourne, Ctr Mol Environm Genet & Analyt MEGA Epidemiol, Melbourne Sch Populat Hlth, Melbourne, Vic 3010, Australia. [John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA 94538 USA. [Southey, Melissa] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. [Goldgar, David] Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT 84132 USA. [Singer, Christian F.; Fink-Retter, Anneliese; Tea, Muy-Kheng; Kaulich, Daphne Geschwantler] Med Univ Vienna, Ctr Comprehens Canc, Vienna, Austria. [Singer, Christian F.; Fink-Retter, Anneliese; Tea, Muy-Kheng; Kaulich, Daphne Geschwantler] Med Univ Vienna, Dept OB GYN, Vienna, Austria. [Hansen, Thomas V. O.; Nielsen, Finn C.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark. [Barkardottir, Rosa B.] Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland. [Barkardottir, Rosa B.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Gaudet, Mia] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Kirchhoff, Tomas] NYU, Sch Med, Inst Canc, Dept Environm Med, New York, NY USA. [Joseph, Vijai; Dutra-Clarke, Ana; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Canc Genet Lab, New York, NY 10021 USA. [Piedmonte, Marion] Roswell Pk Canc Inst, Stat & Data Ctr, Buffalo, NY 14263 USA. [Kirk, Judy] Westmead Hosp, Australia New Zealand ANZGOG, Sydney, NSW, Australia. [Cohn, David] Ohio State Univ, Columbus Canc Council, Columbus, OH 43210 USA. [Hurteau, Jean] Univ Chicago, Chicago, IL 60637 USA. [Byron, John] Univ N Carolina, So Pines Womens Hlth Ctr PC, Chapel Hill, NC USA. [Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Immunol & Med Genet, Columbus, OH 43210 USA. [Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Columbus, OH 43210 USA. [Montagna, Marco] Ist Oncol Veneto IOV IRCCS, Immunol & Mol Oncol Unit, Padua, Italy. [Oliani, Cristina] ULSS5 Ovest, UOC Oncol, Vicentino, Italy. [Imyanitov, Evgeny] N N Petrov Inst Oncol, Mol Oncol Lab, St Petersburg, Russia. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Gross, Jenny; Karlan, Beth Y.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary. [Teo, Soo-Hwang] Sime Darby Med Ctr, Canc Res Initiat Fdn, Petaling Jaya, Malaysia. [Teo, Soo-Hwang] Univ Malaya, Med Ctr, Canc Res Inst, Kuala Lumpur, Malaysia. [Ganz, Patricia A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Beattie, Mary S.] Univ Calif San Francisco, UCSF Canc Risk Program, San Francisco, CA 94143 USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Beattie, Mary S.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Dorfling, Cecelia M.; van Rensburg, Elizabeth Jansen] Univ Pretoria, Dept Genet, Canc Genet Lab, ZA-0002 Pretoria, South Africa. [Diez, Orland] Vall dHebron Univ Hosp, Oncogenet Lab, Vall dHebron Inst Oncol VHIO, Barcelona, Spain. [Kwong, Ava] Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China. [Kwong, Ava] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Kwong, Ava] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong, Hong Kong, Peoples R China. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany. [Schmutzler, Rita K.; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Integrated Oncol CIO, Cologne, Germany. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. [Meindl, Alfons] Tech Univ Munich, Klinikum Rechts Isar, Div Tumor Genet, Dept Obstet & Gynaecol, D-8000 Munich, Germany. [Ditsch, Nina] Univ Munich, Dept Obstet & Gynaecol, D-80539 Munich, Germany. [Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, D-24098 Kiel, Germany. [Heidemann, Simone] Univ Kiel, Univ Hosp Schleswig Holstein, Inst Human Genet, D-24098 Kiel, Germany. [Niederacher, Dieter] Univ Dusseldorf, Univ Hosp Dusseldorf, Dept Obstet & Gynaecol, Dusseldorf, Germany. [Preisler-Adams, Sabine] Univ Munster, Inst Human Genet, D-4400 Munster, Germany. [Gadzicki, Dorothea] Hannover Med Sch, Inst Cell & Mol Pathol, D-3000 Hannover, Germany. [Varon-Mateeva, Raymonda] Charite, Inst Human Genet, Campus Virchov Klinikum, Berlin, Germany. [Deissler, Helmut] Univ Hosp Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Gehrig, Andrea] Univ Wurzburg, Dept Med Genet, Inst Human Genet, Ctr Familial Breast & Ovarian Canc, D-97070 Wurzburg, Germany. [Sutter, Christian] Univ Heidelberg Hosp, Dept Med Genet, Inst Human Genet, Heidelberg, Germany. [Kast, Karin] Tech Univ Dresden, Dept Obstet & Gynaecol, Univ Hosp Carl Gustav Carus, Dresden, Germany. [Fiebig, Britta] Univ Regensburg, Inst Human Genet, D-8400 Regensburg, Germany. [Schaefer, Dieter] Univ Hosp Frankfurt, Inst Human Genet, Frankfurt, Germany. [Schaefer, Dieter; Caldes, Trinidad; de la Hoya, Miguel] Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain. [Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Dept Obstet & Gynecol, Helsinki 00029, Finland. [Nevanlinna, Heli; Muranen, Taru A.] Helsinki Univ Cent Hosp, Biomedicum Helsinki, Helsinki 00029, Finland. [Lesperance, Bernard] Univ Montreal, Fac Med Med & Med Specialties, Montreal, PQ, Canada. [Lesperance, Bernard] Hop Sacre Coeur, Hematooncol Serv, Montreal, PQ H4J 1C5, Canada. [KConFab Investigators] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Neuhausen, Susan L.; Ding, Yuan C.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA. [Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Fredericksen, Zachary; Pankratz, Vernon S.] Mayo Clin, Dept Med Genet, Rochester, MN USA. [Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Peterlongo, Paolo; Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predicted Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy. [Peterlongo, Paolo; Radice, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy. [Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela] Fdn Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Med Genet, Milan, Italy. [Bonanni, Bernardo] Ist Europeo Oncol IEO, Div Canc Prevent & Genet, Milan, Italy. [Bernard, Loris] Ist Europeo Oncol, Dept Expt Oncol, Milan, Italy. [Bernard, Loris] Consortium Genom Technol Cogentech, Milan, Italy. [Dolcetti, Riccardo] IRCCS, Ctr Riferimento Oncol, Canc Bioimmunotherapy Unit, Aviano, PN, Italy. [Papi, Laura] Univ Florence, Dept Clin Physiopathol, Med Genet Unit, Florence, Italy. [Ottini, Laura] Univ Roma La Sapienza, Dept Mol Med, Rome, Italy. [Greene, Mark H.; Loud, Jennifer T.] NCI, Clin Genet Branch, DCEG, Rockville, MD 20852 USA. [Andrulis, Irene L.; Ozcelik, Hilmi] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Canc Care Ontario, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Andrulis, Irene L.] Univ Toronto, Canc Care Ontario, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Dept Lab Med, Toronto, ON M5B 1W8, Canada. [Glendon, Gord] Ontario Canc Genet Network, Toronto, ON, Canada. [Thomassen, Mads; Kruse, Torben A.] Odense Univ Hosp, Dept Clin Genet, Odense, Denmark. [Gerdes, Anne-Marie] Rigshosp, Dept Clin Genet, Copenhagen, Denmark. [Gerdes, Anne-Marie] Univ Copenhagen, DK-1168 Copenhagen, Denmark. [Jensen, Uffe B.] Skejby Hosp, Dept Clin Genet, Aarhus, Denmark. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Simard, Jacques] Ctr Hosp Univ Quebec, Canc Genom Lab, Quebec City, PQ, Canada. [Simard, Jacques] Univ Laval, Fac Med, Canada Res Chair Oncogenet, Dept Mol Med, Quebec City, PQ G1K 7P4, Canada. RP Antoniou, AC (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England. EM antonis@srl.cam.ac.uk RI del Valle, Jesus/I-2527-2015; Jakubowska, Anna/O-8050-2014; Dolcetti, Riccardo/O-3832-2015; Ligtenberg, Marjolijn/N-9666-2013; Peissel, Bernard/E-8187-2017; Arnold, Norbert/E-3012-2010; montagna, marco/E-2225-2012; Andrulis, Irene/E-7267-2013; Toland, Amanda/E-4202-2011; Joseph, Vijai/J-9158-2013; Radice, Paolo/O-3119-2013; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Blanco, Ignacio/D-2565-2013; Ditsch, Nina/F-6267-2014; Oosterwijk, Jan C./G-5770-2011; Teo, Soo-hwang/H-2353-2014; Osorio, Ana/I-4324-2014; Bernard, Loris/K-5953-2014 OI del Valle, Jesus/0000-0003-3607-7045; Muranen, Taru/0000-0002-5895-1808; Nevanlinna, Heli/0000-0002-0916-2976; Kirchhoff, Tomas/0000-0002-9055-2364; Jacobs, Chris/0000-0002-9557-9080; Evans, Gareth/0000-0002-8482-5784; Dolcetti, Riccardo/0000-0003-1625-9853; Ligtenberg, Marjolijn/0000-0003-1290-1474; Peissel, Bernard/0000-0001-9233-3571; Eeles, Rosalind/0000-0002-3698-6241; Nathanson, Katherine/0000-0002-6740-0901; Barrowdale, Daniel/0000-0003-1661-3939; Arnold, Norbert/0000-0003-4523-8808; montagna, marco/0000-0002-4929-2150; Joseph, Vijai/0000-0002-7933-151X; Blanco, Ignacio/0000-0002-7414-7481; Osorio, Ana/0000-0001-8124-3984; FU Cancer Research UK [C12292/A11174, C1287/A10118, C1287/A11990, C5047/A8385]; European Community's Seventh Framework Programme [223175, HEALTH-F2-2009-223175]; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Canadian Breast Cancer Research Alliance [019511]; NIH grant [CA128978]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; U.S. Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Komen Foundation; European Social Fund [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Cancer Association of South Africa; National Cancer Institute, National Institutes of Health [RFA-CA-06-503]; Breast Cancer Family Registry (BCFR) and Principal Investigators; Cancer Care Ontario [U01 CA69467]; Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01 CA69631]; Huntsman Cancer Institute [U01 CA69446]; Cancer Prevention Institute of California (formerly the Northern California Cancer Center) [U01 CA69417]; University of Melbourne [U01 CA69638]; Research Triangle Institute Informatics Support Center [N02PC45022-46]; Mutua Madrile a Foundation; Red de Investigacion en Cancer [RD06/0020/1160]; Spanish Ministry of Science and Innovation [FIS PI08 1120, SAF201020493]; NEYE foundation; DKFZ; NIHR grant; Familial Cancer Registry; Tissue Culture Shared Registry at Georgetown University (NIH/NCI) [P30-CA051008]; Cancer Genetics Network [HHSN261200744000C]; Swing Fore the Cure; National Cancer Institute; GOG Tissue Bank [CA 27469]; GOG Statistical and Data Center [CA 37517, CA 101165]; GOG's Cancer Prevention and Control Committee; intramural (Clinical Genetics Branch, DCEG) NCI program; extramural (Community Oncology and Prevention Trials Program - COPTRG) NCI program; Instituto de Salud Carlos III [RD06/0020/0021]; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; ZonMW [91109024]; Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Asociacion Espanola Contra el Cancer; Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute; Autonomous Government of Catalonia; Icelandic Association "Walking for Breast Cancer Research"; Landspitali University Hospital Research Fund; Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR); "Ministero della Salute" ("Progetto Tumouri Femminili) [RFPS 2006-5-341353, ACC2/R6.9]; NHMRC; National Breast Cancer Foundation; Cancer Australia [628333]; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria; Cancer Councils of New South Wales, Tasmania; Cancer Councils of New South Wales, South Australia; Cancer Foundation of Western Australia; NHMRC Senior Research Fellowship; Intramural Research Program of the US National Cancer Institute at the National Institutes of Health; Westat, Inc, Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Russian Federation for Basic Research [10-04-92601, 10-04-92110, 11-04-00227]; Federal Agency for Science and Innovations [16.512.11.2237]; Royal Society International Joint grant [JP090615]; Ellen Li Charitable Foundation; Norwegian EEA Financial Mechanism [HU0115/NA/2008-3/P-9]; Hungarian Research Grant KTIA-OTKA [CK-80745]; Ohio State University Comprehensive Cancer Center; Cancer Care Ontario; "CIHR Team in Familial Risks of Breast Cancer" program; US National Cancer Institute; National Institutes of Health under RFA [CA-06-503]; Breast Cancer Family Registry (BCFR); Principal Investigators; National Institutes of Health [R01 CA74415]; Morris and Horowitz Families Endowment; CRUK; Eileen Stein Jacoby Fund while at FCCC; University of Kansas Cancer Center; Kansas Bioscience Authority Eminent Scholar Program; American Cancer Society Clinical Research Professorship [SIOP-06-258-COUN]; [SCIIIRETIC RD06/0020/1051]; [PI10/01422]; [PI10/31488]; [2009SGR290]; [U01CA69631]; [5U01CA113916] FX This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175), from the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and by the Canadian Breast Cancer Research Alliance-grant #019511. This research was also supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341) and grants from the Breast Cancer Research Foundation and the Komen Foundation for the Cure. ACA is a CR-UK Senior Cancer Research Fellow, DFE is CR-UK Principal Research Fellow, GCT is a NHMRC Senior Principal Research Fellow, J.S. is Chairholder of the Canada Research Chair in Oncogenetics.; Research and Study Centre and Ramunas Janavicius (Vilnius University Hospital Santariskiu Clinics, Lithuania) for data and DNA samples for BFBOCC. The work was supported in part by a grant from the European Social Fund Nr. 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016.; BMBSA was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg.; This work was supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (formerly the Northern California Cancer Center) (U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). Samples from the FCCC, HCI and CPIC were processed and distributed by the Coriell Institute for Medical Research. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR.; The research leading to these results has been partially funded by Mutua Madrile a Foundation, "Red de Investigacion en Cancer RD06/0020/1160" and Spanish Ministry of Science and Innovation (FIS PI08 1120 and SAF201020493).; We would like to thank Bent Ejlertsen for clinical data and acknowledge the NEYE foundation for financial support.; The DKFZ study was supported by the DKFZ.; Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE) Douglas F. Easton is the PI of the study. EMBRACE Collaborating Centres are: Coordinating Centre, Cambridge: Susan Peock, Debra Frost, Steve D. Ellis, Elena Fineberg, Radka Platte, Clare Oliver. North of Scotland Regional Genetics Service, Aberdeen: Zosia Miedzybrodzka, Helen Gregory. Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison, Lisa Jeffers. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Kai-ren Ong, Jonathan Hoffman. South West Regional Genetics Service, Bristol: Alan Donaldson, Margaret James. East Anglian Regional Genetics Service, Cambridge: Joan Paterson, Sarah Downing, Amy Taylor. Medical Genetics Services for Wales, Cardiff: Alexandra Murray, Mark T. Rogers, Emma McCann. St James's Hospital, Dublin and National Centre for Medical Genetics, Dublin: M. John Kennedy, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous, Sarah Drummond. Peninsula Clinical Genetics Service, Exeter: Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman, Kathryn Hill. West of Scotland Regional Genetics Service, Glasgow: Rosemarie Davidson, Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson, Eshika Haque, Ed Tobias, Alexis Duncan. South East Thames Regional Genetics Service, Guy's Hospital London: Louise Izatt, Chris Jacobs, Caroline Langman. North West Thames Regional Genetics Service, Harrow: Huw Dorkins. Leicestershire Clinical Genetics Service, Leicester: Julian Barwell. Yorkshire Regional Genetics Service, Leeds: Julian Adlard, Gemma Serra-Feliu. Cheshire & Merseyside Clinical Genetics Service, Liverpool: Ian Ellis, Catherine Houghton. Manchester Regional Genetics Service, Manchester: D Gareth Evans, Fiona Lalloo, Jane Taylor. North East Thames Regional Genetics Service, NE Thames, London: Lucy Side, Alison Male, Cheryl Berlin. Nottingham Centre for Medical Genetics, Nottingham: Jacqueline Eason, Rebecca Collier. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh Claber, Irene Jobson. Oxford Regional Genetics Service, Oxford: Lisa Walker, Diane McLeod, Dorothy Halliday, Sarah Durell, Barbara Stayner. The Institute of Cancer Research and Royal Marsden NHS Foundation Trust: Ros Eeles, Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Elizabeth Page, Audrey Ardern- Jones, Kelly Kohut, Jennifer Wiggins, Elena Castro, Anita Mitra, Lisa Robertson. North Trent Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell, Cathryn Bardsley. South West Thames Regional Genetics Service, London: Shirley Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester, Charlotte Eddy, Vishakha Tripathi, Virginia Attard. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton: Diana Eccles, Anneke Lucassen, Gillian Crawford, Donna McBride, Sarah Smalley. EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles is supported by Cancer Research UK Grant C5047/A8385.; CI received support from the Familial Cancer Registry and the Tissue Culture Shared Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C), and Swing Fore the Cure.; This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office and the GOG Tissue Bank (CA 27469), and to the GOG Statistical and Data Center (CA 37517 and CA 101165). We thank the investigators of the Australia New Zealand Gynaecological Oncology Group (ANZGOG). GOG's participation was sponsored by GOG's Cancer Prevention and Control Committee, and supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program - COPTRG) NCI programs.; The HCSC study was partially supported by Instituto de Salud Carlos III; RD06/0020/0021. We wish to thank Dr. Pedro Perez-Segura and Dr. Atocha Romero for their contribution to this study.; HEBON Collaborating Centres: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: F.B.L. Hogervorst, S. Verhoef, M. Verheus, L.J. van `t Veer, F.E. van Leeuwen, M.A. Rookus; Erasmus Medical Center, Rotterdam, NL: M. Collee, A.M.W. van den Ouweland, A. Jager, M.J. Hooning, M.M.A. TilanusLinthorst, C. Seynaeve; Leiden University Medical Center, NL, Leiden: C.J. van Asperen, J.T. Wijnen, M.P. Vreeswijk, R.A. Tollenaar, P. Devilee; Radboud University Nijmegen Medical Center, Nijmegen, NL: M.J. Ligtenberg, N. Hoogerbrugge; University Medical Center Utrecht, Utrecht, NL: M.G. Ausems, R.B. van der Luijt; Amsterdam Medical Center, NL: C.M. Aalfs, T.A. van Os; VU University Medical Center, Amsterdam, NL: J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital Maastricht, Maastricht, NL: E.B. GomezGarcia, C.E. van Roozendaal, Marinus J. Blok, B. Caanen; University Medical Center Groningen University, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits; The Netherlands Foundation for the detection of hereditary tumours, Leiden, NL: H.F. Vasen. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756 and the ZonMW grant 91109024.; HEBCS acknowledge Drs. Kristiina Aittomaki, Kirsimari Aaltonen and Carl Blomqvist and Tuomas Heikkinen and research nurse Irja Erkkil for their help with the patient data and samples. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (132473), the Finnish Cancer Society, and the Sigrid Juselius Foundation.; Contract grant sponsor: Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, PI10/01422, PI10/31488 and 2009SGR290.; The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund.; This study was supported by Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) and "Ministero della Salute" ("Progetto Tumouri Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9"); We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded 2001-2009 by NHMRC and currently by the National Breast Cancer Foundation and Cancer Australia #628333) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. ABS is funded by an NHMRC Senior Research Fellowship.; The research of Drs. Greene and Loud was supported by the Intramural Research Program of the US National Cancer Institute at the National Institutes of Health, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD.; This work has been supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227) the Federal Agency for Science and Innovations (contract 16.512.11.2237) and through a Royal Society International Joint grant (JP090615).; The Hong Kong Hereditary Breast Cancer Family Registry thank Dr. Ellen Li Charitable Foundation for their support; The study was supported by Norwegian EEA Financial Mechanism (HU0115/NA/2008-3/P-9) and by Hungarian Research Grant KTIA-OTKA (CK-80745).; Leigha Senter and Kevin Sweet were instrumental in accrual of study participants, ascertainment of medical records and database management. We thank the Human Genetics Sample Bank for preparation of samples. This study was supported by the Ohio State University Comprehensive Cancer Center.; This work was supported by Cancer Care Ontario, the "CIHR Team in Familial Risks of Breast Cancer" program, and the US National Cancer Institute, National Institutes of Health under RFA #CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. We wish to thank Teresa Selander, Nayana Weerasooriya and members of the Ontario Cancer Genetics Network for their contributions to the study.; The study was supported by the National Institutes of Health (R01 CA74415 to SLN)) and the Morris and Horowitz Families Endowment.; UKFOCR was supported by a project grant from CRUK to Paul Pharoah. We thank Paul Pharoah, Susan Ramus, Carole Pye, Patricia Harrington and Eva Wozniak for their contributions towards the UKFOCR. We would like to acknowledge the Roswell Park Alliance Foundation for their continued support of the Gilda Radner Ovarian Family Cancer Registry. GRFOCR would like to acknowledge Kirsten Moysich and Lara Sucheston (Department of Cancer Prevention and Control).; We thank Ms. JoEllen Weaver for her help collecting patient data and samples. AKG was funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund while at FCCC. The author acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. AKG is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor.; This research was supported by the Breast Cancer Research Foundation (to KLN) and the Komen Foundation for the Cure (to SMD).; This work is supported by funding from the American Cancer Society Clinical Research Professorship (SIOP-06-258-COUN). NR 39 TC 38 Z9 38 U1 3 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 1 AR R33 DI 10.1186/bcr3121 PG 18 WC Oncology SC Oncology GA 987UU UT WOS:000307444100042 PM 22348646 ER PT J AU Hawkins, OE Richmond, A AF Hawkins, Oriana E. Richmond, Ann TI The dynamic yin-yang interaction of CXCR4 and CXCR7 in breast cancer metastasis SO BREAST CANCER RESEARCH LA English DT Editorial Material ID MIGRATION AB The contribution of CXCR7 to the tumor microenvironment has introduced a new level of complexity to CXCL12 signaling in breast cancer. In the previous issue of Breast Cancer Research, Hernandez and colleagues delineate the roles of CXCR4 and CXCR7 in tumor invasion and metastasis. The authors demonstrate that co-expression of CXCR7 and CXCR4 results in inhibition of CXCL12-mediated invasion, reduced intravasation of tumor cells into the vasculature, and fewer lung metastases compared with parental tumors. The results of this study suggest the combination of small molecule inhibitors of CXCR4 and CXCR7 could dramatically reduce invasion, intravasation, and metastasis and could be highly beneficial for the treatment of invasive breast cancer. C1 [Hawkins, Oriana E.; Richmond, Ann] Vanderbilt Univ, Dept Canc Biol, Sch Med, US Dept Vet Affairs, Nashville, TN 37232 USA. RP Richmond, A (reprint author), Vanderbilt Univ, Dept Canc Biol, Sch Med, US Dept Vet Affairs, 2220 Pierce Ave,771 Preston Res Bldg, Nashville, TN 37232 USA. EM Ann.richmond@vanderbilt.edu RI Hawkins, Oriana/F-9801-2013 FU NCI NIH HHS [R01 CA034590, U54 CA163069] NR 8 TC 12 Z9 12 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X J9 BREAST CANCER RES JI Breast Cancer Res. PY 2012 VL 14 IS 1 AR 103 DI 10.1186/bcr3092 PG 3 WC Oncology SC Oncology GA 987UU UT WOS:000307444100003 PM 22293321 ER PT J AU Tsai, TH Zhou, C Lee, HC Tao, YK Ahsen, OO Figueiredo, M Adler, DC Schmitt, JM Huang, Q Fujimoto, JG Mashimo, H AF Tsai, Tsung-Han Zhou, Chao Lee, Hsiang-Chieh Tao, Yuankai K. Ahsen, Osman O. Figueiredo, Marisa Adler, Desmond C. Schmitt, Joseph M. Huang, Qin Fujimoto, James G. Mashimo, Hiroshi TI Comparison of Tissue Architectural Changes between Radiofrequency Ablation and Cryospray Ablation in Barrett's Esophagus Using Endoscopic Three-Dimensional Optical Coherence Tomography SO GASTROENTEROLOGY RESEARCH AND PRACTICE LA English DT Article ID SPRAY CRYOTHERAPY; BURIED GLANDS; THERAPY; DYSPLASIA; ENDOMICROSCOPY; RESECTION; EFFICACY; SAFETY AB Two main nonsurgical endoscopic approaches for ablating dysplastic and early cancer lesions in the esophagus have gained popularity, namely, radiofrequency ablation (RFA) and cryospray ablation (CSA). We report a uniquely suited endoscopic and near-microscopic imaging modality, three-dimensional (3D) optical coherence tomography (OCT), to assess and compare the esophagus immediately after RFA and CSA. The maximum depths of architectural changes were measured and compared between the two treatment groups. RFA was observed to induce 230 similar to 260 mu m depth of architectural changes after each set of ablations over a particular region, while CSA was observed to induce edema-like spongiform changes to similar to 640 mu m depth within the ablated field. The ability to obtain micron-scale depth-resolved images of tissue structural changes following different ablation therapies makes 3D-OCT an ideal tool to assess treatment efficacy. Such information could be potentially used to provide real-time feedback for treatment dosing and to identify regions that need further retreatment. C1 [Figueiredo, Marisa; Huang, Qin; Mashimo, Hiroshi] VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA 02130 USA. [Tsai, Tsung-Han; Zhou, Chao; Lee, Hsiang-Chieh; Tao, Yuankai K.; Ahsen, Osman O.; Fujimoto, James G.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Tsai, Tsung-Han; Zhou, Chao; Lee, Hsiang-Chieh; Tao, Yuankai K.; Ahsen, Osman O.; Fujimoto, James G.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Figueiredo, Marisa; Huang, Qin; Mashimo, Hiroshi] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Adler, Desmond C.; Schmitt, Joseph M.] St Jude Med Inc, LightLab Imaging Inc, Westford, MA 01886 USA. RP Mashimo, H (reprint author), VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA 02130 USA. EM hmashimo@hms.harvard.edu RI Zhou, Chao/A-1327-2007; Ahsen, Osman/K-4524-2015; OI Ahsen, Osman/0000-0003-4811-3429; Tsai, Tsung-Han/0000-0002-2306-2269 FU MIT/CIMIT Medical Engineering Fellowship; National Science Council of Taiwan; VA Boston Healthcare System; NIH [R01-CA75289-15, K99-EB010071-01A1, R44-CA101067-06]; Air Force Office of Scientific Research [FA9550-10-1-0063]; Medical Free Electron Laser Program [FA9550-10-1-0551] FX The authors acknowledge the facility support from VA Boston Healthcare System. This work was supported by the MIT/CIMIT Medical Engineering Fellowship and Taiwan Merit Scholarship from the National Science Council of Taiwan (THT), the VA Boston Healthcare System and NIH Grants R01-CA75289-15 (J. G. Fujimoto and H. Mashimo), K99-EB010071-01A1 (C. Zhou) and R44-CA101067-06 (J. G. Fujimoto), Air Force Office of Scientific Research Contract FA9550-10-1-0063 (J. G. Fujimoto), and Medical Free Electron Laser Program Contract FA9550-10-1-0551 (J. G. Fujimoto). NR 33 TC 5 Z9 5 U1 5 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-6121 J9 GASTROENT RES PRACT JI Gastroenterol. Res. Pract. PY 2012 AR 684832 DI 10.1155/2012/684832 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 989YH UT WOS:000307596900001 ER PT J AU Ho, L Zhao, W Dams-O'Connor, K Tang, CY Gordon, W Peskind, ER Yemul, S Haroutunian, V Pasinetti, GM AF Ho, Lap Zhao, Wei Dams-O'Connor, Kristen Tang, Cheuk Y. Gordon, Wayne Peskind, Elaine R. Yemul, Shrishailam Haroutunian, Vahram Pasinetti, Giulio Maria TI Elevated Plasma MCP-1 Concentration Following Traumatic Brain Injury as a Potential "Predisposition" Factor Associated with an Increased Risk for Subsequent Development of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; biomarker; long-term clinical TBI phenotypes; mild cognitive impairment; monocyte chemotactic protein-1; plasma; traumatic brain injury ID DIFFUSE AXONAL INJURY; MULTIPLE-SCLEROSIS; EXPRESSION; CHEMOKINES; PROTEIN; MECHANISMS; RAT; IDENTIFICATION; LOCALIZATION; INFLAMMATION AB We explored whether changes in the expression profile of peripheral blood plasma proteins may provide a clinical, readily accessible "window" into the brain, reflecting molecular alterations following traumatic brain injury (TBI) that might contribute to TBI complications. We recruited fourteen TBI and ten control civilian participants for the study, and also analyzed banked plasma specimens from 20 veterans with TBI and 20 control cases. Using antibody arrays and ELISA assays, we explored differentially-regulated protein species in the plasma of TBI compared to healthy controls from the two independent cohorts. We found three protein biomarker species, monocyte chemotactic protein-1 (MCP-1), insulin-like growth factor-binding protein-3, and epidermal growth factor receptor, that are differentially regulated in plasma specimens of the TBI cases. A three-biomarker panel using all three proteins provides the best potential criterion for separating TBI and control cases. Plasma MCP-1 contents are correlated with the severity of TBI and the index of compromised axonal fiber integrity in the frontal cortex. Based on these findings, we evaluated postmortem brain specimens from 7 mild cognitive impairment (MCI) and 7 neurologically normal cases. We found elevated MCP-1 expression in the frontal cortex of MCI cases that are at high risk for developing Alzheimer's disease. Our findings suggest that additional application of the three-biomarker panel to current diagnostic criteria may lead to improved TBI detection and more sensitive outcome measures for clinical trials. Induction of MCP-1 in response to TBI might be a potential predisposing factor that may increase the risk for development of Alzheimer's disease. C1 [Ho, Lap; Zhao, Wei; Yemul, Shrishailam; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Dams-O'Connor, Kristen; Gordon, Wayne] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. [Tang, Cheuk Y.; Haroutunian, Vahram] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY USA. [Peskind, Elaine R.] Univ Washington, Sch Med, VA NW Network Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. [Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1468 Madison Ave,Annenberg Bldg,Room 20-02, New York, NY 10029 USA. EM Giulio.Pasinetti@mssm.edu FU UW Alzheimer's Disease Research Center [P50AG05136]; Pacific Northwest Udall Center [P50NS062684]; ADRC [AG05138, PPG AG02219]; Department of Veterans Affairs Rehabilitation Research and Development; National Center for Research Resources (NCRR); National Institutes of Health (NIH) [UL1RR029887] FX This study was supported by UW Alzheimer's Disease Research Center (P50AG05136), Pacific Northwest Udall Center (P50NS062684), the ADRC (AG05138 and PPG AG02219), the Department of Veterans Affairs Rehabilitation Research and Development, and the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) (UL1RR029887). NR 72 TC 17 Z9 18 U1 2 U2 13 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 31 IS 2 BP 301 EP 313 DI 10.3233/JAD-2012-120598 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 986WS UT WOS:000307377300007 PM 22543850 ER PT J AU Cholerton, B Baker, LD Trittschuh, EH Crane, PK Larson, EB Arbuckle, M Saucedo, HH McCurry, SM Bowen, JD McCormick, WC Craft, S AF Cholerton, Brenna Baker, Laura D. Trittschuh, Emily H. Crane, Paul K. Larson, Eric B. Arbuckle, Matthew Saucedo, Hector Hernandez McCurry, Susan M. Bowen, James D. McCormick, Wayne C. Craft, Suzanne TI Insulin and Sex Interactions in Older Adults with Mild Cognitive Impairment SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Age-related memory disorders; aging; Alzheimer's disease; cognition; dementia; hyperinsulinemia; insulin; vascular ID AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E GENOTYPE; NORMAL GLUCOSE-TOLERANCE; HONOLULU HEART PROGRAM; IQ-ADJUSTED NORMS; ALZHEIMERS-DISEASE; CARDIOVASCULAR-DISEASE; DEGRADING ENZYME; DIABETES-MELLITUS; RISK-FACTORS AB Alzheimer's disease (AD) and other dementias are likely preceded by a protracted preclinical state. Thus, identification of biomarkers that signal potential points of intervention during this prodromal phase (during which patients are largely able to compensate for their cognitive deficits) is of paramount importance. Insulin is a pancreatic hormone with potent central nervous system effects, and insulin dysregulation has been implicated in the pathogenesis of both AD and vascular dementia. The aim of the current study was to determine whether circulating insulin differs as a function of mild cognitive impairment (MCI) diagnosis, and whether this relationship is mediated by sex and apolipoprotein E (APOE) genotype. A sample of 549 nondemented participants aged 65 and over from the Adult Changes in Thought community-based cohort underwent cognitive testing and blood draw to determine fasting levels of plasma insulin. Subjects were categorized as having normal cognitive functioning, amnestic MCI, or nonamnestic MCI. Results showed that the relationship between insulin and diagnostic category is moderated by sex, such that men with nonamnestic or amnestic MCI have higher fasting plasma insulin than cognitively normal men, while women with amnestic MCI have lower fasting plasma insulin than cognitively normal women. Exploratory analyses suggest that APOE epsilon 4 genotype may further influence the relationship between sex and insulin. Future research will help determine whether insulin dysregulation results in differential effects on vascular function and AD pathology as a function of sex and/or APOE genotype. C1 [Cholerton, Brenna; Baker, Laura D.; Trittschuh, Emily H.; Arbuckle, Matthew; Saucedo, Hector Hernandez; Craft, Suzanne] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Baker, Laura D.; Trittschuh, Emily H.; Craft, Suzanne] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Crane, Paul K.; Larson, Eric B.; McCormick, Wayne C.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Bowen, James D.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. [McCurry, Susan M.] Univ Washington, Sch Med, Dept Psychosocial & Community Hlth, Seattle, WA USA. [Larson, Eric B.] Grp Hlth Res Inst, Seattle, WA USA. [Bowen, James D.] Swedish Med Ctr, Swedish Neurosci Inst, Seattle, WA USA. RP Cholerton, B (reprint author), VA Puget Sound Hlth Care Syst, GRECC A 182,9600 Vet Dr SW, Tacoma, WA 98493 USA. EM bchol@u.washington.edu RI Crane, Paul/C-8623-2014; OI Crane, Paul/0000-0003-4278-7465 FU National Institute on Aging [R01AG024180, U01AG006781]; Department of Veterans Affairs; Group Health Research Institute FX This research was supported by National Institute on Aging grants R01AG024180 and U01AG006781, the Department of Veterans Affairs, and the Group Health Research Institute. The funding sources did not provide scientific input for the study. NR 67 TC 5 Z9 5 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2012 VL 31 IS 2 BP 401 EP 410 DI 10.3233/JAD-2012-120202 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 986WS UT WOS:000307377300015 PM 22571978 ER PT J AU Kulke, M O'Dorisio, T Phan, A Bergsland, E Freiman, J Law, L Banks, P Frazier, K Jackson, J Zambrowicz, B AF Kulke, M. O'Dorisio, T. Phan, A. Bergsland, E. Freiman, J. Law, L. Banks, P. Frazier, K. Jackson, J. Zambrowicz, B. TI Efficacy of Telotristat Etiprate in Refractory Carcinoid Syndrome: Results of a Randomized, Placebo-controlled, Multicenter Study SO NEUROENDOCRINOLOGY LA English DT Meeting Abstract CT 9th Annual European-Neuroendocrine-Tumor-Society (ENETS) Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease CY MAR 07-09, 2012 CL Copenhagen, DENMARK SP European Neuroendocrine Tumor Soc (ENETS) DE carcinoid syndrome; telotristat etiprate C1 [Kulke, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Dorisio, T.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. [Phan, A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bergsland, E.] Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. [Freiman, J.; Law, L.; Banks, P.; Frazier, K.; Jackson, J.; Zambrowicz, B.] Lexicon Pharmaceut Inc, The Woodlands, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PY 2012 VL 96 SU 1 BP 43 EP 43 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 997AD UT WOS:000308135300122 ER PT J AU Zhu, L Guo, N Li, QZ Ma, Y Jacboson, O Lee, S Choi, HS Mansfield, JR Niu, G Chen, XY AF Zhu, Lei Guo, Ning Li, Quanzheng Ma, Ying Jacboson, Orit Lee, Seulki Choi, Hak Soo Mansfield, James R. Niu, Gang Chen, Xiaoyuan TI Dynamic PET and Optical Imaging and Compartment Modeling using a Dual-labeled Cyclic RGD Peptide Probe SO THERANOSTICS LA English DT Article DE dual modality imaging; dynamic imaging; kinetic modeling; Singular value decomposition (SVD); integrin alpha(v)beta(3); RGD peptide ID POSITRON-EMISSION-TOMOGRAPHY; SMALL-ANIMAL PET; IN-VIVO; ALPHA(V)BETA(3)-INTEGRIN EXPRESSION; TUMOR ANGIOGENESIS; GRAPHICAL ANALYSIS; INTEGRIN; LIMITATIONS; THERAPY; TARGET AB Purpose: The aim of this study is to determine if dynamic optical imaging could provide comparable kinetic parameters to that of dynamic PET imaging by a near-infrared dye/Cu-64 dual-labeled cyclic RGD peptide. Methods: The integrin alpha(v)beta(3) binding RGD peptide was conjugated with a macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for copper labeling and PET imaging and a near-infrared dye ZW-1 for optical imaging. The in vitro biological activity of RGD-C(DOTA)-ZW-1 was characterized by cell staining and receptor binding assay. Sixty-min dynamic PET and optical imaging were acquired on a MDA-MB-435 tumor model. Singular value decomposition (SVD) method was applied to compute the dynamic optical signal from the two-dimensional optical projection images. Compartment models were used to quantitatively analyze and compare the dynamic optical and PET data. Results: The dual-labeled probe Cu-64-RGD-C(DOTA)-ZW-1 showed integrin specific binding in vitro and in vivo. The binding potential (Bp) derived from dynamic optical imaging (1.762 +/- 0.020) is comparable to that from dynamic PET (1.752 +/- 0.026). Conclusion: The signal un-mixing process using SVD improved the accuracy of kinetic modeling of 2D dynamic optical data. Our results demonstrate that 2D dynamic optical imaging with SVD analysis could achieve comparable quantitative results as dynamic PET imaging in preclinical xenograft models. C1 [Zhu, Lei; Guo, Ning; Ma, Ying; Jacboson, Orit; Lee, Seulki; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Zhu, Lei] Xiamen Univ, Ctr Mol Imaging & Translat Med, Xiamen 361005, Fujian, Peoples R China. [Guo, Ning] Huazhong Univ Sci & Technol, Dept Biomed Engn, Wuhan 430074, Hubei, Peoples R China. [Li, Quanzheng] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. [Choi, Hak Soo] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Choi, Hak Soo] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Mansfield, James R.] Caliper Life Sci Inc, Hopkinton, MA 01748 USA. RP Niu, G (reprint author), NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. EM gang.niu@nih.gov; shawn.chen@nih.gov RI Choi, Hak Soo/C-9954-2011; Zhu, Lei/P-9786-2016 OI Zhu, Lei/0000-0002-1820-4795 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); NIH Pathway to Independence Award [K99/R00] FX This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). S. L. is partially supported by an NIH Pathway to Independence (K99/R00) Award. NR 41 TC 15 Z9 15 U1 0 U2 18 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2012 VL 2 IS 8 BP 746 EP 756 DI 10.7150/thno.4762 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 990RK UT WOS:000307648500001 PM 22916074 ER PT J AU Gurses, AP Martinez, EA Bauer, L Kim, G Lubomski, LH Marsteller, JA Pennathur, PR Goeschel, C Pronovost, PJ Thompson, D AF Gurses, Ayse P. Martinez, Elizabeth A. Bauer, Laura Kim, George Lubomski, Lisa H. Marsteller, Jill A. Pennathur, Priyadarshini R. Goeschel, Chris Pronovost, Peter J. Thompson, David TI Using human factors engineering to improve patient safety in the cardiovascular operating room SO WORK-A JOURNAL OF PREVENTION ASSESSMENT & REHABILITATION LA English DT Article DE Safety; Cardiac surgery; Medical error; Human factors ID ADVERSE EVENTS; SURGERY; ERRORS AB Despite significant medical advances, cardiac surgery remains a high risk procedure. Sub-optimal work system design characteristics can contribute to the risks associated with cardiac surgery. However, hazards due to work system characteristics have not been identified in the cardiovascular operating room (CVOR) in sufficient detail to guide improvement efforts. The purpose of this study was to identify and categorize hazards (anything that has the potential to cause a preventable adverse patient safety event) in the CVOR. An interdisciplinary research team used prospective hazard identification methods including direct observations, contextual inquiry, and photographing to collect data in 5 hospitals for a total 22 cardiac surgeries. We performed thematic analysis of the qualitative data guided by a work system model. 60 categories of hazards such as practice variations, high workload, non-compliance with evidence-based guidelines, not including clinicians' in medical device purchasing decisions were found. Results indicated that hazards are common in cardiac surgery and should be eliminated or mitigated to improve patient safety. To improve patient safety in the CVOR, efforts should focus on creating a culture of safety, increasing compliance with evidence based infection control practices, improving communication and teamwork, and designing better tools and technologies through partnership among all stakeholders. C1 [Gurses, Ayse P.; Bauer, Laura; Lubomski, Lisa H.; Marsteller, Jill A.; Pennathur, Priyadarshini R.; Goeschel, Chris; Pronovost, Peter J.; Thompson, David] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Gurses, Ayse P.; Kim, George] Johns Hopkins Univ, Sch Med, Div Hlth Sci Informat, Baltimore, MD 21205 USA. [Gurses, Ayse P.; Marsteller, Jill A.; Goeschel, Chris; Pronovost, Peter J.] Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. [Martinez, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Goeschel, Chris; Pronovost, Peter J.; Thompson, David] Johns Hopkins Sch Nursing, Baltimore, MD USA. RP Gurses, AP (reprint author), Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. EM agurses1@jhmi.edu FU AHRQ HHS [K01 HS018762, K08 HS013904-02] NR 10 TC 5 Z9 6 U1 0 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1051-9815 EI 1875-9270 J9 WORK JI Work PY 2012 VL 41 SU 1 BP 1801 EP 1804 DI 10.3233/WOR-2012-0388-1801 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 973LO UT WOS:000306361801143 PM 22316975 ER PT J AU Towsley, G Neradilek, MB Snow, AL Ersek, M AF Towsley, Gail Neradilek, Moni Blazej Snow, A. Lynn Ersek, Mary TI Evaluating the Cornell scale for depression in dementia as a proxy measure in nursing home residents with and without dementia SO AGING & MENTAL HEALTH LA English DT Article DE depression; proxy measure; nursing homes; dementia ID QUALITY-OF-LIFE; LONG-TERM-CARE; ALZHEIMERS-DISEASE; MAJOR DEPRESSION; OLDER-PEOPLE; SYMPTOMS; MANAGEMENT; PAIN; PREVALENCE; VALIDITY AB Objectives: We evaluated the use of the Cornell Scale for Depression in Dementia (CSDD) as a proxy measure. Study questions were: How do residents' self-reports on the CSDD compare with the nurse proxy CSDD ratings of the resident? How do characteristics of depression as rated by the resident CSDD and the nurse CSDD compare? To what extent are demographic and clinical variables associated with resident CSDD, nurse CSDD, and the discrepancy between resident and nurse CSDD scores? Methods: Residents and nurse proxy pairs (n = 395 pairs) from 28 nursing homes (NHs) participated. We calculated discrepancy scores for total and subscale CSDD scores, examined correlations between resident and nurse CSDD scores, and described rates of clinical depression using each of the scores. We conducted multivariate analyses to examine factors associated with resident and nurse CSDD and discrepancy scores. Results: On average, participants had mild cognitive impairment, were White, and female. Associations between resident and nurse CSDD were low (r = 0.16). The mean discrepancy score was -2.03 (SD = 5.28, p < 0.001), indicating that nurses evaluated residents as less depressed than residents evaluated themselves. Discrepancy scores were not associated with residents' cognitive status, but were associated with a measure of self-report reliability. Regression analyses indicated that depression diagnosis accounted for a small but significant association with resident CSDD, but was not significantly associated with nurse CSDD. Conclusion: These findings underscore the importance of obtaining resident input when assessing depression in NH residents with dementia, and educating NH nurses in the most effective ways to assess depression. C1 [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Towsley, Gail] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Neradilek, Moni Blazej] Mt Whisper Light Stat Consulting, Seattle, WA USA. [Snow, A. Lynn] Univ Alabama, Ctr Mental Hlth & Aging, Tuscaloosa, AL USA. [Snow, A. Lynn] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA. [Ersek, Mary] Philadelphia Vet Affairs Med Ctr, Natl VA PROMISE Ctr, Philadelphia, PA USA. RP Ersek, M (reprint author), Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. EM ersekm@nursing.upenn.edu FU National Institute of Nursing Research [R01NR009100] FX This study was supported by Award Number R01NR009100 from the National Institute of Nursing Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Nursing Research or the National Institutes of Health. NR 40 TC 6 Z9 6 U1 3 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PY 2012 VL 16 IS 7 BP 892 EP 901 DI 10.1080/13607863.2012.667785 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 987TI UT WOS:000307440200011 PM 22486638 ER PT J AU Tucker, JD Walensky, RP Yang, LG Yang, B Bangsberg, DR Chen, XS Cohen, MS AF Tucker, Joseph D. Walensky, Rochelle P. Yang, Li-Gang Yang, Bin Bangsberg, David R. Chen, Xiang-Sheng Cohen, Myron S. TI Expanding provider-initiated HIV testing at STI clinics in China SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; STI; physician; China; implementation ID TRANSMITTED-DISEASE CLINICS; CARE; PROFESSIONALS; PHYSICIANS; INFECTION AB Despite expanding sexually transmitted epidemics in South China, the majority of patients presenting to sexually transmitted infection (STI) clinics are not routinely screened for HIV infection. Identifying barriers to offering HIV testing among STI care providers is an important public health priority. The aim of this study was to investigate the frequency of offering HIV testing among STI care providers in South China and reported physician barriers to offering HIV testing. More detailed operational data regarding HIV test offer frequency and barriers to testing may enhance routine HIV testing at STI clinics. A sample of 62 STI care providers within the Pearl River Delta Region of South China completed a survey including socio-demographic and training background information (including sex, age, medical education, year of terminal medical degree, and HIV-specific training), reasons for not offering HIV testing routinely, and physical examination and sexual history taking practices. Frequency of offering HIV testing was calculated based on reports from research assistants and operational data. STI care providers offered HIV testing to 3011/10,592 (28.4%) of their patients. There was substantial variability across providers in the frequency of offering testing, ranging from 3 to 100%. None of the identified physician factors were associated with offering HIV testing 100% of the time in the multivariate model. The most commonly physician reported barriers to HIV testing included: (1) low perceived prevalence of disease and (2) not recommended by current guidelines. Forty-seven providers (76%) reported asking about same sex behaviors rarely or never. Further research on HIV screening practices of STI care providers may help scale up HIV provider-initiated testing and counseling programs. C1 [Tucker, Joseph D.] Guangdong Prov Ctr Skin Dis & STD Control, STD Control Dept, Guangzhou, Peoples R China. [Tucker, Joseph D.; Walensky, Rochelle P.; Bangsberg, David R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Tucker, Joseph D.; Yang, Li-Gang; Yang, Bin; Cohen, Myron S.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA. [Chen, Xiang-Sheng] Chinese Acad Med Sci, Natl Ctr STD Control, Nanjing, Peoples R China. [Chen, Xiang-Sheng] Peking Union Med Coll, Inst Dermatol, Nanjing, Peoples R China. RP Tucker, JD (reprint author), Guangdong Prov Ctr Skin Dis & STD Control, STD Control Dept, Guangzhou, Peoples R China. EM jtucker4@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU FIC NIH HHS [D43 TW001039, 1K01TW008200-01A1, D43 TW01039, K01 TW008200]; NIAID NIH HHS [P30 AI050410]; NICHD NIH HHS [R24 HD056670, R24 HD056670-01]; NIMH NIH HHS [K24 MH087227] NR 20 TC 0 Z9 0 U1 0 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2012 VL 24 IS 10 BP 1316 EP 1319 DI 10.1080/09540121.2012.661835 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 976PM UT WOS:000306596800017 PM 22512378 ER PT J AU Fallows, RR Hilsabeck, RC AF Fallows, Robert R. Hilsabeck, Robin C. TI WAIS-IV Visual Puzzles in a Mixed Clinical Sample SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Visual puzzles; WAIS-IV; Visuospatial; Perceptual reasoning; Intelligence ID FORM-BOARD TEST; SPATIAL ABILITY; SEX-DIFFERENCES; BATTERY; SCORES; TESTS AB Little is known about which cognitive functions underlie the new Visual Puzzles subtest of the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV). The purpose of this study was to investigate relationships between Visual Puzzles and common neuropsychological measures in a mixed clinical sample. A total of 44 veterans (75% men) were administered the WAIS-IV as part of a neuropsychological evaluation. Average age was 47.4 years (SD = 11.8), and average education was 13.8 years (SD = 2.3). Correlations were conducted to examine relationships between Visual Puzzles, demographic variables, and neuropsychological measures. Hierarchical regression analysis was used to determine which measures contributed the most variance to Visual Puzzles. Visual Puzzles correlated significantly with measures of visuospatial reasoning, verbal learning and recall, mental flexibility, processing speed, and naming, which accounted for 50% of the variance in Visual Puzzles performance. The results indicate that Visual Puzzles is not a pure measure of visuoperceptual reasoning, at least in a mixed clinical sample, because memory, mental flexibility, processing speed, and language abilities also contribute to successful performance of the task. Thus it may be important to consider other aspects of cognitive functioning when interpreting Visual Puzzles performance. C1 [Fallows, Robert R.; Hilsabeck, Robin C.] S Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX 78229 USA. [Hilsabeck, Robin C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Hilsabeck, RC (reprint author), S Texas Vet Hlth Care Syst, Psychol Serv 116B, 7400 Merton Minter, San Antonio, TX 78229 USA. EM Robin.Hilsabeck@va.gov NR 26 TC 3 Z9 3 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2012 VL 26 IS 6 BP 942 EP 950 DI 10.1080/13854046.2012.697193 PG 9 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 984ZK UT WOS:000307232300006 PM 22694190 ER PT J AU Kiewel, NA Wisdom, NM Bradshaw, MR Pastorek, NJ Strutt, AM AF Kiewel, Nicole A. Wisdom, Nick M. Bradshaw, Major R. Pastorek, Nicholas J. Strutt, Adriana M. TI A Retrospective Review of Digit Span-Related Effort Indicators in Probable Alzheimer's Disease Patients SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Malingering; Symptom validity testing; Forensic neuropsychology; Dementia assessment; Professional issues ID SYMPTOM VALIDITY TEST; MALINGERED NEUROCOGNITIVE DYSFUNCTION; TRAUMATIC BRAIN-INJURY; CLASSIFICATION ACCURACY; MEMORY IMPAIRMENT; TEST-PERFORMANCE; WAIS-III; COGNITIVELY INTACT; NORMATIVE DATA; TEST-SCORES AB There has been extensive research on the use of both stand-alone and embedded measures of effort in neuropsychological testing; however, relatively few studies have reported on their utility in the context of dementia. Previous studies that have examined the specificity of traditionally used cut-scores on embedded measures of effort with dementia samples have largely found high rates of false positive errors. The present study examined the specificity of several Digit Span derived embedded measures of effort in a large clinical sample of patients with probable Alzheimer's disease stratified by level of dementia severity. Of the measures that were examined, only the Vocabulary - Digit Span score demonstrated promising specificity through the moderate level of dementia severity. All of the remaining indices, including Reliable Digit Span, Digit Span Age-Corrected Scaled Score, and Longest Digits Forward (1 & 2 Trials), yielded unacceptable rates of false positive errors as dementia severity increased. The implications for these findings are discussed, including the limitations of importing methods of assessing effort from one sample to another. C1 [Bradshaw, Major R.; Strutt, Adriana M.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Kiewel, Nicole A.] Univ Houston, Dept Psychol, Houston, TX USA. [Wisdom, Nick M.] Mental Hlth Care Line, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Wisdom, Nick M.; Strutt, Adriana M.] Baylor Coll Med, Menninger Dept Psychiat, Houston, TX 77030 USA. [Pastorek, Nicholas J.] Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. [Pastorek, Nicholas J.] Rehabil Care Line, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Strutt, AM (reprint author), Baylor Coll Med, Dept Neurol, 6550 Fannin,Smith Tower 1801, Houston, TX 77030 USA. EM adrianam@bcm.edu NR 35 TC 2 Z9 3 U1 1 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1385-4046 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2012 VL 26 IS 6 BP 965 EP 974 DI 10.1080/13854046.2012.694478 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 984ZK UT WOS:000307232300008 PM 22703555 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Doctored: The Medicine of Photography in Nineteenth-Century America SO HISTORY OF PHOTOGRAPHY LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0308-7298 EI 2150-7295 J9 HIST PHOTOGR JI Hist. Photogr. PY 2012 VL 36 IS 3 BP 376 EP 377 DI 10.1080/03087298.2012.688369 PG 3 WC Art SC Art GA 971RU UT WOS:000306222300018 ER PT J AU Rellini, AH Vujanovic, AA Gilbert, M Zvolensky, MJ AF Rellini, Alessandra H. Vujanovic, Anka A. Gilbert, Myani Zvolensky, Michael J. TI Childhood Maltreatment and Difficulties in Emotion Regulation: Associations with Sexual and Relationship Satisfaction among Young Adult Women SO JOURNAL OF SEX RESEARCH LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; EMPIRICAL LITERATURE; COMMUNITY SAMPLE; ABUSE; HISTORY; DYSREGULATION; DYSFUNCTION; VALIDATION; NEGLECT; COUPLES AB This study examined relations among childhood maltreatment, difficulties in emotion regulation, and sexual and relationship satisfaction among young adult women reporting current involvement in committed, romantic relationships. A sample of 192 women (ages 18-25) completed self-report questionnaires as part of an Internet-based survey. It was hypothesized that severity of childhood maltreatment and difficulties in emotion regulation would each independently and negatively predict (a) sexual satisfaction, (b) relationship intimacy, and (c) expression of affection within the context of the relationship. Furthermore, it was hypothesized that greater emotion regulation difficulties would moderate the effects of childhood maltreatment on these sexual and relationship variables (i.e., sexual satisfaction, relationship intimacy, and expression of affection). Findings suggest that difficulties in emotion regulation demonstrated an incremental effect with regard to sexual satisfaction, but not with intimacy and affection expression. In contrast to predictions, no significant interactive effects were documented. Clinical implications and future directions related to this line of inquiry are discussed. C1 [Rellini, Alessandra H.; Gilbert, Myani; Zvolensky, Michael J.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Vujanovic, Anka A.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD,Behav Sci Div, Boston, MA 02215 USA. RP Rellini, AH (reprint author), Univ Vermont, Dept Psychol, John Dewey Hall,2 Colchester Ave, Burlington, VT 05405 USA. EM arellini@uvm.edu NR 42 TC 9 Z9 9 U1 3 U2 27 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0022-4499 J9 J SEX RES JI J. Sex Res. PY 2012 VL 49 IS 5 BP 434 EP 442 DI 10.1080/00224499.2011.565430 PG 9 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 984ZQ UT WOS:000307232900003 PM 21512946 ER PT J AU Tilford, JM Payakachat, N Kovacs, E Pyne, JM Brouwer, W Nick, TG Bellando, J Kuhlthau, KA AF Tilford, J. Mick Payakachat, Nalin Kovacs, Erica Pyne, Jeffrey M. Brouwer, Werner Nick, Todd G. Bellando, Jayne Kuhlthau, Karen A. TI Preference-Based Health-Related Quality-of-Life Outcomes in Children with Autism Spectrum Disorders A Comparison of Generic Instruments SO PHARMACOECONOMICS LA English DT Article ID COST-EFFECTIVENESS ANALYSIS; WELL-BEING SCALE; UTILITY SCORES; CLINICAL-TRIALS; CYSTIC-FIBROSIS; SLEEP PROBLEMS; SF-6D; EQ-5D; HUI3; CARE AB Background: Cost-effectiveness analysis of pharmaceutical and other treatments for children with autism spectrum disorders (ASDs) has the potential to improve access to services by demonstrating the value of treatment to public and private payers, but methods for measuring QALYs in children are under-studied. No cost-effectiveness analyses have been undertaken in this population using the cost-per-QALY metric. Objective: This study describes health-related quality-of-life (HR-QOL) outcomes in children with ASDs and compares the sensitivity of two generic preference-based instruments relative to ASD-related conditions and symptoms. Methods: The study design was cross-sectional with prospectively collected outcome data that were correlated with retrospectively assessed clinical information. Subjects were recruited from two sites of the Autism Treatment Network (ATN) in the US: a developmental centre in Little Rock, Arkansas, and an outpatient psychiatric clinic at Columbia University Medical Center in New York. Children that met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for an ASD by a multidisciplinary team evaluation were asked to participate in a clinical registry. Families of children with an ASD that agreed to be contacted about participation in future research studies as part of the ATN formed the sampling frame for the study. Families were included if the child with the ASD was between 4 and 17 years of age and the family caregiver spoke English. Eligible families were contacted by mail to see if they would be interested in participating in the study with 150 completing surveys. HR-QOL outcomes were described using the Health Utilities Index (HUI) 3 and the Quality of Well-Being Self-Administered (QWB-SA) scale obtained by proxy via the family caregiver. Results: Children were diagnosed as having autistic disorder (76%), pervasive developmental disorder-not otherwise specified [PDD-NOS] (15%), and Asperger's disorder (9%). Average HUI3 and QWB-SA scores were 0.68 (SD 0.21, range 0.07-1) and 0.59 (SD 0.16, range 0.18-1), respectively. The HUI3 score was significantly correlated with clinical variables including adaptive behaviour (rho = 0.52; p < 0.001) and cognitive functioning (rho = 0.36; p < 0.001). The QWB-SA score had weak correlation with adaptive behaviour (rho = 0.25; p < 0.001) and cognitive functioning (rho = 0.17; p < 0.005). Change scores for the HUI3 were larger than the QWB-SA for all clinical measures. Scores for the HUI3 increased 0.21 points (95% CI 0.14, 0.29) across the first to the third quartile of the cognitive functioning measure compared with 0.05 (95% CI -0.01, 0.11) for the QWB-SA. Adjusted R-2 values also were higher for the HUI3 compared with the QWB-SA across all clinical measures. Conclusions: The HUI3 was more sensitive to clinical measures used to characterize children with autism compared with the QWB-SA score. The findings provide a benchmark to compare scores obtained by alternative methods and instruments. Researchers should consider incorporating the HUI3 in clinical trials and other longitudinal research studies to build the evidence base for describing the cost effectiveness of services provided to this important population. C1 [Tilford, J. Mick] Univ Arkansas Med Sci, Dept Hlth Policy & Management, Little Rock, AR 72205 USA. [Tilford, J. Mick; Payakachat, Nalin] Univ Arkansas Med Sci, Dept Pharm Practice, Little Rock, AR 72205 USA. [Tilford, J. Mick; Nick, Todd G.; Bellando, Jayne] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Kovacs, Erica] Columbia Univ, Dept Psychiat, Med Ctr, New York, NY USA. [Pyne, Jeffrey M.] Cent Arkansas Vet Healthcare Syst, Ctr Mental Healthcare & Outcomes Res, Little Rock, AR USA. [Pyne, Jeffrey M.] Univ Arkansas Med Sci, Inst Psychiat Res, Little Rock, AR 72205 USA. [Brouwer, Werner] Erasmus Univ, Dept Hlth Policy & Management, Rotterdam, Netherlands. [Kuhlthau, Karen A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Kuhlthau, Karen A.] Massachusetts Gen Hosp, Ctr Adolescent Hlth Policy, Boston, MA 02114 USA. RP Tilford, JM (reprint author), Univ Arkansas Med Sci, Dept Hlth Policy & Management, 4301 W Markham St,Slot 820, Little Rock, AR 72205 USA. EM tilfordmickj@uams.edu FU National Institute of Mental Health [R01MH089466]; U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC 11054] FX The project was supported by a grant (no. R01MH089466) from the National Institute of Mental Health with JMT and KAK serving as principal investigators. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. The authors acknowledge the members of the ATN for use of the data. The data for the study were collected as part of the ATN, a programme of Autism Speaks. Further support came from a cooperative agreement (UA3 MC 11054) from the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program, to the Massachusetts General Hospital. The work described in this article represents the independent efforts of the authors with no restrictions from the funding source or the ATN. None of the authors of this study reported a conflict of interest associated with the preparation of the manuscript. Maria Melguizo, Nupur Chowdhury, Rebecca Rieger and Latunja Sockwell provided excellent research assistance. NR 62 TC 20 Z9 21 U1 2 U2 22 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 1170-7690 EI 1179-2027 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2012 VL 30 IS 8 BP 661 EP 679 PG 19 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 982HI UT WOS:000307033300004 PM 22788258 ER PT J AU Peretti, CS Peretti, CR Kozora, E Papathanassiou, D Chouinard, VA Chouinard, G AF Peretti, Charles-Siegfried Peretti, Charles Roger Kozora, Elizabeth Papathanassiou, Dimitri Chouinard, Virginie-Anne Chouinard, Guy TI Cognitive Impairment in Systemic Lupus Erythematosus Women with Elevated Autoantibodies and Normal Single Photon Emission Computerized Tomography SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE Systemic lupus erythematosus; Neuropsychiatric SLE; Non-neuropsychiatric SLE; Cognitive impairment in SLE; Cognitive dysfunction in SLE; SLE autoantibodies; SPECT in SLE; Caucasian SLE women ID CEREBRAL-BLOOD-FLOW; PSYCHIATRIC-SYMPTOMS; GLUCOSE-METABOLISM; NMDA RECEPTORS; BRAIN SPECT; MEMORY; DEPRESSION; ANTIBODIES; STRESS; AGE AB Background: Systemic lupus erythematosus (SLE) is known to induce psychiatric disorders, from psychoses to maladaptive coping. Brain autoantibodies were proposed to explain SLE neuropsychiatric disorders and found to be elevated before the onset of clinical symptoms. We assessed cognition in Caucasian SLE women with elevated autoantibodies without overt neuropsychiatric syndromes, in conjunction with single photon emission computerized tomography ( SPECT). Methods: 31 women meeting SLE criteria of the American College of Rheumatology (ACR) were included. Patients who met the ACR neuropsychiatric definition were excluded. Matched controls were 23 healthy women from the Champagne-Ardenne region, France. Participants completed neuropsychological and autoantibodies measurements, and 19 completed SPECT. Results: 61% (19/31) of women with SLE and 53% (9/17) of those with normal SPECT had significant global cognitive impairment defined as 4 T-scores <40 in cognitive tests, compared to 0% ( 0/23) of controls. SLE women also had significantly greater cognitive dysfunction ( mean T-score) on the Wechsler Adult Intelligence Scale (WAIS) visual backspan, Trail Making Test A and B, WAIS Digit Symbol Substitution Test and Stroop Interference, compared to controls. Elevated antinuclear antibody correlated with impairment in the WAIS visual span, WAIS visual backspan, and cancellation task; elevated anti-double-stranded DNA antibody and anticardiolipin correlated respectively with impairment in the Trail Making Test A and WAIS auditive backspan. Two SLE women had abnormal SPECT. Conclusions: A high prevalence of cognitive deficits was found in Caucasian SLE women compared to normal women, which included impairment in cognitive domains important for daily activities. Elevated autoantibodies tended to correlate with cognitive dysfunction. Copyright (c) 2012 S. Karger AG, Basel C1 [Peretti, Charles-Siegfried] St Antoine Hosp, Dept Psychiat, FR-75012 Paris, France. [Peretti, Charles-Siegfried] Univ Paris 06, Dept Psychiat, Paris, France. [Peretti, Charles Roger] Univ Paris 06, Dept Phys, Paris, France. [Papathanassiou, Dimitri] Inst Jean Godinoi, Nucl Med Serv, F-51056 Reims, France. [Kozora, Elizabeth] Univ Colorado, Denver Sch Med, Natl Jewish Hlth, Denver, CO 80202 USA. [Chouinard, Virginie-Anne] Harvard Univ, Massachusetts Gen Hosp, Sch Med, McLean Adult Psychiat Residency Training Program, Boston, MA USA. [Chouinard, Guy] McGill Univ, McGill Univ Hosp Ctr, Dept Psychiat, Montreal, PQ, Canada. [Chouinard, Guy] McGill Univ, McGill Univ Hosp Ctr, Dept Med, Montreal, PQ, Canada. RP Peretti, CS (reprint author), St Antoine Hosp, Dept Psychiat, Batiment Robert Andre 184,Rue Faubourg St Antoine, FR-75012 Paris, France. EM charles.peretti@sat.aphp.fr FU Servier; Schering Plough; Lilly; Pfizer; UCB; Eisai; BMS; Sanofi-Aventis; National Jewish Health FX Prof. C.S. Peretti reported receiving research support and honoraria from Servier, Schering Plough, Lilly, Pfizer, UCB, Eisai, BMS, Sanofi-Aventis. Prof. G. Chouinard received honoraria for consultancy from Takeda, and owns shares of Pfizer. Dr. E. Kozora reported receiving support for consultancy from hospital for special surgery and salary support from the National Jewish Health. The other authors report no financial relationships with commercial interests. NR 47 TC 7 Z9 9 U1 2 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2012 VL 81 IS 5 BP 276 EP 285 DI 10.1159/000336555 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 986WN UT WOS:000307376700002 PM 22832425 ER PT J AU Kelley, JM Kaptchuk, TJ Cusin, C Lipkin, S Fava, M AF Kelley, John M. Kaptchuk, Ted J. Cusin, Cristina Lipkin, Samuel Fava, Maurizio TI Open-Label Placebo for Major Depressive Disorder: A Pilot Randomized Controlled Trial SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Letter C1 [Kelley, John M.] Endicott Coll, Dept Psychol, Beverly, MA 01915 USA. [Kelley, John M.; Kaptchuk, Ted J.] Beth Israel Deaconess Med Ctr, Program Placebo Studies, Boston, MA 02215 USA. [Kelley, John M.; Kaptchuk, Ted J.; Cusin, Cristina; Lipkin, Samuel; Fava, Maurizio] Harvard Univ, Sch Med, Boston, MA USA. [Kelley, John M.; Cusin, Cristina; Lipkin, Samuel; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. RP Kelley, JM (reprint author), Endicott Coll, Dept Psychol, 376 Hale St, Beverly, MA 01915 USA. EM johnkelley@post.harvard.edu FU NCCIH NIH HHS [K24 AT004095] NR 10 TC 25 Z9 25 U1 2 U2 14 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2012 VL 81 IS 5 BP 312 EP 314 DI 10.1159/000337053 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 986WN UT WOS:000307376700006 PM 22854752 ER PT J AU Manzano-Fernandez, S Januzzi, JL Pastor-Perez, FJ Bonaque-Gonzalez, JC Boronat-Garcia, M Pascual-Figal, DA Montalban-Larrea, S Navarro-Penalver, M Andreu-Cayuelas, JM Valdes, M AF Manzano-Fernandez, S. Januzzi, J. L. Pastor-Perez, F. J. Bonaque-Gonzalez, J. C. Boronat-Garcia, M. Pascual-Figal, D. A. Montalban-Larrea, S. Navarro-Penalver, M. Andreu-Cayuelas, J. M. Valdes, M. TI Serial Monitoring of Soluble Interleukin Family Member ST2 in Patients with Acutely Decompensated Heart Failure SO CARDIOLOGY LA English DT Article DE ST2; Monitoring; Prognosis; Heart failure ID PRESERVED EJECTION FRACTION; BRAIN NATRIURETIC PEPTIDE; CARDIAC TROPONIN; RISK STRATIFICATION; MYOCARDIAL-INFARCTION; ACUTE DYSPNEA; MORTALITY; DIAGNOSIS; RECEPTOR; PLASMA AB Objectives: To determine whether serial measures of the interleukin receptor family member soluble ST2 (sST2) provide additional prognostic information to baseline measures for long-term risk stratification of acutely decompensated heart failure (ADHF) patients. Methods: We prospectively enrolled 72 ADHF patients. Blood samples were collected to measure sST2 concentrations at presentation and on day 4 of hospitalization. All patients were clinically followed, and vital status was registered. Results: Between presentation and day 4, sST2 concentrations decreased from 62 ng/ml (interquartile range 38-105) to 44 ng/ml (interquartile range 26-72; p < 0.001). Both sST2 concentrations at presentation [hazard ratio (HR) 1.011, 95% confidence interval (CI) 1.005-1.016; p < 0.001] and on day 4 (HR 1.015, 95% CI 1.005-1.024; p = 0.003) were independent predictors of mortality. Patients with sST2 <= 76 ng/ml at presentation and <= 46 ng/ml on day 4 had the lowest mortality rates (3%), whereas those with both sST2 values above these cutoff points had the highest mortality (50%). C index and reclassification analyses demonstrated that the use of serial sST2 measures resulted in an improvement in the accuracy of mortality prediction. Conclusions: Among ADHF patients, sST2 concentrations tend to decrease following initiation of treatment and are prognostic both at presentation and during hospitalization. Serial sampling of sST2 adds prognostic information and may provide a basis for enhanced clinical decision making. Copyright (C) 2012 S. Karger AG, Basel C1 [Manzano-Fernandez, S.; Pastor-Perez, F. J.; Bonaque-Gonzalez, J. C.; Pascual-Figal, D. A.; Montalban-Larrea, S.; Navarro-Penalver, M.; Andreu-Cayuelas, J. M.; Valdes, M.] Univ Hosp Virgen de la Arrixaca, Dept Cardiol, ES-30120 Murcia, Spain. [Boronat-Garcia, M.] Univ Hosp Virgen de la Arrixaca, Dept Biochem, ES-30120 Murcia, Spain. [Januzzi, J. L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Manzano-Fernandez, S (reprint author), Univ Hosp Virgen de la Arrixaca, Dept Cardiol, C Madrid Cartagena S-N, ES-30120 Murcia, Spain. EM sergiosmf13@hotmail.com RI Pascual Figal, Domingo /B-3794-2008; OI Pascual Figal, Domingo /0000-0002-4993-9540; Andreu-Cayuelas, Jose Manuel/0000-0002-0535-572X FU Roche Diagnostics; Siemens; Critical Diagnostics FX Dr. Januzzi reports receiving grant support from Roche Diagnostics, Siemens and Critical Diagnostics. Dr. Pascual-Figal reports receiving grant support from Roche Diagnostics. Otherwise, no potential conflicts of interest exist. NR 34 TC 27 Z9 30 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2012 VL 122 IS 3 BP 158 EP 166 DI 10.1159/000338800 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 986WF UT WOS:000307375700004 PM 22832599 ER PT J AU Resnik, L Reiber, G AF Resnik, Linda Reiber, Gayle TI Long-term Disabilities Associated With Combat Casualties: Measuring Disability and Reintegration in Combat Veterans SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID TRAUMATIC BRAIN-INJURY; INTERNATIONAL CLASSIFICATION; COMMUNITY REINTEGRATION; HEALTH; PARTICIPATION; SERVICEMEMBERS; OUTCOMES AB Many physical and mental health problems associated with combat casualties affect the reintegration of service members into home and community life. Quantifying and measuring reintegration is important to answer questions about clinical, research, economic, and policy issues that directly affect combat veterans. Although the construct of participation presented in the International Statistical Classification of Diseases and Related Health Problems and in the International Classification of Functioning, Disability and Health provides a theoretical framework with which to understand and measure community reintegration in general, a measure was needed that specifically addressed the reintegration of combat veterans. To address this need, the Community Reintegration for Service Members global outcomes measure was developed. It consists of three scales, which measure extent of participation, perceived limitations, and satisfaction. The measure was validated in a general sample of veterans and in a sample of severely wounded service members. The computer-adapted test version shows good precision, reliability, construct validity, and predictive validity. C1 [Resnik, Linda] Brown Univ, Providence VA Med Ctr, Alpert Med Sch, Providence, RI 02912 USA. [Resnik, Linda] Brown Univ, Dept Hlth Serv Policy & Practice, Alpert Med Sch, Providence, RI 02912 USA. [Reiber, Gayle] Univ Washington, Hlth Serv Res & Dev Serv, Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Reiber, Gayle] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Resnik, L (reprint author), Brown Univ, Providence VA Med Ctr, Alpert Med Sch, Providence, RI 02912 USA. NR 17 TC 4 Z9 4 U1 1 U2 8 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PY 2012 VL 20 SU 1 BP S31 EP S34 DI 10.5435/JAAOS-20-08-S31 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 984NZ UT WOS:000307199000008 PM 22865133 ER PT J AU Jennings, LK Michelson, AD Jacoski, MV Tyagi, A Grgurevich, S Li, JS AF Jennings, Lisa K. Michelson, Alan D. Jacoski, Mary V. Tyagi, Aditya Grgurevich, Svetozar Li, Jennifer S. CA PICOLO Investigators TI Pharmacodynamic effects of clopidogrel in pediatric cardiac patients: A comparative study of platelet aggregation response SO PLATELETS LA English DT Article DE Heart defects; congenital; pediatrics; platelet aggregation; platelet inhibitors ID CORONARY-ARTERY-DISEASE; WHOLE-BLOOD; ASPIRIN RESISTANCE; NEONATAL PLATELETS; RESPONSIVENESS; VARIABILITY; CHILDREN; REACTIVITY; NEWBORNS; INFANTS AB Little data on pediatric percent platelet aggregation (%PA) exist in the literature, particularly in cardiac patients and in response to clopidogrel. The objectives were to estimate the %PA range expected in pediatric patients and to measure the clopidogrel effect on %PA in the PICOLO (Platelet Inhibition in Children on Clopidogrel) trial. To estimate a neonatal/infant %PA response range, %PA induced by 5 mu M adenosine diphosphate (ADP) was assessed using light transmission aggregometry in 16 cord and 11 normal adult blood samples and prior to clopidogrel therapy in 49 neonatal and 49 infant/toddler cardiac patients enrolled in PICOLO. The %PA induced by 5 mu M thrombin receptor-activating peptide (TRAP) was also assessed for 10 neonates and 21 infants/toddlers enrolled in PICOLO and compared with 11 adult samples. Percent inhibition of platelet aggregation (%IPA) induced by 5 mu M ADP at steady-state clopidogrel levels was assessed in 33 neonates and 39 infants/toddlers. ADP-induced %PA was lowest in cord blood samples, intermediate in study neonates and infants/toddlers, and highest in adults. Similarly, TRAP-induced platelet aggregation was lower in neonates and infants/toddlers than adults. For all groups, %PA and %IPA were highly variable, with 11% of neonates and 13% of infants/toddlers showing <10% IPA. In conclusion, ADP-and TRAP-induced %PA is lower in pediatric cardiac patients than normal adults, but highly variable in both. The lower baseline %PA may explain why the pediatric clopidogrel dose providing 30-50% IPA (0.20 mg/kg/day) is lower than a simple weight-based extrapolation of the adult dose (75 mg/day) providing similar inhibition. C1 [Jennings, Lisa K.; Jacoski, Mary V.; Tyagi, Aditya; Grgurevich, Svetozar] Univ Tennessee, Hlth Sci Ctr, Vasc Biol Ctr Excellence, Memphis, TN 38163 USA. [Michelson, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Childrens Hosp Boston, Div Hematol Oncol,Ctr Platelet Res Studies, Boston, MA 02115 USA. [Li, Jennifer S.] Duke Univ, Med Ctr, Dept Pediat, Div Pediat Cardiol, Durham, NC 27710 USA. [Li, Jennifer S.] Duke Clin Res Inst, Durham, NC USA. RP Jennings, LK (reprint author), Univ Tennessee, Hlth Sci Ctr, Vasc Biol Ctr Excellence, Coleman Bldg,Room H300,956 Court Ave, Memphis, TN 38163 USA. EM ljennings@uthsc.edu FU Sanofi; Bristol-Myers Squibb, Inc.; sanofi-aventis; GLSynthesis; Lilly/Daiichi Sankyo; Sanofi/Bristol-Myers Squibb; sanofi-aventis/Bristol-Myers Squibb FX This manuscript was written and edited by the authors, who take full responsibility for its content. Editorial assistance with searching the literature, coordinating revisions, and creating figures and tables in preparation of this manuscript was provided by Melanie Leiby, PhD, of inScience Communications, a Wolters Kluwer business, and funded by Sanofi and Bristol-Myers Squibb, Inc. The PICOLO study and the preliminary platelet aggregation study were sponsored by sanofi-aventis and Bristol-Myers Squibb, Inc.; Alan D. Michelson, MD, has been the principal investigator or coinvestigator on research grants to the University of Massachusetts Medical School, Children's Hospital Boston, or both from GLSynthesis, Lilly/Daiichi Sankyo, and Sanofi/Bristol-Myers Squibb. Dr Michelson was also a member of the Data Safety Monitoring Board of the CLARINET trial (a clinical trial sponsored by sanofi-aventis/Bristol-Myers Squibb) and a consultant to Lilly/Daiichi Sankyo. NR 32 TC 1 Z9 1 U1 2 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0953-7104 J9 PLATELETS JI Platelets PY 2012 VL 23 IS 6 BP 430 EP 438 DI 10.3109/09537104.2011.650244 PG 9 WC Cell Biology; Hematology SC Cell Biology; Hematology GA 983HU UT WOS:000307111200003 PM 22309046 ER EF